UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Published by United Kingdom Haemophilia Centre Doctors’ Organisation 2018
© UKHCDO 2018
Copyright of the United Kingdom Haemophilia Centre Doctors’ Organisation. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any other form by any means, electronic, mechanical, photocopying or otherwise without the prior permission in writing of the Chairman, c/o Secretariat, UKHCDO, City View House, Union Street, Ardwick, Manchester, M12 4JD.
ISBN: 978-1-901787-22-1
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Contents
1. Chairman’s Report 1
2. Bleeding Disorder Statistics for 2017 / 2018 Contents 6
2.0. Comments on the Bleeding Disorder Statistics for 2017 / 2018 12
2.1 Haemophilia A 15
2.2 Haemophilia B 45
2.3 Von Willebrand Disease 57
2.4 Inhibitors Congenital and Acquired 63
2.5 Rarer Bleeding Disorders 69
2.6 Adverse Events 74
2.7 Morbidity and Mortality 76
3. Haemtrack Report 2017 84
4. Data Management Working Party 93
5. Data Analysis Group 96
6. Co-Morbidities Working Party 98
7. Genetics Working Party 99
8. Genetic Laboratory Network 101
9. Inhibitor Working Party 103
10. Laboratory Working Party 105
11. Musculoskeletal Working Party 107
12. Paediatric Working Party 108
13. Von Willebrand Working Party 110
14. Peer Review Working Party 111
15. Gynaecology Task Force 112
16. Prophylaxis Task Force 113
17. Haemophilia Nurses’ Association 114
18. Haemophilia Chartered Physiotherapists' Association 116
19. BCSH Haemostasis and Thrombosis Task Force 118
20. Haemophilia Society 121
21. Macfarlane Trust 124
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1. Chairman’s Report Welcome for the third time to the QEII Centre in London for the 2018 Annual General Meeting of the UKHCDO. The two previous AGMs have been very well attended compared to the preceding meetings held outside London and we thought a larger suite of rooms in this setting would be an ideal venue in which to celebrate the 50th anniversary of the foundation of the National Haemophilia Database. We have invited number of past and retired UKHCDO members to join us and some have accepted; we very much hope they enjoy the educational and social aspects of the meeting.
We have followed the same format as previous years with one or two small changes; we will have an educational day on the Thursday, aiming to cover many current topic issues of scientific and clinical interest. These sessions will be open to all members, our invited past members, guests, Sponsors and some trainees if numbers allow. The Friday sessions will start with an open presentation of the annual statistics and after morning coffee break we will have a business AGM, closed to Members and invited guests only.
The 3rd year of my current term as UKHCDO Chair has again been demanding and challenging but I continue to be supported by my close colleagues at Great Ormond Street Hospital Haemophilia Centre who shoulder the clinical burden and I am extremely grateful and lucky to have them as my team-mates.
When I wrote my report last year the announcement by the Prime Minister that there would be a Public Inquiry to investigate treatment-related infection of haemophiliacs and others in the 70’s-90’s was relatively recent news. We were still waiting to hear which Government department would lead the Inquiry and what the full remit would be. Twelve months on the process is underway; the terms of reference have been developed and published, the preliminary hearings have been heard and the Inquiry is onto the gathering evidence phase. The Inquiry team are making arrangements to visit the National Haemophilia Database where a large volume of archived material is held and they also wish to access relevant parts of the electronic database. The NHD is working with current haemophilia treaters to make sure that the data held is as comprehensive as possible and meanwhile all Trusts with Haemophilia Comprehensive Care and Treatment Centres have been asked by the Inquiry office to search for any relevant documentation at their hospitals that should be disclosed as evidence to the Inquiry Investigators. We are well aware that these current exercises are putting a real burden on our stretched Services but we know that as an Organisation we all recognise the devastating effect that these infections have had on patients and their families and we are all totally committed to helping the Inquiry reach a fully-informed conclusion.
At the same time as at looking back to the misery caused by the transfusion transmitted infections in our patients we have had an enormously exciting year in our treatment journey with a new product available to treat our most difficult patients – those with resistant inhibitors. Emicizumab or Hemlibra has been licensed and received NHS approval to be used and many patients and clinicians have already seen immense benefit with very significant reductions in bleed rate and considerable improvements in quality of life. The pathway to successful adoption of NHSE Policy is a convoluted one but we received unerring support from the Lead Commissioner for Haemophilia - Will Horsley – for both the Emicizumab and the other adopted Policy – the use of recombinant porcine factor VIII in the treatment of bleeding in acquired haemophilia. In the coming months we are going to be working on securing the use of Emicizumab for non-inhibitor patients with an additional Policy and we are hopeful that it is not
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too long before we will be doing the same for other novel treatments including additional new molecules and gene therapy for both haemophilia A and B.
Meanwhile our standard haemophilia A products went through a re-tender process in late 2017 which commenced in February 2018. It was a collaborative project between the UKHCDO and the NHS England Clinical Reference Group (CRG) for Haemophilia and, as with previous tenders, we benefitted from considerable expertise and support from Alison Greenwood and Wendy Roach from the NHSE Commercial Medicines Unit. The tender was highly successful in terms of the projected savings to be realised for the NHS; a number of patients had to switch products and we recognise the inconvenience to patients and the time invested by Centre staff in the administration required to switch patients to realise the savings. In 2018 we also tendered for all the other products that are not recombinant factor VIII and IX; modest savings were achieved here.
Over the last year we have seen progress in a number of UKHCDO initiatives and you will hear about a number of them during the AGM. The Data Analysis Group (DAG) is a sub-group of the Data Management Working Party and it meets by teleconference monthly. The main role of this Group is the assessment and prioritisation of requests for data from a number of sources, many of which generate income which supports the running of the NHD. We have completed reports requested by a number of commercial companies and abstracts and publications have resulted from several of these.
The Clinical Studies Group has been in existence for 2-3 years and has partnered with the James Lind Alliance to establish a Priority Setting Partnership on Bleeding Disorders with the aim of identifying the most important research areas going forwards. The James Lind Alliance runs the Partnership with well-established and validated methodology and brought together patients, carers and health and social care professionals to identify the important unknowns in diagnosis and treatment in the field of bleeding disorders. It has now completed its work and the three highest ranked research priorities in inherited bleeding disorders were: 1. How can we balance the risk and benefit of antithrombotic (blood thinning) treatment for cardiovascular disease (including heart attacks and strokes) in patients with bleeding disorders?; 2. How should heavy periods be managed in women with bleeding disorders?; 3. What are the most effective treatments for acute and chronic pain in people with haemophilia? The full list of the top 10 priorities can be found at http://www.jla.nihr.ac.uk/top-10-priorities/.
Last year during the AGM we introduced the format for the 2018/9 Peer Review process and I am delighted to say that our partnership with the West Midlands Quality Review Service has developed to the ‘almost-there’ stage and the 1st review using these high-quality robust standards will happen in the same month as the AGM. All reviews should be completed by AGM 2019 when we should aim to have a detailed discussion on how the results of the Peer Review can help to shape our Services going forward. I would like to thank John Hanley for his sterling efforts in Chairing the Peer Review Working Party and to the other members on the Group. We also had considerable support from nursing, physio and other colleagues and patient representatives and I would like to thank them for their help with this initiative and other UKHCDO work streams.
Finally, I would like to express my gratitude for the continuing support of the rest of the Executive Committee; Professor Peter Collins as Vice Chair; Dr Kate Talks as Secretary and Dr Pratima Chowdary as Treasurer. Both Pratima and I are up for re-election for a 2nd 3 year term; the outcome of this is not finalised at the time I am writing this report. On behalf of the Executive and all members I would also like to thank Professor Charlie Hay for his sustained
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efforts in running and managing the National Haemophilia Database and all the other members of NHD staff including the statisticians for their hard work in supporting the UKHCDO. Special thanks go to Lynne Dewhurst for her ongoing hard work which has underpinned the continued achievements of the NHD. Lastly – and not at all least - is considerable personal gratitude to Sarah Rooney without whose support the role as UKHCDO Chair would not be remotely manageable.
Dr Ri Liesner, UKHCDO Chair
October 2018
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UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
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Bleeding Disorder Statistics for April 2017 to March 2018
A report from the UK National Haemophilia Database
October 2018
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2. Bleeding Disorder Statistics for 2017 / 2018 Contents
Appendix 1: Glossary ........................................................................................................................ 10
2.0. Comments on the Bleeding Disorder Statistics for 2017 / 2018 .............. 12
2.1 Haemophilia A ........................................................................................ 15
Table 1 Patients with congenital haemophilia A (including carriers) registered and
treated, 2017/018 ................................................................................................ 16
Figure 1 Carriers of haemophilia A currently registered and newly registered, by
baseline factor VIII level, 2017/18 ........................................................................ 17
Table 2 New registrations of haemophilia A (including carriers), by age at mid‐
year, gender and severity, 2017/18 ..................................................................... 18
Table 3 New registrations of patients with severe haemophilia A aged over 2 years
old, and subsequent treatment by year ............................................................... 19
Figure 2a Trend in the number of patients with severe haemophilia A aged 60 years
and above, 1977 – 2017/18 (including HIV +ve pts)............................................. 20
Figure 2b Trend in the number of patients with moderate haemophilia A aged 60
years and above, 1977 – 2017/18 (including HIV +ve pts) ................................... 21
Figure 2c Trend in the number of patients with mild haemophilia A aged 60 years
and above, 1977 – 2017/18 (including HIV +ve pts)............................................. 21
Figure 3 Factor VIII units issued by UK haemophilia centres to treat haemophilia A,
1993 – 2017/18 .................................................................................................... 22
Figure 4 Factor VIII units issued by UK haemophilia centres to treat severe
haemophilia A, 2012/13 ‐ 2017/18 ...................................................................... 23
Figure 5 Factor VIII units per kilogram issued to treat severe haemophilia A,
2012/13 ‐ 2017/18 ................................................................................................ 24
Table 4a Treatment intensity of patients with severe haemophilia A treated with
standard FVIII, with no inhibitor – 2012/13 ‐ 2017/18 ......................................... 25
Table 4b Treatment intensity of patients with severe haemophilia A treated with
enhanced half‐life FVIII, with no inhibitor – 2015/16 ‐ 2017/18 .......................... 26
Table 5a Treatment intensity of patients with moderate haemophilia A treated
with standard FVIII, with no inhibitor – 2012/13 ‐ 2017/18 ................................ 27
Table 5b Treatment intensity of patients with moderate haemophilia A treated
with enhanced half‐life FVIII, with no inhibitor – 2016/17 ‐ 2017/18 .................. 28
Figure 6 Median usage of factor VIII: UK patients with severe haemophilia A
without inhibitors broken down by age, 2012/13 – 2017/18 .............................. 29
Figure 7 Patients with severe / moderate / mild haemophilia A treated with FVIII
by UK haemophilia centres – 2009/10 – 2017/18 ................................................ 30
Table 6 Factor VIII usage by region for patients with severe haemophilia A (incl.
treatment for inhibitors and EHL‐VIII), 2017/18 .................................................. 31
Figure 8a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged
under 18 years with no current inhibitor, by centre, ranked by median
usage ..................................................................................................................... 32
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Figure 8b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged
under 18 years with no current inhibitor, by centre, ranked by median
usage per patient .................................................................................................. 34
Figure 9a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged
18 years or more with no current inhibitor, by centre, ranked by median
usage ..................................................................................................................... 35
Figure 9b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged 18
years or more with no current inhibitor, by centre, ranked by median
usage per patient .................................................................................................. 37
Figure 10 Median factor VIII units issued per kilogram body weight per year in
patients with severe haemophilia A without inhibitors by age ........................... 38
Figure 11 Median factor VIII units issued (IU/kg) in patients with severe haemophilia
A without inhibitors aged 16 and over, by bodyweight ....................................... 39
Figure 12 Patients with severe haemophilia A with no current inhibitor in the
reporting year: median usage by inhibitor history ............................................... 40
Table 7 Products issued to treat haemophilia A (including inhibitors), 2017/18 ............. 41
Table 8 Factor VIII units issued by UK haemophilia centres, by diagnosis. 2017/18 ........ 43
Figure 13 Market Share of factor VIII concentrates issued by UK haemophilia
centres, 2017/18 .................................................................................................. 44
2.2 Haemophilia B ........................................................................................ 45
Table 9 Patients with congenital haemophilia B (including carriers) registered and
treated, 2017/18 .................................................................................................. 46
Figure 14 Carriers of haemophilia B currently registered and newly registered, by
baseline factor IX level, 2017/18 .......................................................................... 47
Table 10 New registrations of haemophilia B (including carriers), by age at mid‐
year, gender and severity, 2017/18 ..................................................................... 48
Figure 15a Trend in numbers of severe haemophilia B patients aged 60 years and
above, 1977 – 2017/18 (including HIV +ve pts).................................................... 49
Figure 15b Trend in numbers of moderate haemophilia B patients aged 60 years and
above, 1977 – 2017/18 (including HIV +ve pts).................................................... 50
Figure 15c Trend in numbers of mild haemophilia B patients aged 60 years and
above, 1977 – 2017/18 (including HIV +ve pts).................................................... 50
Figure 16 Factor IX units issued by UK haemophilia centres to treat haemophilia B,
1993 – 2017/18 .................................................................................................... 51
Table 11 Factor IX usage by region for patients with severe haemophilia B (incl.
treatment for inhibitors and EHL‐IX), 2017/18 .................................................... 52
Table 12 Products issued to treat haemophilia B (including inhibitors), 2017/18 ............. 54
Table 13 Factor IX units issued by UK haemophilia centres, by diagnosis, 2017/18 .......... 55
Figure 17 Market Share of factor IX concentrates issued by UK haemophilia centres,
2017/18 ................................................................................................................ 56
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2.3 Von Willebrand Disease ......................................................................... 57
Table 14 Patients with von Willebrand disease registered and treated April 2017 ‐
March 2018 ........................................................................................................... 58
Table 15 New Registrations of von Willebrand disease between April 2017 & March
2018, by age at mid‐year, severity, and gender ................................................... 60
Figure 18 Factor VIII units issued by UK haemophilia centres to treat Von Willebrand
disease 1993 – 2017/18 ........................................................................................ 61
Table 16 Products issued to treat von Willebrand disease (including inhibitors),
2017/18 ................................................................................................................ 62
2.4 Inhibitors: Congenital and Acquired ........................................................ 63
Table 17 Inhibitors by disease severity – haemophilia A, haemophilia B & von
Willebrand disease ............................................................................................... 64
Table 18 Products issued to patients with congenital bleeding disorders reported
to have a positive inhibitor during 2017/18 ......................................................... 66
Table 19 Products issued to patients with Acquired Inhibitors 2017/18 ............................ 67
Table 20 FEIBA® usage: breakdown by diagnosis ................................................................ 68
Table 21 NovoSeven® usage: breakdown by diagnosis ....................................................... 68
2.5 Rarer Bleeding Disorders ....................................................................... 69
Table 22 Patients with rarer types of bleeding disorders registered and treated
April 2017 & March 2018 ..................................................................................... 70
Table 23 Patients with selected rarer bleeding disorders registered and treated
April 2017 – March 2018, by disease severity ...................................................... 71
Table 24 New registrations of rarer bleeding disorders between April 2017 &
March 2018 showing their coagulation defect and gender ................................. 72
Table 25 Concentrates used to treat rarer bleeding disorders between April 2017
& March 2018 ....................................................................................................... 73
2.6 Adverse Events ...................................................................................... 74
Table 26 Adverse Events reported between April 2017 & March 2018 ............................. 75
2.7 Morbidity and Mortality ........................................................................... 76
Table 27 Causes of death in patients with haemophilia A and B between April 2017
& March 2018 ....................................................................................................... 77
Table 28 Causes of death in other coagulation defects between April 2017 & March
2018 ...................................................................................................................... 78
Figure 19 Cumulative incidence chart of deaths from hepatocellular carcinoma or
liver failure in UK patients with bleeding disorders 1969 ‐ 2017 ......................... 79
Table 29 Summary of patients ‘at risk’ of vCJD for public health purposes who
received UK sourced plasma products as reported by centres ............................ 81
Figure 20 Total number of patients with haemophilia A, haemophilia B or von
Willebrand disease treated by UK haemophilia centres ...................................... 82
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Figure 21 Total number of patients with severe haemophilia A and haemophilia B
treated by UK haemophilia centres ...................................................................... 82
Appendix 2: Participating Centres .................................................................................................... 83
3. Haemtrack Annual Report 2017 ............................................................. 84
Introduction 84
Section 1: Patients’ Haemtrack Usage Analysis 85
Figure 1 Number of patients using Haemtrack and recruitment rate, 2008-2017 85
Figure 2 Comparison of recruitment to Haemtrack by centre for patients with severe haemophilia A: Comprehensive Care Centres (CCCs) in 2017 87
Figure 3 Comparison of recruitment to Haemtrack by centre for patients with severe haemophilia A: Haemophilia Centres (HCs) in 2017 87
Figure 4 Overall compliance in patients with severe haemophilia A, by Comprehensive Care Centre 88
Figure 5 Overall compliance in patients with severe haemophilia A, by Haemophilia Centre 89
Section 2: Patients’ Reporting Analysis 90
Figure 6 Change in the use of different Haemtrack Reporting Media: 2011- 2017 90
Figure 7 Haemtrack Reporting Delay by Reporting Medium 2017 91
Figure 8 Reporting compliance by reporting medium, ranked by median compliance 2017 (CCC’s) in patients with severe haemophilia A 92
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Appendix 1: Glossary
BCSH British Committee for Standards in Haematology
BMI Body mass index
BMS Biomedical Scientist
BPG Best practice guideline
BSA Business Services Authority
BSH British Society for Haematology
CCC Comprehensive Care Centre
CMWP Co-morbidities Working Party
CQUIN Commissioning for Quality and Innovation
DAG Data Analysis Group
DH Department of Health
DMWP Data Management Working Party
EAHAD European Association for Haemophilia and Allied Disorders
ECH European Haemophilia Consortium
EHL Enhanced Half-life
EQA External quality assessment
EU European Union
FVIII Factor VIII
FIX Factor IX
GLN Genetic Laboratory Network
GWP Genetics Working Party
HC Haemophilia Centre
HCC Hepatocellular carcinoma
HCIS Haemophilia Clinical Information System
HCPA Haemophilia Chartered Physiotherapists’ Association
HCV Hepatitis C virus
HEAD-US Hemophilic Early Arthropathy Detection with UltraSound
HIV Human immunodeficiency virus
HJHS Haemophilia Joint Health Score
HNA Haemophilia Nursing Association
ICF International Classification of Function
ICH Intracranial haemorrhage
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IQR Interquartile range
ISO International Organization for Standardization
ITI Immune tolerance induction
IU/dl International units per decilitre
IU/kg International units per kilogram
IWP Inhibitor Working Party
kg Kilogram
MDSAS Medical Data Solutions and Services
MFT The Macfarlane Trust
MSK Musculoskeletal
NEQAS National External Quality Assessment Service
NGS Next generation sequencing
NHD National Haemophilia Database
NHS National Health Service
NHSE NHS England
NIBSC National Institute for Biological Standards and Control
NIHR National Institute for Health Research
PSWD Pulsed shortwave diathermy
PUP Previously untreated patient
PWP Paediatric Working Party
RCOG Royal College of Obstetricians and Gynaecologists
SHL Standard Half-life
TTP Thrombotic thrombocytopenic purpura
TUPE Transfer of Undertakings (Protection of Employment) regulations
UK United Kingdom
UKAS United Kingdom Accreditation Service
UKGTN United Kingdom Genetic Testing Network
UKHCDO United Kingdom Haemophilia Centre Doctors’ Organisation
UKHCDO GLN United Kingdom Genetic Laboratory Network
VWD Von Willebrand disease
VWF Von Willebrand factor
WAPPS-Hemo Web-Accessible Population Pharmacokinetic Service—Hemophilia
WFH World Federation of Hemophilia
WMQRS West Midlands Quality Review Service
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2.0. Comments on the Bleeding Disorder Statistics for 2017 / 2018
The following report details the registration, treatment and mortality statistics for the UK for the year 2017/18. Most of the commentary appears next to the table or figure to which it relates.
Increasingly, this report, focussing as it does on registrations, mortality and adverse events, does not fully reflect the range of activities undertaken by the database in its 50th year. Supplementary reports have been provided for Scotland and Wales. Many supplementary reports have been provided to NHS England and to the Suppliers, particularly those detailing changes in factor VIII/IX usage and annual bleed-rate (ABR) in patients switched to EHL-VIII and EHL-IX. These reports are being made available to be viewed by UKHCDO Members on a secure UKHCDO SharePoint site (not for wider dissemination). Data is also being collected on joint scoring and we would expect to report on this in the future.
Since April 2017 all new proposals and data requests have been reviewed or vetted by the Data Analysis Group (DAG), a subgroup of the Data Management Working Party. This group, which meets monthly by teleconference, is co-chaired by CRM Hay and PW Collins and includes two patient representatives, two statisticians and several working party chairs.
The database also supports a number of other projects, including a reassessment of mortality and life expectancy in patients with haemophilia and an assessment of the current hepatitis C status of patients currently registered.
In addition, UKHCDO and the National Haemophilia Database are cooperating fully with the Infected Blood Inquiry, giving the Inquiry open access to the electronic and paper archive going back 50 years.
Adverse events are listed in this report but are not presented in any detail. Whilst this is not entirely satisfactory, when we reported adverse events in more detail last year concerns were raised in relation to the potential identifiability of individuals and so we felt obliged to revert to the rather uninformative previous format. Adverse events thought to be product-related are reported to the supplier so that they may fulfil their regulatory obligation to investigate adverse events further.
Reports of causes of death continue to be a problem. NHS Digital ceased sending us death certification data about two years ago. We know which of our registered patients have died from the NHS Spine but rely on haemophilia centres to provide the cause of death, which they are unable to do in about a third of cases. We should be grateful if centres could report a higher proportion of causes of death to the database. Centres may not know the cause of death if the patient dies at home or in a different hospital from the reporting haemophilia centre.
It is our aim to renew our contract with NHS Digital to obtain death certification data, but this will depend on the Database being recognised as a Research Database (ethics application submitted) and changing from our current system of implied consent with an opt-out to a system of explicit written consent which will be introduced later this year. We anticipate that consent will have to be obtained face-to face on an opportunist basis with most consents being obtained from patients with severe haemophilia in the first 12 months. This will be a large task, which will require engagement and commitment from centres to ensure a high-level of consent.
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Pharmacovigilance is an increasingly important aspect of the work of the database. The database has conducted and published several post-marketing studies, some mandated by the European Medicines Agency (EMA) and including two PUP studies. Over recent years we have forged an increasingly close working relationship with EMA and representatives of UKHCDO have met with EMA and participated in EMA Workshops on a regular basis. EMA have recently proposed to abandon pre-licensure PUP studies and to rely far more heavily on the real-world data produced by databases for the safety and efficacy data that they require. This is an initiative across the whole of the rare diseases therapeutic area, acknowledging the difficulty that fully powered drug trials are impractical in rare diseases. EMA anticipate that databases will have to collaborate to establish common datasets and potentially to aggregate anonymised data. Funding for this would presumably be obtained from Industry. This proposal is not without its problems not least of which is that databases can only report on the products prescribed by their reporting centres.
It is anticipated that we will shortly embark on the largest such study to date, documenting safety and relative efficacy of Emicizumab (Hemlibra®, Roche) as it is introduced for the treatment of patients with haemophilia A and inhibitors and subsequently for non-inhibitor patients. This is an enormous paradigm shift in the treatment of haemophilia A and it is important that we document outcome and safety, firstly of conventional treatment for within-patient comparison with Hemlibra, once patients have switched.
We would like to thank all Centre Directors and haemophilia centre staff for their hard work in sending us all this data over the past year and for their forbearance in the face of increasing demands. It is very much appreciated.
Professor Charles RM Hay,
Lynne Dewhurst, Ben Palmer & Dr Hua Xiang
On behalf of the UK National Haemophilia Database Manchester, October 2018
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Important Note: Throughout this report, haemophilia A includes carriers of haemophilia A and females with FVIII deficiency.
Haemophilia B includes carriers of haemophilia B, females with FIX deficiency, patients with FIX Leyden and FIX Leyden carriers.
Time Periods: Unless otherwise stated, the tables and figures presented in this report relate to the period April 2017 – March 2018 inclusive.
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2.1 Haemophilia A
Tab
le 1
P
atie
nts
with
con
geni
tal h
aem
ophi
lia A
(in
clud
ing
carr
iers
) re
gist
ered
and
trea
ted,
201
7/01
8
MF
Total
MF
Total
MF
Total
MF
Total
MF
Total
MF
Total
<18 years
702 ‐
702 194 5 199 591 105 696 28 158 186 ‐ 8
8
1,515 276 1,791
≥18 years
1,310 2 1,312 617 2 619 2,515 582 3,097 161 1,116
1,277 3
60
63
4,606 1,762
6,368
Total
2,012 2
2,014 811 7
818 3,106 687
3,793 189 1,274
1,463 3 68
7
1 6,121 2,038
8,159
<18 years
46 ‐
46
15 1
16
52 20
72
4
36
40
‐ 3
3
117 60 177
≥18 years
18 1
19
10 ‐
10
55 22
77
4
86
90
1
8
9
88 117 205
Total
6
4 1 6
5 2
5 1 2
6 107 42
149 8 122
130 1 11
1
2 205 177
382
<18 years
683 ‐
683 147 4 151 170 10 180 4
2
6
1
‐
1
1,005 16 1,021
≥18 years
1,261 ‐
1,261 403 2 405 636 44 680 15 27
42
‐ ‐
‐
2,315 73 2,388
Total
1,944 ‐
1,944 550 6
556 806 5
4 860 1
9 2
9 4
8 1 ‐
1 3,320 89
3,409
<18 years
665 ‐
665 144 4 148 148 5 153 3
2
5
1
‐
1
961 11 972
≥18 years
1,211 ‐
1,211 380 2 382 535 25 560 10 17
27
‐ ‐
‐
2,136 44 2,180
Total
1,876 ‐
1,876 524 6
530 683 3
0 713 1
3 1
9 3
2 1 ‐
1 3,097 55
3,152
Num
ber o
f Patients (Factor VIII le
vel (IU/dl))
< 1
1 ‐ 5
>5 & <40
≥ 40
Unk
nown
Total
Treated with
concentrate in
year**
Hae
mop
hilia
A
Age
Ra
nge
Total In Register
New Registrations *
Treated in
year**
*
New
regi
stra
tions
are
a s
ubse
t of t
he ‘I
n R
egis
ter’
num
bers
**
Tre
ated
incl
udes
pat
ient
s ‘In
Reg
iste
r’ an
d ‘N
ew R
egis
trat
ions
’
Tabl
e 1
show
s th
e to
tal n
umbe
r of
pat
ient
s w
ith h
aem
ophi
lia A
(in
clud
ing
carr
iers
and
def
icie
nt fe
mal
es)
regi
ster
ed in
the
UK
dur
ing
2017
/18
brok
en d
own
by a
ge a
nd d
isea
se s
ever
ity.
Page | 16
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Figure 1 Carriers of haemophilia A currently registered and newly registered, by baseline factor VIII level, 2017/18
0
100
200
300
400
500
600
700
800
<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/K
2 13
68
205
364395
776
381 1 3 12 27
5276
5
Patie
nts (n)
Factor FVIII level (IU/dl)
Haemophilia A CarrierIn Register
(Excl. new registrations)
Haemophilia A CarrierNew Registrations
N.B: Includes carriers of haemophilia A and females with FVIII deficiency
<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/KGrand Total
Haemophilia A Carrier
In Register
(Excl. new registrations)
2 13 68 205 364 395 776 38 1,861
Haemophilia A Carrier
New Registrations1 1 3 12 27 52 76 5 177
Total 3 14 71 217 391 447 852 43 2,038
Diagnosis Number of Patients (Factor VIII level (IU/dl))
Figure 1 shows the number of carriers of haemophilia A currently registered with the NHD by baseline factor VIII level. This includes females registered by their centre as having factor VIII deficiency or haemophilia A. New registrations of unaffected carriers continue but are not yet complete. Very low levels amongst carriers are perhaps not quite as rare as might have been expected. Although this is usually accounted for by extreme lyonisation, two patients with levels <2 IU/dl are compound heterozygotes for mutations which cause severe haemophilia.
Tab
le 2
N
ew r
egis
trat
ions
of h
aem
ophi
lia A
(in
clud
ing
carr
iers
), b
y ag
e at
mid
-yea
r, g
ende
r an
d se
verit
y, 2
017/
18
Hae
mop
hilia
A MF
Total
MF
Total
MF
Total
MF
Total
MF
Total
MF
Total
0 ‐ < 2
38
‐
38
12
‐
12
23
5
28
2
4
6
‐
‐
‐
75
9
84
2 : 4
5
‐
5
1
‐
1
8
1
9
1
3
4
‐
‐
‐
15
4
19
5 : 9
‐
‐
‐
2
‐
2
9
9
18
1
10
11
‐
1
1
12
20
32
10 : 19
8
‐
8
2
1
3
14
8
22
‐
22
22
‐
3
3
24
34
58
20 : 29
8
‐
8
3
‐
3
6
8
14
2
23
25
1
1
2
20
32
52
30 : 39
4
1
5
3
‐
3
13
4
17
‐
29
29
‐
3
3
20
37
57
40 : 49
‐
‐
‐
1
‐
1
8
4
12
‐
10
10
‐
1
1
9
15
24
50 : 59
‐
‐
‐
1
‐
1
5
3
8
‐
9
9
‐
2
2
6
14
20
60 : 69
1
‐
1
‐
‐
‐
11
‐
11
‐
8
8
‐
‐
‐
12
8
20
70 +
‐
‐
‐
‐
‐
‐
10
‐
10
2
4
6
‐
‐
‐
12
4
16
Total
641
6525
126
107
42149
8122
130
111
12205
177
382
Num
ber o
f Patients (Factor VIII le
vel (IU/dl))
Age
(yea
rs)
> 5 & < 40
≥ 40
Unk
nown
1 ‐ 5
< 1
Total
Tabl
e 2:
Thi
s sh
ows
the
num
ber
of n
ew r
egis
trat
ions
of h
aem
ophi
lia A
bro
ken
dow
n by
rep
orte
d se
verit
y an
d ag
e at
mid
-yea
r (3
0/09
/201
7).
The
und
erly
ing
birt
h ra
te o
f pat
ient
s w
ith s
ever
e ha
emop
hilia
A b
orn
in th
e U
K r
uns
at 4
0-45
pat
ient
s pe
r ye
ar.
Ove
r 40
% o
f new
reg
istr
atio
ns
of s
ever
e ha
emop
hilia
A w
ere
regi
ster
ed a
ged
two
year
s or
abo
ve.
All
of t
hese
pat
ient
s ar
e re
cent
mig
rant
s to
thi
s co
untr
y.
Just
und
er h
alf
of th
ese
patie
nts
com
e fr
om th
e w
ider
EU
, som
e of
who
m s
tay
for
only
a fe
w m
onth
s to
a y
ear
or s
o. T
he r
emai
nder
orig
inat
e fr
om th
e re
st o
f th
e w
orld
. T
his
appe
ars
to b
e a
stab
le tr
end
over
rec
ent y
ears
(se
e ta
ble
3).
Page | 18
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Tab
le 3
N
ew r
egis
trat
ions
of p
atie
nts
with
sev
ere
haem
ophi
lia A
age
d ov
er 2
yea
rs o
ld, a
nd s
ubse
quen
t tre
atm
ent b
y ye
ar
Haem
ophilia
A2008/09
2009/10
2010/11
2011/12
2012/13
2013/14
2014/15
2015/16
2016/17
2017/18
New
registratio
ns / ye
ar18
1413
1812
2322
2723
22170
2008/09
181
19
2009/10
1710
27
2010/11
1611
1239
2011/12
1511
1117
54
2012/13
1311
917
1161
2013/14
1410
1015
1122
82
2014/15
1310
1015
1122
21102
2015/16
1311
813
1121
2126
124
2016/17
1210
713
1121
1922
232
140
2017/18
1210
710
1020
1918
2319
148
No treatment records
01
10
10
00
03
6
Total
2008/2018
Reg
istration ye
ar
Trea
ted in each ye
ar
Tabl
e 3:
T
his
show
s th
e nu
mbe
r of
pat
ient
s ov
er t
wo
year
s of
age
and
new
ly r
egis
tere
d (a
nd t
here
fore
tho
ught
to
be m
igra
nts)
eac
h ye
ar
from
200
8/09
. It
also
sho
ws
the
num
ber
trea
ted
in e
ach
year
sub
sequ
ent t
o th
eir
regi
stra
tion.
Thi
s sh
ows
that
pot
entia
lly a
t lea
st 1
70 p
atie
nts
with
sev
ere
haem
ophi
lia A
hav
e m
igra
ted
to t
he U
K s
ince
200
8/09
. T
his
is li
kely
to
be a
n un
dere
stim
ate,
sin
ce c
hild
ren
two
year
s ol
d an
d un
der
are
not i
nclu
ded
in th
is ta
ble.
Alth
ough
six
pat
ient
s in
the
tabl
e re
quire
d no
trea
tmen
t, 14
8 of
them
wer
e tr
eate
d in
201
7/18
, sug
gest
ing
that
mos
t rem
ain
and
requ
ire r
egul
ar tr
eatm
ent.
Page | 19
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 20
Figure 2a Trend in the number of patients with severe haemophilia A aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)
N.B. Carriers included in figures 2a – 2c
Figure 2a shows a more than doubling in the number of patients with severe haemophilia aged 60-74, and in those aged 75 and above, over the past forty years. The number of elderly patients with severe haemophilia A actually declined during the 1990’s because of deaths from HIV and HCV, recovering subsequently, as treatment improved.
Figure 2b (overleaf) The effect of HIV is not seen as markedly in moderate severity haemophilia A because proportionately fewer of these patients were infected. The number of patients aged greater than 60 years increased three-fold over the past 40 years. Some of this increase is probably attributable to better diagnosis rather than increasing lifespan.
Figure 2c (overleaf) shows the age trend for mild haemophilia A. This is difficult to interpret since the increased number may reflect increased diagnosis rather than just increased life expectancy.
02
04
06
08
01
00
60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+
1977 1987 1997 2007 2017/18
Pa
tien
ts (
n)
Age group (years) by reporting yearGraphs by year
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 21
Figure 2b Trend in the number of patients with moderate haemophilia A aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)
Figure 2c Trend in the number of patients with mild haemophilia A aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)
02
04
06
08
01
00
60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+
1977 1987 1997 2007 2017/18
Pa
tien
ts (
n)
Age group (years) by reporting yearGraphs by year
01
002
003
004
005
006
00
60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+
1977 1987 1997 2007 2017/18
Pa
tien
ts (
n)
Age group (years) by reporting yearGraphs by year
0500
1,00
0
1,50
0
2,00
0
2,50
0
3,00
0
3,50
0
0
100
200
300
400
500
600
Pa�ents (n)
Units(millions)
Tim
e Pe
riod
Plas
ma
Reco
mbi
nant
Inve
s�ga�o
nal
EHL
Pa�e
nts t
reat
ed
Figu
re 3
Fa
ctor
VIII
uni
ts is
sued
by
UK
hae
mop
hilia
cen
tres
to tr
eat h
aem
ophi
lia A
, 199
3 – 2
017/
18
N.B
: Dat
a fo
r St T
hom
as’ w
ere
not s
ubm
itted
199
6-20
06.
Figu
re 3
sho
ws
UK
fact
or V
III u
nits
issu
ed to
trea
t hae
mop
hilia
A b
etw
een
1993
to 2
017/
18.
The
num
ber o
f pat
ient
s re
porte
d to
hav
e be
en
treat
ed is
sho
wn
by th
e bl
ue li
ne u
sing
a s
econ
dary
axi
s. T
his
show
s pa
tient
num
bers
hav
e in
crea
sed
by o
ver 4
0% d
urin
g th
is ti
me
whe
reas
fa
ctor
VIII
usa
ge h
ad m
ore
than
qua
drup
led.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
| egaP 22
Fig
ure
4 F
acto
r V
III u
nits
issu
ed b
y U
K h
aem
ophi
lia c
entr
es to
trea
t sev
ere
haem
ophi
lia A
, 201
2/13
- 2
017/
18
IU (000
)
% differen
cesince
201
2/13
IU(000)
% differen
cesince
201
2/13
IU(000)
% differen
cesince
201
2/13
IU(000)
% differen
cesince
201
5/16
IU(000)
% differen
cesince
201
2/13
n
% differen
cesince
201
2/13
2012/13
34,072
100.00
344,322
100.00
7,871
100.00
0386,266
100.00
1,638
100.00
2013/14
30,780
90.34
364,514
105.86
18,462
234.55
0413,756
107.12
1,701
103.85
2014/15
32,932
96.65
395,614
114.90
17,476
222.02
0446,022
115.47
1,746
106.59
2015/16
32,081
94.15
419,302
121.78
14,317
181.89
285
100.00
465,985
120.64
1,793
109.46
2016/17
28,176
82.70
430,835
125.13
9,740
123.75
12,986
4552.61
481,738
124.72
1,833
111.90
2017/18
21,791
63.96
402,194
116.81
5,715
72.60
60,380
21167.33
490,080
126.88
1,876
114.53
Patie
nts T
reated
Year
Plasma
Recombina
nt
(excluding inve
stigational)
Inve
stigationa
l rFV
IIITo
tal
Enha
nced
Half‐L
ife FV
III
Figu
re 4
sho
ws
a ba
r di
agra
m o
f fa
ctor
VIII
usa
ge f
or
seve
re
haem
ophi
lia
A
in
the
UK
fr
om
2012
/13
to
2017
/18
(incl
udin
g in
hibi
tors
).
The
num
ber
of p
atie
nts
repo
rted
to h
ave
been
trea
ted
is s
how
n by
the
blue
line
us
ing
a se
cond
ary
axis
. T
his
show
s a
14.5
% in
crea
se
in
patie
nt
num
bers
ov
er
that
pe
riod
but
a 26
.9%
in
crea
se i
n pr
oduc
t us
e.
Thi
s ha
s se
en f
acto
r V
III
cons
umpt
ion
for
seve
re h
aem
ophi
lia A
inc
reas
e fr
om
386
mill
ion
units
in
2012
/13
to 4
90 m
illio
n un
its i
n 20
17/1
8.
Thi
s in
crea
se in
usa
ge is
larg
ely
attr
ibut
able
to
in
crea
sed
num
bers
of
pa
tient
s an
d in
crea
sed
indi
vidu
al
body
wei
ght
but
also
in
tens
ifica
tion
of
prop
hyla
xis.
N
ote
that
thi
s gr
aph
and
tabl
e in
clud
e pa
tient
s w
ith i
nhib
itors
and
are
the
refo
re n
ot d
irect
ly
com
para
ble
with
tabl
e 4a
.
Dat
a ta
ble
for f
igur
e 4
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 23
1,500
1,550
1,600
1,650
1,700
1,750
1,800
1,850
1,900
0
100
200
300
400
500
600
2012
/13
2013
/14
2014
/15
2015
/16
2016
/17
2017
/18
Patients (n)
Units(millions)
Time Pe
riod
Plasm
aReco
mbinant
Inve
stigational
EHL
Patients Treated
Fig
ure
5 F
acto
r V
III u
nits
per
kilo
gram
issu
ed to
trea
t sev
ere
haem
ophi
lia A
, 201
2/13
- 2
017/
18
Fig
ure
5 sh
ows
a ba
r di
agra
m o
f fac
tor
VIII
usa
ge in
IU/k
g fo
r pa
tient
s w
ith s
ever
e ha
emop
hilia
A.
Thi
s ta
ble/
diag
ram
is
not
dire
ctly
com
para
ble
with
the
pre
viou
s ta
ble.
T
his
show
s th
at,
sinc
e 20
12/1
3 th
e nu
mbe
r of
pat
ient
s w
ith
repo
rted
w
eigh
t ha
s in
crea
sed
by
10.6
%,
and
now
co
mpr
ises
82
.6%
of
F
VIII
-tre
ated
pa
tient
s w
ith
seve
re
haem
ophi
lia A
. M
edia
n us
age/
Kg
has
rem
aine
d al
mos
t un
chan
ged
durin
g th
is
perio
d,
impl
ying
th
at
trea
tmen
t in
tens
ity
(per
kg
) is
re
lativ
ely
stab
le.
T
he
med
ian
body
wei
ght
of p
atie
nts
with
hae
mop
hilia
A i
ncre
ased
by
1.4%
dur
ing
the
perio
d 20
12/1
3-20
17/1
8.
Incr
ease
d fa
ctor
VIII
usa
ge p
er-p
atie
nt i
s th
eref
ore
only
pa
rtly
attr
ibut
able
to
incr
ease
d bo
dyw
eigh
t. I
ncre
ased
ov
eral
l us
age
is l
arge
ly a
ttrib
utab
le t
o in
crea
sed
patie
nt
num
bers
.
Dat
a ta
ble
for f
igur
e 5
Page | 24
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Med
ian
IU/Kg
% differen
cesince
201
2/13
Med
ian
IU/Kg
% differen
cesince
201
2/13
Med
ian
IU/Kg
% differen
cesince
201
2/13
Med
ian
IU/Kg
% differen
cesince
201
5/16
Med
ian
IU/Kg
% differen
cesince
201
2/13
n% differen
cesince
201
2/13
2012/13
5,939
100.00
3,527
100.00
2,780
100.00
3,638
100.00
1,400
100.00
2013/14
5,809
97.81
3,616
102.52
3,886
139.78
3,799
104.43
1,643
117.36
2014/15
6,301
106.10
3,790
107.46
4,428
159.28
3,966
109.02
1,433
102.36
2015/16
5,632
94.83
3,843
108.96
5,283
190.04
859.00
100.00
3,961
108.88
1,442
103.00
2016/17
5,222
87.93
3,769
106.86
2,348
84.46
1129.00
131.43
3,979
109.37
1,574
112.43
2017/18
3,727
62.75
3,526
99.97
1,545
55.58
2743.00
319.32
3,822
105.06
1,549
110.64
Patie
nts w
ith a kn
own
weigh
tYe
ar
Plasma
Recombina
nt
(excluding inve
stigational)
Inve
stigationa
l rFV
IIITo
tal
Enha
nced
Half‐L
ife FV
III
1,250
1,300
1,350
1,400
1,450
1,500
1,550
1,600
1,650
1,700
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
2012
/13
2013
/14
2014
/15
2015
/16
2016
/17
2017
/18
Patients (n)
Median Units per Kg
Time Pe
riod
Reco
mbinant
Plasm
aInve
stigational
Enhan
ced Half‐Life
Patients w
ith a known w
eight
Tab
le 4
a T
reat
men
t int
ensi
ty o
f pat
ient
s w
ith s
ever
e ha
emop
hilia
A tr
eate
d w
ith s
tand
ard
FV
III, w
ith n
o in
hibi
tor
– 201
2/13
-
2017
/18
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
2012/13
96,937,920
240,820,413
557
970
174,036
248,268
100.0
100.0
2013/14
103,552,817
266,497,744
582
1,028
177,926
259,239
102.2
104.4
2014/15
108,337,422
290,704,773
578
1,070
187,435
271,687
107.7
109.4
2015/16
107,747,690
306,430,481
574
1,109
187,714
276,312
107.9
111.3
2016/17
109,410,917
317,871,728
570
1,149
191,949
276,651
110.3
111.4
2017/18
97,546,514
290,942,676
514
1,128
189,779
257,928
109.0
103.9
Patie
nts
(n)
Trea
tmen
t Inten
sity
(Units/Pt)
Chan
ge in
trea
tmen
t intensity
since
201
2/13
(%)
FVIII Units
Treatmen
t Pe
riod
Tabl
e 4a
: T
his
show
s th
at S
HL
FV
III (
stan
dard
hal
f-lif
e F
VIII
) tr
eatm
ent i
nten
sity
(un
its/p
atie
nt/y
ear)
for
seve
re h
aem
ophi
lia A
has
incr
ease
d by
9%
in c
hild
ren
and
4% in
adu
lts w
ith s
ever
e ha
emop
hilia
A (
but n
o in
hibi
tor)
in th
e la
st s
ix y
ears
.
The
incr
ease
in t
reat
men
t in
tens
ity in
adu
lts w
ith s
ever
e ha
emop
hilia
A p
roba
bly
refle
cts
a co
mbi
natio
n of
incr
ease
d bo
dyw
eigh
t, in
crea
sed
use
of p
roph
ylax
is a
nd in
crea
sed
inte
nsity
of p
roph
ylax
is.
At t
he s
ame
time,
the
num
ber
of a
dult
patie
nts
trea
ted
with
SH
L F
VIII
has
incr
ease
d by
16%
, muc
h of
whi
ch is
pro
babl
y ca
used
by
inw
ard
mig
ratio
n.
The
incr
ease
in t
he n
umbe
r of
SH
L F
VIII
uni
ts is
sued
up
until
201
6/17
was
at
trib
utab
le t
o a
com
bina
tion
of g
reat
er t
reat
men
t in
tens
ity a
nd a
sig
nific
ant
incr
ease
in
the
num
ber
of p
atie
nts
with
sev
ere
haem
ophi
lia A
tr
eate
d. H
owev
er, t
he n
umbe
r of
SH
L F
VIII
uni
ts is
sued
fell
in 2
017/
18 fo
llow
ing
the
intr
oduc
tion
of E
HL
FV
III (
enha
nced
hal
f-lif
e F
VIII
).
Page | 25
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Tab
le 4
b T
reat
men
t int
ensi
ty o
f pat
ient
s w
ith s
ever
e ha
emop
hilia
A tr
eate
d w
ith e
nhan
ced
half-
life
FV
III, w
ith n
o in
hibi
tor
– 20
15/1
6 -
2017
/18
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
2016/17
4,533,066
7,266,250
6467
70,829
108,451
100.0
100.0
2017/18
21,024,200
36,708,348
153
185
137,413
198,424
194.0
183.0
Chan
ge in
trea
tmen
t intensity
since
201
5/16
(%)
Treatmen
t Pe
riod
Enha
nced
half‐life FV
III Units
Patie
nts
(n)
Trea
tmen
t Inten
sity
(Units/Pt)
Tabl
e 4b
sho
ws
the
intr
oduc
tion
of E
HL
FV
III fo
r th
e tr
eatm
ent o
f sev
ere
haem
ophi
lia A
from
Sep
tem
ber
2016
to A
pril
2018
. T
he n
umbe
r of
pa
tient
s tr
eate
d in
crea
sed
by 1
58%
ove
r th
e la
st tw
o ye
ars
as m
ore
patie
nts
wer
e ch
ange
d to
the
prod
uct.
The
dra
mat
ic, a
lmos
t dou
blin
g of
tr
eatm
ent i
nten
sity
ove
r th
e tw
o ye
ars
is d
ue to
the
intr
oduc
tion
of E
HL
FV
III o
nly
halfw
ay th
roug
h th
e fir
st y
ear.
NO
TE
: Tab
les
4a &
4b
and
tabl
es 5
a &
5b
– Pat
ient
s tr
eate
d w
ith b
oth
EH
L an
d no
n-E
HL
FV
III a
nd th
eir
usag
e ar
e co
unt i
n bo
th ta
bles
.
Page | 26
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Tab
le 5
a T
reat
men
t in
tens
ity o
f pat
ient
s w
ith m
oder
ate
haem
ophi
lia A
tre
ated
with
sta
ndar
d F
VIII
, with
no
inhi
bito
r –
2012
/13
- 20
17/1
8
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
2012/13
10,401,048
40,611,931
140
346
74,293
117,376
100.0
100.0
2 (1,4)
2013/14
12,674,000
42,371,979
149
361
85,060
117,374
114.5
100.0
2 (1,4)
2014/15
14,624,450
43,322,246
147
361
99,486
120,006
133.9
102.2
2.4 (1,4)
2015/16
14,164,750
47,552,983
138
376
102,643
126,471
138.2
107.7
3 (1,4)
2016/17
14,446,470
49,180,519
135
364
107,011
135,111
144.0
115.1
2.1 (1,4)
2017/18
12,471,928
43,715,859
139
353
89,726
123,841
120.8
105.5
3 (1,4)
Med
ian
(IQR)
Chan
ge in
trea
tmen
t intensity
since
201
2/13
(%)
Treatmen
t Pe
riod
FVIII Units
Patie
nts T
reated
(n)
Trea
tmen
t Inten
sity
(Units/Pt)
Tabl
e 5a
: Thi
s ta
ble
show
s tr
ends
in tr
eatm
ent i
nten
sity
of m
oder
ate
seve
rity
haem
ophi
lia o
ver
the
last
six
yea
rs.
Onl
y pa
tient
s tr
eate
d du
ring
this
tim
e ar
e in
clud
ed.
How
ever
, a r
ange
of b
asel
ine
fact
or V
III le
vels
and
ble
edin
g ph
enot
ypes
will
be
incl
uded
in th
is d
ata
from
pat
ient
s on
re
gula
r pr
ophy
laxi
s to
tho
se r
equi
ring
only
occ
asio
nal t
reat
men
t. T
his
rend
ers
the
data
mor
e di
fficu
lt to
inte
rpre
t an
d im
poss
ible
to
com
pare
di
rect
ly w
ith t
he r
elat
ivel
y m
ore
hom
ogen
eous
gro
up o
f pa
tient
s w
ith s
ever
e ha
emop
hilia
A.
Alth
ough
SH
L F
VIII
tre
atm
ent
inte
nsity
of
mod
erat
e ha
emop
hilia
app
ears
to
have
incr
ease
d in
bot
h ag
e-gr
oups
prio
r to
the
intr
oduc
tion
of E
HL
FV
III,
in 2
017/
18 it
was
less
tha
n 50
%
of t
hat
foun
d in
pat
ient
s w
ith s
ever
e ha
emop
hilia
. F
urth
erm
ore,
Hae
mtr
ack
data
sug
gest
s th
at p
atie
nts
with
mod
erat
e se
verit
y ha
emop
hilia
m
ay b
e re
lativ
ely
unde
r-tr
eate
d. T
his
is a
n ar
ea o
f hae
mop
hilia
ther
apy
that
req
uire
s cl
oser
inve
stig
atio
n.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 27
Tab
le 5
b T
reat
men
t int
ensi
ty o
f pat
ient
s w
ith m
oder
ate
haem
ophi
lia A
trea
ted
with
enh
ance
d ha
lf-lif
e F
VIII
, with
no
inhi
bito
r –
2016
/17
- 20
17/1
8
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
<18 Ye
ars
≥18 ye
ars
2016/17
485,000
1,288,000
916
53,889
80,500
100.0
100.0
2017/18
1,222,500
7,123,500
1135
111,136
203,529
206.2
252.8
Chan
ge in
trea
tmen
t intensity
since
2015/16 (%)
Treatmen
t Pe
riod
Enha
nced
half‐life FV
III Units
Patie
nts
(n)
Trea
tmen
t Inten
sity
(Units/Pt)
Tabl
e 5b
: T
able
5b
Illus
trat
es t
he i
ntro
duct
ion
of E
HL
FV
III t
o a
rela
tivel
y sm
all
grou
p of
pat
ient
s w
ith m
oder
ate
seve
rity
haem
ophi
lia A
be
twee
n S
epte
mbe
r 20
16 a
nd A
pril
2018
. T
his
appe
ars
to s
how
a m
arke
d in
crea
se i
n tr
eatm
ent
inte
nsity
in
both
age
gro
ups
due
to t
he
intr
oduc
tion
of E
HL
FV
III o
nly
halfw
ay th
roug
h th
e fir
st y
ear.
Page | 28
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 29
Figure 6 Median usage of factor VIII: UK patients with severe haemophilia A without inhibitors broken down by age, 2012/13 – 2017/18
N.B. figure based on total usage, not units/kg
Data table for Figure 6
Figure 6: This shows median, IQR and arithmetic range of factor VIII usage by all UK patients with severe haemophilia A without inhibitors, broken down by age and year. This shows a general upward trend in the number of units issued per year in all age groups, similar to table 4a (see data table). This is consistent with the earlier suggestion that prophylaxis may be used more extensively than previously in older age groups. Since prophylaxis has been the standard of care in children since 1996, this increase in treatment intensity amongst children suggests increased intensity of prophylaxis over the years in these groups.
Age Range(years)
Change in median unitsfrom 2012/13 to 2017/18
(%)0‐9 22.9
10‐19 12.9
20‐49 4.2
50‐59 ‐0.3
60+ 22
Fig
ure
7 P
atie
nts
with
sev
ere
/ mod
erat
e / m
ild h
aem
ophi
lia A
trea
ted
with
FV
III b
y U
K h
aem
ophi
lia c
entr
es –
2009
/10
– 201
7/18
Haem
ophilia
A
In Reg
% ch
ange
In Reg
% ch
ange
In Reg
% ch
ange
In Reg
% ch
ange
nn
(%)
since
2008
/09
nn
(%)
since
2008
/09
nn
(%)
since
2008
/09
nn
(%)
since
2008
/09
2008/09
1653
1516
(91.7)
100.0
801
522(65.2)
100.0
3071
558(18.2)
100.0
558
22(3.9)
100.0
2009/10
1683
1542
(91.6)
101.7
807
501(62.1)
96.0
3120
615(19.7)
110.2
584
27(4.6)
122.7
2010/11
1714
1578
(92.1)
104.1
810
510(63.0)
97.7
3171
638(20.1)
114.3
602
26(4.3)
118.2
2011/12
1746
1623
(93.0)
107.1
807
523(64.8)
100.2
3233
641(19.8)
114.9
615
20(3.3)
90.9
2012/13
1777
1638
(92.2)
108.0
806
497(61.7)
95.2
3360
638(19.0)
114.3
755
21(2.8)
95.5
2013/14
1830
1701
(93.0)
112.2
804
526(65.4)
100.8
3412
643(18.8)
115.2
876
21(2.4)
95.5
2014/15
1877
1746
(93.0)
115.2
804
526(65.4)
100.8
3538
638(18.0)
114.3
1083
21(1.9)
95.5
2015/16
1934
1793
(92.7)
118.3
806
526(65.3)
100.8
3661
660(18.0)
118.3
1209
21(1.7)
95.5
2016/17
1969
1833
(93.1)
120.9
805
513(63.7)
98.3
3709
638(17.2)
114.3
1344
25(1.9)
113.6
2017/18
2015
1876
(93.1)
123.7
818
530(64.8)
101.5
3792
713(18.8)
127.8
1463
32(2.2)
145.5
Num
ber o
f Patients (Factor VIII le
vel (IU/dl))
<11 ‐ 5
>5 & <40
≥ 40
Treatmen
t Ye
ar
Trea
ted
Trea
ted
Trea
ted
Trea
ted
Tabl
e 6
(ove
rleaf
): T
his
show
s fa
ctor
VIII
usa
ge b
y co
untr
y an
d co
mm
issi
onin
g re
gion
, ran
ked
by th
e m
ean
num
ber
of u
nits
issu
ed p
er p
atie
nt
with
sev
ere
haem
ophi
lia A
. T
his
sugg
ests
a w
ider
ran
ge o
f clin
ical
pra
ctic
e fr
om r
egio
n to
reg
ion
as o
bser
ved
last
yea
r.
Usa
ge p
er c
apita
of
popu
latio
n is
als
o re
port
ed.
Usa
ge p
er c
apita
for
Sco
tland
is b
roke
n do
wn
into
Eas
t an
d W
est
of S
cotla
nd.
Nor
ther
n Ir
elan
d an
d E
ngla
nd a
re fa
irly
clos
ely
mat
ched
.
Page | 30
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Tab
le 6
F
acto
r V
III u
sage
by
regi
on fo
r pa
tient
s w
ith s
ever
e ha
emop
hilia
A (
incl
. tre
atm
ent f
or in
hibi
tors
and
EH
L-V
III),
201
7/18
Region
Gen
eral
Popu
latio
n
Patie
nts
trea
ted
(n)
Total FVIII
(IU)
Mea
n Usage
FVIII Units
Per C
apita
East of En
glan
d6,168,432
132
42,484,070
321,849
6.89
Yorkshire and the Humber
5,450,130
131
41,780,500
318,935
7.67
London
8,825,001
317
95,341,906
300,763
10.80
North East
2,644,727
6017,102,000
285,033
6.47
South East
9,080,825
299
77,784,940
260,150
8.57
South W
est
5,559,316
136
34,887,000
256,522
6.28
North W
est
7,258,627
194
43,657,000
225,036
6.01
East M
idlands
4,771,666
161
34,194,128
212,386
7.17
West M
idlands
5,860,706
159
31,386,082
197,397
5.36
Englan
d55,619,430
1,589
418,617,626
263,447
7.53
Northern Ireland
1,870,834
7215,002,250
208,365
8.02
Scotlan
d East
3,051,000
7722,504,000
292,260
7.38
Scotlan
d W
est
2,373,800
6115,223,250
249,561
6.41
Wales
3,125,165
7618,614,580
244,929
5.96
United King
dom
66,040,229
1,875
489,961,706
261,313
7.42
Seve
re Hae
mop
hilia
A
Eng
lish
regi
ons
rank
ed b
y m
ean
usag
e
Sou
rce
accr
edita
tion:
Pop
ulat
ion
Est
imat
es fo
r UK
, Eng
land
and
Wal
es, S
cotla
nd a
nd N
orth
ern
Irel
and:
Mid
-201
7: O
ffice
for N
atio
nal S
tatis
tics
licen
sed
unde
r the
Ope
n G
over
nmen
t Lic
ence
v.3
.0.
© C
row
n co
pyrig
ht 2
018
Mid
-201
7 po
pula
tion
estim
ates
Sco
tland
sup
plie
d by
Nat
iona
l Rec
ords
of S
cotla
nd u
nder
the
Ope
n G
over
nmen
t Lic
ence
v3.
0 ©
Cro
wn
Cop
yrig
ht 2
018
NO
TE
: Pat
ient
s ar
e al
loca
ted
to e
ach
regi
on b
ased
on
thei
r ho
me
post
code
, rat
her t
han
whe
re th
ey w
ere
trea
ted
Page | 31
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 32
Note on Figures 8a&b and Figures 9a&b
Patients treated at more than one centre during the year have all their usage attributed to the centre where they received the most units.
Centres with 4 or fewer patients or between 5-9 patients have been aggregated, and all other centres reported individually.
The boxes show the median and 25th and 75th percentiles, and the whiskers show the arithmetic range of FVIII usage, excluding outliers.
Indicated outside values show where a patient's usage is more than 1.5 times the interquartile range (IQR) from the nearest quartile at centre level rather than by reference to practice in the UK as a whole. Outliers in some centres therefore use less than patients not identified as outliers in other centres.
The vertical green line indicates the 95th percentile of units for the whole group (14,048 units per kilogram)
The vertical red line indicates a break in the axis in order to illustrate extreme outliers.
Figure 8a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged under 18 years with no current inhibitor, by centre, ranked by
median usage
N.B: The 95th percentile of units = 13,846 units per kilogram
Figure 8a: This shows factor VIII usage per kilogram per patient by haemophilia centre, ranked by median usage, in patients with severe haemophilia A aged under 18 years old with no reported current inhibitor and an up-to-date bodyweight reported in the previous 12 months.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 33
This shows a 2-fold range in median treatment intensity between centres This implies a wide range in the intensity of prophylaxis used for children with haemophilia in the UK. Most centres have broadly similar treatment intensity, as one would expect, given that prophylaxis is the standard of care. The difference in practice at the extremes is not easily explained for some centres. However, those centres such as Great Ormond Street, who conduct a far greater number of Immune Tolerance Induction procedures than other paediatric centres, will be expected to have high median usage. Although this chart excludes patients with a reported current inhibitor, they may have a higher proportion of patients with unreported low-level inhibitors. It is now well recognised that some patients who fulfil the internationally recognised criteria for tolerance (half-life greater than eight hours), and who have traditionally been thought to be inhibitor free, continue to have low level inhibitor activity, which is too low to detect in the Bethesda assay but high enough to impair factor VIII pharmacokinetics and increase factor VIII consumption. Figure 12 shows that patients aged under 18 years with a past inhibitor history, but currently thought to be inhibitor-free, nevertheless use on average 23.5% more factor VIII than those with no past inhibitor history (p<0.005).
Summary statistics for this chart are presented in the accompanying data table.
Data table for Figures 8a & b
Haemophilia CentrePatients treated
Patients treated with
weight reported
Total UnitsMedian Units
Median Units/Kg
Belfast Adults' 11 9 2,902,000 268,000 3,824
Belfast Children's 14 3 1,502,000 103,250 3,435
Birmingham 45 38 6,593,701 132,000 3,833
Bristol 23 19 5,079,750 189,000 5,976
Cambridge 21 21 3,294,000 108,000 4,930
Canterbury 15 8 2,951,500 142,750 6,620
Cardiff 13 13 3,153,000 216,500 5,386
Edinburgh 10 10 2,590,500 92,125 5,293
Glasgow 26 26 5,906,500 146,000 6,623
Great Ormond Street 83 78 22,990,341 242,000 6,810
Leeds 23 22 5,344,250 225,000 7,675
Leicester 11 10 1,420,800 113,250 5,121
Liverpool 25 23 4,198,500 112,500 5,646
Manchester 50 45 8,023,000 134,875 5,027
Newcastle upon Tyne 19 19 3,732,250 195,000 3,963
North Hampshire 19 19 3,945,750 202,000 5,449
Nottingham 17 17 2,514,000 121,000 4,394
Oxford 32 32 6,873,750 193,250 4,535
Royal London 19 18 3,567,872 156,000 3,518
Sheffield 19 8 3,489,000 126,250 4,170
St Thomas' 24 14 3,898,000 156,500 4,785
Centres with <=4 patients meeting criteria 17 12 5,187,250 312,500 6,136
Centres with 5‐9 patients meeting criteria 53 47 9,583,250 162,000 5,141
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 34
Figure 8b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged under 18 years with no current inhibitor, by centre, ranked by median
usage per patient
N.B: The 95th percentile of units = 452,500 IU
Figure 8b: This shows usage per patient aged under 18 years by centre, for patients with severe haemophilia A with no reported current inhibitor as in the previous figure but not corrected for bodyweight. It shows a three-fold range in median units used per patient between centres, and interpretation is similar to the previous figure, though the sample size is slightly larger since all patients are included and not just those for whom current bodyweight is known.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 35
Figure 9a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged 18 years or more with no current inhibitor, by centre, ranked by
median usage
N.B: The 95th percentile of units = 6,955 IU kilogram
Figure 9a: This shows factor VIII usage per kilogram per patient by haemophilia centre, ranked by median usage, in patients with severe haemophilia A aged 18 years or more with no reported current inhibitor, and an up-do-date reported bodyweight.
Note that the 95th percentile for adults is lower than for children. This is partly a reflection of the shorter half-life found in small children, who require larger doses per kilogram of bodyweight. The adult outliers also show that a small number of patients, use a great deal of factor VIII, despite having apparently no reported inhibitor in the year. The three extreme outlying users in excess of 15 thousand units per kilogram and a further 46 users in excess of 7 thousand units per kilogram will be the subject of a separate study, to gain a better understanding of the reasons for their unusually high factor usage.
The median treatment intensity range is approximately threefold. There is still a wide range in clinical practice from one centre to the next.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 36
Data table for Figures 9a & b
Haemophilia CentrePatients treated
Patients treated with
weight reported
Total UnitsMedian Units
Median Units/Kg
Aberdeen 14 11 3,914,000 290,000 2,896
Belfast Adults' 46 41 10,088,750 224,000 2,583
Birmingham 73 54 15,415,000 200,500 2,036
Bristol 31 20 7,509,000 185,000 2,340
Cambridge 30 30 8,615,250 259,000 3,222
Canterbury 21 12 7,130,500 336,000 4,089
Cardiff 33 31 5,535,270 156,000 1,504
Coventry 12 12 2,618,500 226,500 3,165
Dundee 14 14 3,392,500 273,250 3,115
Edinburgh 22 22 8,035,000 281,000 3,856
Glasgow 43 43 11,802,500 245,000 2,938
Hammersmith 27 24 9,405,000 336,000 4,712
Kingston upon Hull 15 11 5,076,750 320,000 3,692
Leeds 38 33 14,878,500 360,000 4,276
Leicester 22 19 4,635,944 210,097 2,680
Liverpool 29 15 8,543,500 200,000 3,076
Manchester 79 69 18,674,750 239,500 2,829
Newcastle upon Tyne 42 39 12,920,250 285,000 3,061
North Hampshire 51 44 13,855,430 258,000 3,068
Nottingham 30 30 6,274,500 212,750 2,487
Oxford 97 92 22,705,900 239,000 2,836
Royal Free 135 130 45,621,641 326,000 4,186
Royal London 50 37 10,209,089 185,704 2,645
Sheffield 21 20 8,014,500 345,500 4,070
Southampton 14 10 3,466,500 176,000 2,944
St George's 32 29 4,943,250 144,000 1,819
St Thomas' 104 51 36,071,500 344,000 4,105
Centres with <=4 patients meeting criteria 35 26 9,390,250 220,000 3,117
Centres with 5‐9 patients meeting criteria 32 13 8,907,500 209,250 2,655
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 37
Figure 9b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged 18 years or more with no current inhibitor, by centre, ranked by median
usage per patient
N.B: The 95th percentile of units = 573,000 IU
Figure 9b: This shows usage per patient aged 18 years or more by centre, for patients with severe haemophilia A with no reported current inhibitor not corrected for bodyweight. It shows a wide range in treatment intensity and interpretation is similar to the previous figure, though the sample size is larger since all patients are included and not just those for whom current bodyweight is known.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 38
Figure 10 Median factor VIII units issued per kilogram body weight per year in patients with severe haemophilia A without inhibitors by age
Weight data are missing for 288/1781 patients
Figure 10: This shows the median factor VIII usage per kilogram bodyweight per year in UK patients with severe haemophilia A without inhibitors, broken down by age.
The most intensive general usage appears to be in children, as would be expected. Vial size is also an issue for small children since doses will often be rounded up because the range of available vial sizes does not make it possible to make small dose-adjustments in very small individuals.
Treatment intensity (IU/kg/year) appears to be relatively similar in all adult age-groups.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 39
Figure 11 Median factor VIII units issued (IU/kg) in patients with severe haemophilia A without inhibitors aged 16 and over, by bodyweight
Weight data are missing for 223/1252
Figure 11: This shows median units per kilogram per year issued to UK patients with severe haemophilia A aged 16 and over without inhibitors, broken down by bodyweight. The total number of patients in each group is indicated by the number over each box. Since factor VIII recovery increases progressively as Body Mass Index (BMI) increases, one would expect factor VIII consumption per kilogram bodyweight to decline as bodyweight increases. This appears to be the case generally.
We presume that the `greater than 100 kg’ group will all be obese but since we do not record height, we cannot calculate BMI.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 40
Figure 12 Patients with severe haemophilia A with no current inhibitor in the reporting year: median usage by inhibitor history
Mann-Whitney U test: Under 18 years: p<0.005 (significant); 18 years and over: p=0.03 (significant)
Figure 12: This shows median usage of factor VIII for UK patients with severe haemophilia without a current inhibitor. Usage is broken down by age (less than 18 years, and 18 years and older) and history of FVIII inhibitors. The number of subjects in each group is indicated by the number over each box.
This shows that children with a history of factor VIII inhibitors use significantly more factor VIII than those without such a history. The small difference seen between non-inhibitor and ex-inhibitor adults is also statistically significant (Mann-Whitney U test p<0.005 for children, and p=0.03 for adults). Whilst there are a number of possible explanations for this, it is suspected that reportedly “tolerant” ex-inhibitor patients will commonly have a relatively reduced half-life and low-level circulating factor VIII inhibitors, below the limit of detection of the current Bethesda assay, which are very gradually abolished by ongoing factor VIII prophylaxis.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 41
Table 7 Products issued to treat haemophilia A (including inhibitors), 2017/18
2016/17 2017/18
Bayer Kogenate 19,542,086 11,569,000
Biotest Haemoctin 336,000 392,000
FVIII 8Y 221,510 127,590
Optivate 4,500,425 3,841,220
Helixate Nexgen 24,401,450 13,065,000
Riastap (g) 3 6
Alphanate 114,000 111,000
Fanhdi 19,616,500 14,553,040
NovoSeven (mg) 19,700 18,649
NovoEight ‐ 13,586,150
Nuwiq 6,013,280 10,922,016
Octanate 5,086,500 4,263,500
Wilate ‐ 6,000
Pfizer ReFacto AF 284,693,866 255,426,658
Roche Emicizumab (EAMS) (mg) ‐ 15,081
Advate 175,084,058 171,523,660
FVII ‐ 45,000
FEIBA 35,104,000 30,234,596
SOBI/Biogen Elocta 15,257,316 69,454,048
Desmopressin 23,767 29,394
Investigational Factor VIII 10,573,777 5,807,522
Investigational Factor VII * *
Other Investigational
Products * *
Various Manufacturers
Total Units Manufacturer Product
BPL
Shire
CSL Behring
Novo Nordisk
Octapharma
Grifols
Units in IU unless otherwise stated * Due to commercial sensitivities, units have been withheld
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 42
Table 7: This shows a breakdown of products, listed by supplier, issued to treat UK patients with haemophilia A in 2017/18, including those with inhibitors but excluding acquired haemophilia.
These figures have been cross-checked against sales figures supplied by the manufacturers for the same period. Whilst one would not expect a perfect match between NHD figures and the manufacturer’s sales figures, there is a very high level of correlation for all but the low usage products. These sales figures are not reported by agreement with suppliers for reasons of commercial sensitivity.
By and large, the plasma derived products listed were used for immune tolerance induction. The exception, Fanhdi, is also used for a group of patients without inhibitors attending a single centre in the South of England. The usage of Fanhdi has declined in the last three years.
The use of investigational factor VIII continues to decline as several clinical trials come to an end, so it is likely that the use of investigational factor VIII may decline further from its recent historic high. We have deliberately aggregated and anonymised investigational products to avoid any breach of individual centre’s confidentiality agreements and to take account of commercial sensitivities.
Emicizumab (Hemlibra®) is listed for the first time, having previously been unlicensed. This product became available on prescription in July for inhibitor patients and usage is expected to increase.
Tab
le 8
F
acto
r V
III u
nits
issu
ed b
y U
K h
aem
ophi
lia c
entr
es, b
y di
agno
sis.
201
7/18
Plasma
Recombina
ntInve
stigationa
lEn
hanced
Half‐
Life
Total
Hae
mophilia A
3,152
23,294,350
476,092,484
5,807,522
69,454,048
574,648,404
Acquired Hae
mophilia A
9
7,600
70,000
‐
‐
77,600
von W
illebrand disease
784
22,054,403
207,000
‐
‐
22,261,403
Acquired von W
illebrand Disease
34
980,500
3,000
‐
‐
983,500
Platelet‐type Pseudo von W
illebrand Disease
2
5,000
‐
‐
‐
5,000
Probab
le von W
illebrand disease
1
2,000
‐
‐
‐
2,000
F.V deficiency
1
‐
39,000
‐
‐
39,000
F.VII deficiency
1
‐
1,250
‐
‐
1,250
Combined V+V
III D
eficiency
11
‐
61,000
‐
‐
61,000
Co‐inherited diagn
oses
26
405,900
573,500
‐
593,000
1,572,400
Miscellan
eous
5
118,060
‐
‐
‐
118,060
Total
4,026
46,867,813
477,047,234
5
,807,522
70,047,048
599,769,617
FVIII (IU)
Coagulation De
fect
Patie
nts
Trea
ted
Pro
duct
s co
ntai
ning
VW
F a
s w
ell a
s F
VIII
are
rep
orte
d in
FV
III u
nits
Tabl
e 8:
T
his
show
s fa
ctor
VIII
con
cent
rate
use
bro
ken
dow
n ac
cord
ing
to d
iagn
osis
tre
ated
, in
clud
ing
appa
rent
ly a
nom
alou
s us
e re
port
ed
to t
he N
HD
. P
rodu
cts
used
to
trea
t vo
n W
illeb
rand
dis
ease
whi
ch in
clud
e V
WF
and
FV
III a
re in
clud
ed a
nd a
re r
epor
ted
in F
VIII
uni
ts.
It
is
perh
aps
surp
risin
g th
at s
uch
a la
rge
amou
nt o
f re
com
bina
nt f
acto
r V
III w
as u
sed
for
the
trea
tmen
t of
von
Will
ebra
nd d
isea
se,
give
n th
at it
co
ntai
ns n
o vo
n W
illeb
rand
fact
or.
Mor
e de
tail
on th
e us
e of
thes
e pr
oduc
ts to
trea
t VW
D is
giv
en w
ith ta
ble
16.
* P
oten
tially
ano
mal
ous
use
of fa
ctor
VIII
in T
able
8 is
acc
ount
ed fo
r as
follo
ws:
FV
Def
icie
ncy:
Pat
ient
with
FV
def
icie
ncy
deve
lope
d a
mild
inhi
bito
r po
st-p
artu
m a
nd w
as d
iagn
osed
with
Acq
uire
d H
aem
A.
Mis
cella
neou
s bl
eedi
ng d
isor
ders
: th
rom
botic
thro
mbo
cyto
peni
a pu
rpur
a.
Page | 43
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Baye
r -Re
com
bina
nt
1.93
%
Biot
est -
Plas
ma
0.07
%
BPL -
Plas
ma
0.68
% CSL B
ehri
ng -
Plas
ma
2.65
%CS
L Beh
ring
-Re
com
bina
nt
2.19
%G
rifo
ls -
Plas
ma
2.53
%
Nov
o N
ordi
sk -
Reco
mbi
nant
2.
27%
Oct
apha
rma
-Pla
sma
1.89
%
Oct
apha
rma
-Re
com
bina
nt
1.82
%
Pfize
r -Re
com
bina
nt
42.6
1%
Shir
e -R
ecom
bina
nt
28.7
2%
SOBI
/Bio
gen
-Enh
ance
d H
alf-L
ife
11.6
8%In
ves�
ga�o
nal r
FVIII
0.
97%
Figu
re 1
3 M
arke
t Sha
re o
f fac
tor V
III c
once
ntra
tes
issu
ed b
y U
K h
aem
ophi
lia c
entre
s, 2
017/
18
Man
uact
urer
-Pro
duct
Typ
ePa
tient
s(n
)
Baye
r - R
ecom
bina
nt13
1
Bi
otes
t - P
lasm
a1
BP
L - P
lasm
a15
CSL B
ehrin
g - P
lasm
a60
1
CS
L Beh
ring
- Rec
ombi
nant
134
Grifo
ls - P
lasm
a57
Nov
o N
ordi
sk -
Reco
mbi
nant
237
Oct
apha
rma
- Pla
sma
260
Oct
apha
rma
- Rec
ombi
nant
57
Pfi
zer -
Rec
ombi
nant
1,49
8
Shire
- Re
com
bina
nt1,
181
SO
BI/B
ioge
n - E
nhan
ced
Half-
Life
404
Inve
s�ga�o
nal r
FVIII
47
To
tal
4,62
3
Figu
re 1
3: T
his
show
s th
e m
arke
t bre
akdo
wn
of
fact
or V
III c
once
ntra
tes
issu
ed fo
r all
diag
nose
s,
incl
udin
g in
hibi
tor
patie
nts.
Pla
sma-
deriv
ed
fact
or V
III is
gen
eral
ly u
sed
for t
reat
men
t of v
on
Will
ebra
nd d
isea
se o
r fo
r im
mun
e to
lera
nce
indu
ctio
n, b
ut o
ne c
entre
has
a s
igni
fican
t us
e of
Fa
nhdi
fo
r no
n-in
hibi
tor
patie
nts
with
ha
emop
hilia
A a
nd o
ne o
r tw
o ot
her
isol
ated
pa
tient
s in
oth
er c
entre
s us
e pl
asm
a-de
rived
pr
oduc
ts a
s th
eir r
outin
e re
plac
emen
t the
rapy
.
| egaP 44
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 45
2.2 Haemophilia B
Tab
le 9
P
atie
nts
with
con
geni
tal h
aem
ophi
lia B
(in
clud
ing
carr
iers
) re
gist
ered
and
trea
ted,
201
7/18
MF
Total
MF
Total
MF
Total
MF
Total
MF
Total
MF
Total
<18 years
122 ‐
122 81 ‐
81
100 59 159 5
34
39
‐ ‐
‐
308 93 401
≥18 years
237 1 238 255 5 260 395 219 614 37 239 276 1
5
6
925 469 1,394
Total
359 1
360 336 5 341 495 278 773
4
2 273 315
1 5
6 1,233 562
1,795
<18 years
8
‐
8
5
‐
5
8
10
18
1
8
9
‐ ‐
‐
22 18
40
≥18 years
2
‐
2
4
‐
4
9
6
15
2
20
22
‐ ‐
‐
17 26
43
Total
1
0 ‐ 10
9 ‐
9 1
7 1
6 3
3 3 28
3
1 ‐ ‐
‐ 3
9 4
4 8
3
<18 years
113 ‐
113 43 ‐
43
30 5
35
‐ ‐
‐
‐ ‐
‐
186 5 191
≥18 years
224 ‐
224 134 1 135 110 29 139 6
6
12
1
‐
1
475 36 511
Total
337 ‐
337 177 1 178 140 3
4 174 6 6
1
2 1 ‐
1 661 41
702
<18 years
109 ‐
109 42 ‐
42
30 5
35
‐ ‐
‐
‐ ‐
‐
181 5 186
≥18 years
217 ‐
217 134 1 135 110 28 138 6
5
11
1
‐
1
468 34 502
Total
326 ‐
326 176 1 177 140 3
3 173 6 5
1
1 1 ‐
1 649 39
688
Total In Register
New Registrations *
Treated in
year**
Treated with
concentrate in
year**
Hae
mop
hilia
B
Age
Ra
nge
Num
ber o
f Patients (Factor IX
leve
l (IU/dl))
< 1
1 ‐ 5
>5 & <40
≥ 40
Unk
nown
Total
* N
ew re
gist
ratio
ns a
re a
sub
set o
f the
‘In
Reg
iste
r’ nu
mbe
rs
** T
reat
ed in
clud
es p
atie
nts
‘In R
egis
ter’
and
‘New
Reg
istr
atio
ns’
Tabl
e 9:
T
his
show
s th
e nu
mbe
r of
pat
ient
s w
ith h
aem
ophi
lia B
(in
clud
ing
carr
iers
and
def
icie
nt f
emal
es),
bro
ken
dow
n by
sev
erity
, ge
nder
an
d ag
e.
Pat
ient
s ne
wly
reg
iste
red
are
also
sho
wn,
as
are
the
num
bers
tre
ated
. T
he n
umbe
r of
reg
iste
red
patie
nts
with
hae
mop
hilia
B
cont
inue
s to
ris
e, e
spec
ially
non
-sev
ere
haem
ophi
lia B
, whi
ch m
ay p
revi
ousl
y ha
ve b
een
unde
rdia
gnos
ed.
Page | 46
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 47
Figure 14 Carriers of haemophilia B currently registered and newly registered, by baseline factor IX level, 2017/18
0
20
40
60
80
100
120
140
160
<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/K
1
12
40
86
129
104
142
40 0 16 9 12
16
0
Patien
ts (n
)
Factor FIX level (IU/dl)
Haemophilia B CarrierIn Register
(excl. new registrations)
Haemophilia B CarrierNew Registrations
<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/KGrand Total
Haemophilia B Carrier
In Register
(excl. new registrations)
1 12 40 86 129 104 142 4 518
Haemophilia B Carrier
New Registrations0 0 1 6 9 12 16 0 44
Total 1 12 41 92 138 116 158 4 562
Diagnosis Number of Patients (Factor IX level (IU/dl))
N.B: Includes carrier of haemophilia B and females with FIX deficiency
Figure 14: This shows the distribution of reported factor IX levels amongst registered carriers of haemophilia B in the UK. Carriers with normal factor IX levels are still under-represented because these were not registered until relatively recently. All carriers should be registered.
It is interesting that there is a relatively large number of very low-level carriers. These mostly have an extreme degree of lyonisation but some are homozygous products of consanguineous unions. In some cases, the level is not known to us, either because the patient is too young to be tested or because a test result has been inadvertently omitted.
Tab
le 1
0 N
ew r
egis
trat
ions
of h
aem
ophi
lia B
(in
clud
ing
carr
iers
), b
y ag
e at
mid
-yea
r, g
ende
r an
d se
verit
y, 2
017/
18
Hae
mop
hilia
B MF
Total
MF
Total
MF
Total
MF
Total
MF
Total
0 ‐ < 2
8
‐
8
5
‐
5
2
2
4
1
2
3
16
4
20
2 : 4
‐
‐
‐
‐
‐
‐
2
1
3
‐
‐
‐
2
1
3
5 : 9
‐
‐
‐
‐
‐
‐
2
3
5
‐
4
4
2
7
9
10 : 19
1
‐
1
‐
‐
‐
2
4
6
1
4
5
4
8
12
20 : 29
‐
‐
‐
2
‐
2
2
‐
2
1
4
5
5
4
9
30 : 39
‐
‐
‐
1
‐
1
4
1
5
‐
5
5
5
6
11
40 : 49
‐
‐
‐
1
‐
1
1
1
2
‐
‐
‐
2
1
3
50 : 59
1
‐
1
‐
‐
‐
‐
1
1
‐
3
3
1
4
5
60 : 69
‐
‐
‐
‐
‐
‐
2
1
3
‐
4
4
2
5
7
70 +
‐
‐
‐
‐
‐
‐
‐
2
2
‐
2
2
‐
4
4
Total
100
109
09
1716
333
2831
3944
83
Total
Num
ber o
f Patients (Factor IX
leve
l (IU/dl))
Age
(yea
rs)
< 1
1 ‐ 5
> 5 & < 40
≥ 40
Tabl
e 10
: T
his
show
s ne
w r
egis
trat
ions
of h
aem
ophi
lia B
bro
ken
dow
n by
rep
orte
d se
verit
y an
d ag
e at
mid
-yea
r ye
ar (
30/0
9/20
17).
The
two
patie
nts
with
sev
ere
dise
ase
regi
ster
ed a
fter
the
age
of t
wo
wer
e bo
rn o
utsi
de t
he E
U.
Les
s se
vere
dis
ease
will
ofte
n pr
esen
t at
a la
ter
age
and
we
have
not
inve
stig
ated
the
prop
ortio
n of
that
gro
up w
hich
is n
ativ
e to
the
UK
.
Page | 48
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 49
Figure 15a Trend in numbers of severe haemophilia B patients aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)
N.B. Carriers are included in Figures 15a – 15c
Figure 15a: This shows the trend in numbers of patients aged over 60 years with severe haemophilia B since 1977. This shows a fourfold increase over the past 40 years, presumably attributable to increased life-expectancy.
Figure 15b (overleaf): This shows a similar bar diagram of patients with moderate severity haemophilia B showing an almost fourfold increase in patients aged over 60 years with moderate severity haemophilia B during the past 40 years. This will reflect a combination of better diagnosis, more complete registration and improved life expectancy.
Figure 15c (overleaf): This shows the trend in numbers of patients aged over 60 years with mild haemophilia B in the register since 1977. This shows an approximately twelve-fold increase over the past 40 years. This probably reflects a relatively modest increase in life expectancy coupled with increased diagnosis and reporting of mild haemophilia B.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 50
Figure 15b Trend in numbers of moderate haemophilia B patients aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)
Figure 15c Trend in numbers of mild haemophilia B patients aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)
Figu
re 1
6 Fa
ctor
IX u
nits
issu
ed b
y U
K h
aem
ophi
lia c
entre
s to
trea
t hae
mop
hilia
B, 1
993
– 201
7/18
Figu
re 1
6: S
how
s U
K fa
ctor
IX u
sage
for a
ll di
agno
ses
from
199
3 to
201
7/18
. Th
e nu
mbe
r of p
atie
nts
repo
rted
to h
ave
been
trea
ted
is s
how
n by
the
blue
line
usi
ng a
sec
onda
ry a
xis.
Use
of r
ecom
bina
nt S
HL
FIX
red
uced
by
29%
bet
wee
n 20
16/1
7 an
d 20
17/1
8 an
d us
e of
EH
L FI
X
(sho
wn
in g
reen
) inc
reas
ed b
y 32
0% in
the
sam
e pe
riod.
Ove
rall,
fact
or IX
con
sum
ptio
n ha
s de
clin
ed a
s a
dire
ct c
onse
quen
ce o
f the
gra
dual
in
trodu
ctio
n of
EH
L FI
X p
rodu
cts,
whi
ch a
re p
resc
ribed
gen
eral
ly in
low
er d
oses
/kg/
wee
k th
an s
tand
ard
prod
ucts
.
| egaP 15
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
0100
200
300
400
500
600
700
800
0102030405060708090100
Pa�ents (n)
Units(millions)
Tim
e Pe
riod
Plas
ma
Reco
mbi
nant
Inve
s�ga�o
nal
EHL
Pa�e
nts t
reat
ed
Tab
le 1
1 F
acto
r IX
usa
ge b
y re
gion
for
patie
nts
with
sev
ere
haem
ophi
lia B
(in
cl. t
reat
men
t for
inhi
bito
rs a
nd E
HL-
IX),
201
7/18
Region
Gen
eral
Popu
latio
n
Patie
nts
trea
ted
(n)
Total FIX
(IU)
Mea
n Usage
FIX Units
Per C
apita
South W
est
5,559,316
163,742,500
233,906
0.67
London
8,825,001
5711,911,676
208,977
1.35
North W
est
7,258,627
295,709,250
196,871
0.79
Yorkshire and the Humber
5,450,130
264,898,900
188,419
0.90
West M
idlands
5,860,706
274,837,350
179,161
0.83
South East
9,080,825
569,578,358
171,042
1.05
East of En
glan
d6,168,432
386,454,065
169,844
1.05
North East
2,644,727
111,709,750
155,432
0.65
East M
idlands
4,771,666
253,586,613
143,465
0.75
Englan
d55,619,430
285
52,428,462
183,960
0.94
Northern Ireland
1,870,834
81,732,500
216,563
0.93
Scotlan
d East
3,051,000
121,493,250
124,438
0.49
Scotlan
d W
est
2,373,800
121,347,838
112,320
0.57
Wales
3,125,165
91,296,500
144,056
0.41
United King
dom
66,040,229
326
58,298,550
178,830
0.88
Seve
re Hae
mop
hilia
B
Eng
lish
regi
ons
rank
ed b
y m
ean
usag
e
Sou
rce
accr
edita
tion:
Pop
ulat
ion
Est
imat
es fo
r UK
, Eng
land
and
Wal
es, S
cotla
nd a
nd N
orth
ern
Irel
and:
Mid
-201
7: O
ffice
for N
atio
nal S
tatis
tics
licen
sed
unde
r the
Ope
n G
over
nmen
t Lic
ence
v.3
.0.
© C
row
n co
pyrig
ht 2
018
Mid
-201
7 po
pula
tion
estim
ates
Sco
tland
sup
plie
d by
Nat
iona
l Rec
ords
of S
cotla
nd u
nder
the
Ope
n G
over
nmen
t Lic
ence
v3.
0 ©
Cro
wn
Cop
yrig
ht 2
018
NO
TE
: Pat
ient
s ar
e al
loca
ted
to e
ach
regi
on b
ased
on
thei
r ho
me
post
code
, rat
her t
han
whe
re th
ey w
ere
trea
ted
Page | 52
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 53
Table 11 (previous page): This shows factor IX usage by commissioning region. This shows similar variation in treatment intensity to that observed with haemophilia A, although patient numbers for this diagnosis are very much smaller and so between-region comparisons of treatment intensity cannot really be made. Although usage per patient in Northern Ireland appears higher than elsewhere in the UK, no reasonable comparison can be made given that only eight patients with haemophilia B are treated in the province and there is considerable interpersonal variation in clinical phenotype for this condition.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 54
Table 12 Products issued to treat haemophilia B (including inhibitors), 2017/18
2016/17 2017/18
Biotest Haemonine ‐ 46,000
BPL Replenine 2,548,450 910,985
IDELVION 1,030,500 5,938,750
Mononine 362,000 78,000
Grifols Alphanine 5,876,000 4,748,000
Novo Nordisk NovoSeven (mg) 10,391 9,197
Pfizer BeneFIX 77,093,592 53,637,050
FEIBA 1,652,000 1,818,000
RIXUBIS 223,000 985,000
SOBI/Biogen ALPROLIX 3,303,013 12,136,054
Various Manufacturers Investigational Factor IX 2,420,676 260,074
CSL Behring
Manufacturer Product Total Units
Shire
Units in IU unless otherwise stated
Table 12: This gives a breakdown of the products issued to treat haemophilia B in the UK in 2016/17 and 2017/18, organised by supplier. These figures have been cross-checked with sales figures provided by the suppliers. Whilst we would not expect a perfect match between manufacture's sales figures and NHD usage figures, there was a high level of correlation except for low-usage products. Sales figures are not reported for reasons of confidentiality.
Note the continued marked reduction in the proportion of investigational factor IX use as clinical trials come to an end. We have deliberately aggregated and anonymised investigational products to avoid any breach of confidentiality agreements and to take account of commercial sensitivities. We are unable to distinguish between standard and extended half-life investigational products for that reason. We would advise that data on trial products should be shared at a local level with commissioners so that they have a realistic estimate of future product consumption and avoid any inadvertent reduction in future budget. A significant proportion of FIX used was plasma-derived, mainly for patients who do not “get on with” BeneFIX. The proportions of plasma-derived FIX supplied by BPL, CSL and Grifols have all declined, with patients switching to EHL FIX.
Tab
le 1
3 F
acto
r IX
uni
ts is
sued
by
UK
hae
mop
hilia
cen
tres
, by
diag
nosi
s, 2
017/
18
Plasma
Recombina
ntInve
stigationa
lEn
hanced
Half‐
Life
Total
Hae
mop
hilia
B688
5,782,985
54,622,050
260,074
18,074,804
78,739,913
Unclassified blee
ding
disorde
r1
‐
1,500
‐
‐
1,500
Total
68
9 5
,782,985
54,623,550
260,074
18,074,804
78,741,413
FIX (IU
)Co
agulation De
fect
Patie
nts
Trea
ted
Tabl
e 13
: T
his
show
s U
K f
acto
r IX
issu
ed in
201
7/18
, br
oken
dow
n by
pro
duct
typ
e an
d di
agno
sis.
N
ote
that
thi
s in
clud
es t
he u
se o
f ov
er
260,
000
units
of i
nves
tigat
iona
l rec
ombi
nant
fact
or IX
. T
his
repr
esen
ts a
sm
alle
r pro
port
ion
of th
e to
tal F
IX u
nits
issu
ed c
ompa
red
to la
st y
ear.
* P
oten
tially
ano
mal
ous
use
of fa
ctor
IX in
Tab
le 1
3 is
acc
ount
ed fo
r as
follo
ws:
Unc
lass
ified
ble
edin
g di
sord
er: P
atie
nt h
as s
ince
bee
n re
-reg
iste
red
as h
aem
ophi
lia B
and
will
be
repo
rted
as
such
in th
e ne
xt r
epor
t.
Page | 55
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Figu
re 1
7 M
arke
t Sha
re o
f fac
tor I
X c
once
ntra
tes
issu
ed b
y U
K h
aem
ophi
lia c
entre
s, 2
017/
18
Figu
re 1
9 Th
is s
how
s th
e m
arke
t bre
akdo
wn
of fa
ctor
IX c
once
ntra
tes.
| egaP 65
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Man
uact
urer
-Pro
duct
Typ
ePa
tient
s(n
)
Biot
est -
Pla
sma
1BP
L - P
lasm
a5
CSL B
ehrin
g - P
lasm
a2
CSL B
ehrin
g - E
nhan
ced
Half-
Life
73Gr
ifols
- Pl
asm
a19
Pfize
r - R
ecom
bina
nt56
0Sh
ire -
Reco
mbi
nant
9SO
BI/B
ioge
n - E
nhan
ced
Half-
Life
110
Inve
s�ga�o
nal R
ecom
bina
nt F
IX10
Tota
l78
9
Pfize
r -Re
com
bina
nt68
.12%
Shir
e -R
ecom
bina
nt1.
25%
Gri
fols
-Pl
asm
a6.
03%
BPL -
Plas
ma
0.06
%
CSL
Behr
ing -
Plas
ma
1.16
%
Biot
est -
Plas
ma
0.10
%
SOBI
/Bio
gen
-En
hanc
ed H
alf-L
ife15
.41%
CSL
Behr
ing -
Enha
nced
H
alf-L
ife7.
54%
Inve
s�ga
�ona
l Re
com
bina
nt F
IX0.
33%
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 57
2.3 Von Willebrand Disease
Tab
le 1
4 P
atie
nts
with
von
Will
ebra
nd d
isea
se r
egis
tere
d an
d tr
eate
d A
pril
2017
- M
arch
201
8
<10
10 ‐ 2
9 ≥30
N/K
Sub
To
tal
<10
10 ‐ 2
9 ≥30
N/K
Sub
To
tal
Type 1
25173
268
11477
80362
632
921,166
1,643
7534
Type 2A
3834
60
7896
7336
3208
286
695
Type 2B
69
50
2015
3515
267
8722
1Type 2M
179
30
2927
3510
375
104
183
Type 2N
10
30
43
223
432
365
0Type 2 Unspecified
58
50
1812
149
136
549
0Type 3
2661
8764
0Type Unreported
59132
234
7432
159
328
594
531,134
1,566
8933
Low VWF
01
200
210
039
039
600
0
Sub To
tal M
ales
3,923
351
76
Type 1
24121
197
4346
128
600
1,704
188
2,620
2,966
111
97Type 2A
2629
120
67120
110
664
300
367
7613
Type 2B
79
80
2414
4640
1101
125
260
Type 2M
923
40
3650
7018
4142
178
298
Type 2N
01
30
45
961
479
8314
0Type 2 Unspecified
44
10
918
2716
162
7111
1Type 3
1954
7346
0Type Unreported
59134
197
7397
210
610
1,553
150
2,523
2,920
129
73Low VWF
00
130
130
079
079
920
1Su
b To
tal Fem
ales
6,875
442
1
93
Grand
Total ‐ Males and
Fem
ales
10,798
793
2
69
2661
1954
Treated
with
De
smop
ressin
Fem
ales
Males
von
Willeb
rand
disease
<18 yea
rs
≥18 yea
rs
Total
Treated
with
Co
ncen
trate
VWD Ac
tivity
IU/dl
Page | 58
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 59
Table 14: This shows patients registered with von Willebrand disease broken down by age, activity level, subtype, gender and treatment. The Annual Report review meeting suggested that, whilst there is no generally agreed severity classification for VWD, we report subdivisions from <10, 10-29 and ≥30% VW activity to give some indication of the distribution of severity amongst the UK cohort.
A VW subtype is reported for 58% of patients, almost the same proportion as last year. Efforts are ongoing to tidy up this part of the database, but problems include repeatedly changing classification over time; very old data entries; and changing opinion in relation to the diagnosis of mild type 1 VWD, which may have been over-diagnosed in the past.
There remains an excess of blood group O patients and adult females, reflecting referral bias and possible over-diagnosis of mild type 1 VWD.
Table 15 (overleaf): This shows that 442 new patients with von Willebrand disease were registered in the past year, only 17% of whom were registered without indicating a subtype.
As one would expect, the previously reported relative excess of female registrants only becomes apparent after menarche. New registrations of von Willebrand disease are approximately equally distributed between genders in patients under 18 years of age.
Tab
le 1
5 N
ew R
egis
trat
ions
of v
on W
illeb
rand
dis
ease
bet
wee
n A
pril
2017
& M
arch
201
8, b
y ag
e at
mid
-yea
r, s
ever
ity, a
nd
gend
er
<10
10 ‐ 2
9 ≥30
N/K
Sub
To
tal
<10
10 ‐ 2
9 ≥30
N/K
Sub
To
tal
Type 1
425
391
691
1624
041
110
Type 2A
33
00
61
12
04
10Type 2B
10
10
20
00
00
2Type 2M
00
00
01
40
05
5Type 2N
10
00
10
00
00
1Type 2 Unspecified
02
10
31
01
02
5Type 3
10
1Type Unreported
14
100
151
45
010
25Low VWF
00
20
20
02
02
4
Sub To
tal M
ales
163
Type 1
026
261
533
4176
1121
174
Type 2A
14
20
71
65
012
19Type 2B
03
00
30
11
02
5Type 2M
12
00
30
20
02
5Type 2N
00
20
20
06
06
8Type 2 Unspecified
13
10
50
00
00
5Type 3
32
5Type Unreported
35
60
144
1317
135
49Low VWF
00
20
20
07
07
9
Sub To
tal Fem
ales
279
Grand
Total ‐ Males and
Fem
ales
442
32
Males
Fem
ales
von
Willeb
rand
disease
VWF Ac
tivity
IU/dl
Total
<18 yea
rs
≥18 yea
rs
10
Page | 60
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
0100
200
300
400
500
600
700
800
900
0510152025
Pa�ents (n)
Units(millions)
Tim
e Pe
riod
Plas
ma
Reco
mbi
nant
Pa�e
nts t
reat
ed
Figu
re 1
8 Fa
ctor
VIII
uni
ts is
sued
by
UK
hae
mop
hilia
cen
tres
to tr
eat V
on W
illeb
rand
dis
ease
199
3 – 2
017/
18
In
clud
es p
rodu
cts
cont
aini
ng a
com
bina
tion
of V
WF
and
FVIII
, whi
ch a
re re
porte
d in
FV
III u
nits
Figu
re 1
8: I
n co
ntra
st to
hae
mop
hilia
A a
nd B
, the
incr
easi
ng c
onsu
mpt
ion
of V
W C
once
ntra
tes
sinc
e 19
93 c
lose
ly r
efle
cts
the
incr
easi
ng
num
ber o
f pat
ient
s re
quiri
ng tr
eatm
ent.
The
num
ber o
f pat
ient
s w
ith T
ype
3 V
WD
has
incr
ease
d m
arke
dly
with
the
pass
age
of ti
me.
| egaP 36 | egaP 16
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 62
Table 16 Products issued to treat von Willebrand disease (including inhibitors), 2017/18
2016/17 2017/18
Bayer Kogenate 90,500 13,000
Haemate P 4,387,950 1,673,503
Riastap (g) ‐ 1,000
Voncento 9,118,900 13,002,900
Grifols Alphanate 873,000 494,000
LFB Biomedicaments Willfact /Wilfactin 1,027,000 1,458,000
Novo Nordisk NovoSeven (mg) 1,087 232
Wilate 5,417,904 6,884,000
Octaplex ‐ 1,015
Pfizer ReFacto AF 5,500 12,000
Shire Advate 35,000 182,000
Desmopressin 14,043 15,530
Investigational rVWF * *
Product Total Units
CSL Behring
Manufacturer
Octapharma
*Anonymised for confidentiality purposes Units in IU unless otherwise stated
Products containing VWF and FVIII are reported in FVIII units
Table 16: This shows a breakdown of concentrates issued to treat von Willebrand disease in the UK ordered by supplier. These are generally listed by and priced by their labelled factor VIII content, with the exception of Willfact VWF concentrate (LFB), which is labelled and priced only by its VWF content.
* Potentially anomalous product use in Table 16 is accounted for as follows:
Advate: Allergic to VWF products Advate: Developed an inhibitor Advate: Issued for low FVIII before confirmation of diagnosis Kogenate: Does not respond to typical VW products ReFacto AF: centre confirmed usage ReFacto AF: Entered in error, now corrected
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 63
2.4 Inhibitors: Congenital and Acquired
Tab
le 1
7 In
hibi
tors
by
dise
ase
seve
rity
– hae
mop
hilia
A, h
aem
ophi
lia B
& v
on W
illeb
rand
dis
ease
< 1
2,014
16(0.8)
150(7.4)
297(14.7)
463(23.0)
1 ‐ 5
818
4(0.5)
31(3.8)
48(5.9)
83(10.1)
>55,327
3(0.1)
15(0.3)
37(0.7)
55(1.0)
Total
8,159
23(0.3)
196(2.4)
382(4.7)
601(7.4)
Seve
re360
0(0.0)
11(3.1)
6(1.7)
17(4.7)
Non
‐Sev
ere
1,435
0(0.0)
0(0.0)
0(0.0)
0(0.0)
Total
1,795
0(0.0)
11(0.6)
6(0.3)
17(0.9)
Type
14,609
0(0.0)
0(0.0)
1(0.0)
1(0.0)
Type
3160
0(0.0)
6(3.8)
1(0.6)
7(4.4)
Others
6,030
0(0.0)
0(0.0)
0(0.0)
0(0.0)
Total
10,799
0(0.0)
6(0.1)
2(0.0)
8(0.1)
Coagulation De
fect
Seve
rity (
IU/dl)
/ Sub
type
Hae
mop
hilia
A
Hae
mop
hilia
B
Von
Willeb
rand
disea
se
In Reg
ister *
Inhibitors n (%
)
Newly
Repo
rted
Ongo
ing
Historica
lTo
tal
*
Incl
udin
g pa
tient
s no
t reg
ular
ly tr
eate
d N
ew=n
ewly
repo
rted
in y
ear
Ong
oing
=inh
ibito
r in
year
but
not
new
in y
ear
His
toric
al=h
isto
ry o
f inh
ibito
r, b
ut n
ot c
urre
nt
Page | 64
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 65
Table 17: This table shows the incidence of new inhibitors in the past year, the prevalence of inhibitors ever registered and the prevalence of those still considered active for haemophilia A, B and von Willebrand disease, broken down by disease severity.
Those labelled “new” were reported for the first time in the year 2017/18. Those labelled “ongoing” are those reported in previous years which have not been eradicated and which remain clinically significant. Those reported as “historical” are those reported to have been eradicated or disappeared and not ongoing.
This shows that an history of inhibitor is over twice as prevalent in severe than in moderate haemophilia A and twenty times more prevalent than in mild haemophilia A. The proportion of patients with non-severe haemophilia A, thought to have eliminated their inhibitor cannot be known with certainty, however, since some may have an undetectable inhibitor which may reappear as soon as they have factor VIII replacement. Similarly, many “ex inhibitor” patients with severe haemophilia probably continue to have some low-level inhibitor activity, below the level of detection of the Bethesda assay.
Inhibitors in haemophilia B are, fortunately, far less common, with a prevalence of 0.9% of patients registered with haemophilia B. These arise early in the patient’s treatment history and only in severe haemophilia B.
Inhibitors in von Willebrand disease appear in our cohort mainly in type 3 VWD and judged by the very low number of historical inhibitors reported (1 of 7), are very difficult to eradicate.
Table 18 (overleaf): Shows reported product use for UK patients with a current inhibitor during 2017/18, broken down by diagnosis and supplier. All product usage for these patients in that year is shown.
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
Page | 66
Table 18 Products issued to patients with congenital bleeding disorders reported to have a positive inhibitor during 2017/18
Bayer Kogenate 1,024,000 4
FVIII 8Y 127,590 1
Optivate 3,469,220 4
Helixate Nexgen 1,355,250 3
Riastap (mg) 6 1
Grifols Fanhdi 1,567,040 8
NovoSeven (mg) 18,642 91
NovoEight 151,000 4
Nuwiq 3,805,250 6
Octanate 3,281,500 6
Pfizer ReFacto AF 13,205,681 37
Roche Emicizumab (EAMS) 13,881 17
Advate 16,208,500 41
FEIBA 30,181,596 81
SOBI/Biogen Elocta 2,953,000 13
Desmopressin 94 2
Investigational FVII 3 1
Investigational FVIII mimetic 25,895 11
Investigational FVIII 451,466 5
Novo Nordisk NovoSeven (mg) 9,197 10
Shire FEIBA 1,818,000 4
Haemate P 76,000 1
Voncento 386,300 4
Novo Nordisk NovoSeven (mg) 214 4
Shire Advate 137,000 1
Novo Nordisk NovoSeven (mg) 1,314 1
Novo Nordisk NovoSeven (mg) 89 1
Novo Nordisk NovoSeven (mg) 126 2
Roche Emicizumab (EAMS) 900 1
Shire FEIBA 1,408,000 2
Desmopressin 30 1
CSL Behring
F.VII deficiency
Co‐inherited diagnoses
Various Manufacturers
von Willebrand Disease
F.XI deficiency
Manufacturer Product
Haemophilia B
Haemophilia A
Shire
BPL
Units Patients
CSL Behring
Novo Nordisk
Octapharma
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Table 19 Products issued to patients with Acquired Inhibitors 2017/18
ManufacturerProduct /
Patients (n)Acquired
Haemophilia AAcquired
von WillebrandsAcquired
Deficiency ‐ Other
Bayer FVIII 8Y (n= 1) 4,000 ‐ ‐
Haemate P (n= 4) ‐ 75,500 ‐
Riastap (g) (n= 2) 2,006 ‐ ‐
Voncento (n= 19) 3,600 753,500 ‐
Novo Nordisk NovoSeven (mg) (n= 25) 5,634 ‐ ‐
Octaplex (n= 1) 2,000 ‐ ‐
Wilate (n= 13) ‐ 151,500 ‐
Pfizer ReFacto AF (n= 6) 14,000 3,000 ‐
Advate (n= 4) 56,000 ‐ ‐
FEIBA (n= 80) 7,797,500 ‐ ‐
Desmopressin (n= 3) 15 144 30
CSL Behring
Octapharma
Shire
Units in IU unless otherwise stated
Table 19: This shows reported product use for UK patients with an acquired inhibitor reported or ongoing during 2017/18, broken down by diagnosis and supplier.
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Table 20 FEIBA® usage: breakdown by diagnosis
Coagulation DefectNumber of Patients
Total(u)
Haemophilia A 84 30,234,596
Haemophilia B 4 1,818,000
F.V deficiency 1 64,000
Acquired Haemophilia A 80 7,797,500
Co‐inherited diagnoses 2 1,408,000
Total 171 41,322,096
Table 21 NovoSeven® usage: breakdown by diagnosis
Coagulation DefectNumber of Patients
Total(mg)
Haemophilia A 92 18,649
Haemophilia B 10 9,197
von Willebrand disease 6 232
Acquired Haemophilia A 25 5,634
F.V deficiency 1 18
F.VII deficiency 64 3,206
F.XI Deficiency 2 124
Co‐inherited diagnoses 2 126
Bernard Soulier 10 185
Glanzmann's Thrombasthenia 46 5,457
Platelet defects 2 40
Unclassified bleeding disorder 2 20
262 42,888
Tables 20 & 21: These show in greater detail how much FEIBA® and NovoSeven® were issued for each diagnosis in 2017/18. Patients with any hereditary or acquired bleeding disorder, either with or without inhibitors, are included. There is no estimate given for off-label usage or usage for reversal of over-anticoagulation, for which we do not have data.
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2.5 Rarer Bleeding Disorders
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Table 22 Patients with rarer types of bleeding disorders registered and treated April 2017 & March 2018
Total Males Females Any
Product Concen‐trate
Desmo‐pressin
Probable von Willebrand disease 228 58 170 14 1 13 6.1
Platelet‐type Pseudo von Willebrand Disease 34 15 19 2 2 0 5.9
F.V deficiency 218 85 133 3 2 0 1.4
F.VII deficiency 1,420 680 740 67 65 0 4.7
F.X deficiency 266 115 151 35 22 0 13.2
F.XI Deficiency 3,274 1,354 1,920 71 48 0 2.2
F.XIII Deficiency 71 40 31 59 59 0 83.1
Combined II+VII+IX+X Deficiency 3 1 2 0 0 0 0.0
Combined V+VIII Deficiency 27 12 15 11 11 1 40.7
Co‐inherited diagnoses 306 151 155 31 27 6 10.1
Prothrombin Deficiency 13 5 8 3 3 0 23.1
Afibrinogenemia 16 9 7 14 13 0 87.5
Dysfibrinogenemia 532 215 317 19 19 0 3.6
Hypofibrinogenemia 155 67 88 7 7 0 4.5
Hypodysfibrinogenemia 33 16 17 2 2 0 6.1
Fibrinogen Deficiency 16 8 8 1 1 0 6.3
Acquired Haemophilia A 525 274 251 95 91 1 18.1
Acquired Haemophilia B 1 1 0 0 0 0 0.0
Acquired von Willebrands 134 73 61 35 34 1 26.1
Acquired Prothrombin Deficiency 7 4 3 0 0 0 0.0
Acquired F.XIII Deficiency 1 0 1 0 0 0 0.0
Acquired F.V Deficiency 5 0 5 0 0 0 0.0
Acquired Deficiency (other) 11 8 3 1 0 1 9.1
Glanzmann's Thrombasthenia 141 63 78 50 46 4 35.5
Bernard Soulier 92 44 48 12 10 1 13.0
Other platelet defects 2,685 823 1,862 108 2 89 4.0
Miscellaneous 275 72 203 16 5 10 5.8
Unclassified bleeding disorder 588 81 507 37 4 31 6.3
Haemophilia A with Liver Transplant 10 10 0 0 0 0 0.0
Haemophilia B with Liver Transplant 2 2 0 0 0 0 0.0
Total 11,089 4,286 6,803 693 474 158 6.2
Treated with Coagulation Defect
Number of Patients in Register %
Treated
Table 22 This shows patients registered with rarer disorders and the proportion treated during the year. It is suspected that liver transplantation is under-reported.
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Table 23 Patients with selected rarer bleeding disorders registered and treated April 2017 – March 2018, by disease severity
In Reg Treated In Reg Treated In Reg Treated In Reg Treated
F.V deficiency 46 2 172 1 0 0 218 3
F.VII deficiency 130 26 1287 40 3 1 1420 67
F.X deficiency 41 28 225 7 0 0 266 35
F.XI Deficiency 245 28 3027 43 2 0 3274 71
Total 462 84 4,711 91 5 1 5,178 176
Coagulation Defect
Number of Patients (factor level IU/dl)
<5 ≥5 N/K Total
Table 23: It is acknowledged that these rarer disorders have no recognised classification of disease severity. However, the table above gives an idea of the range of registered levels.
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Table 24 New registrations of rarer bleeding disorders between April 2017 & March 2018 showing their coagulation defect and gender
Coagulation Defect Male Female Total
Platelet‐type Pseudo von Willebrand Disease 1 6 7
Probable von Willebrand disease 6 27 33
F.V deficiency 5 10 15
F.VII deficiency 77 94 171
F.X deficiency 8 12 20
F.XI Deficiency 114 187 301
F.XIII Deficiency 2 2 4
Combined V+VIII Deficiency 0 1 1
Co‐inherited diagnoses 13 9 22
Afibrinogenemia 1 1 2
Dysfibrinogenemia 27 21 48
Hypofibrinogenemia 12 14 26
Hypodysfibrinogenemia 3 2 5
Acquired Haemophilia A 62 41 103
Acquired F.V deficiency 0 1 1
Acquired Prothrombin Deficiency 0 1 1
Acquired von Willebrand disease 7 8 15
Acquired Deficiency (other) 2 2 4
Glanzmann's Thrombasthenia 6 4 10
Bernard Soulier 1 4 5
Other platelet defects 84 219 303
Miscellaneous 5 19 24
Unclassified bleeding disorder 20 105 125
Total 456 790 1,246
Table 24: This table shows new registrations during the year. As usual, this continues to show a consistent excess of female registrations for all autosomal disorders, presumably reflecting referral and diagnostic bias of women with menorrhagia.
Tab
le 2
5 C
once
ntra
tes
used
to tr
eat r
arer
ble
edin
g di
sord
ers
betw
een
Apr
il 20
17 &
Mar
ch 2
018
Pts
trea
ted
Units
Pts
trea
ted
Units
Pts
trea
ted
Units
Pts
trea
ted
Units
Pts
trea
ted
Units
COAGADEX
‐ ‐ ‐ ‐ 5 338,470
‐ ‐ ‐ ‐
FXI
‐ ‐ ‐ ‐ ‐ ‐ 35
147,733 ‐ ‐
Beriplex
‐ ‐ ‐ ‐ 13
716,500
‐ ‐ ‐ ‐
Fibrogammin P
‐ ‐ ‐ ‐ ‐ ‐ ‐ ‐ 58
868,750
FXIII
‐ ‐ ‐ ‐ ‐ ‐ 2 3,572 ‐ ‐
LFB Biomedicam
ents
Hemoleve
n ‐ ‐ ‐ ‐ ‐ ‐ 13
137,000 ‐ ‐
Novo
Seve
n (mg)
1 18
64
3,206 ‐ ‐ 2 124 ‐ ‐
Novo
Thirteen
‐ ‐ ‐ ‐ ‐ ‐ ‐ ‐ 1 32,500
Octap
las (units)
2 1,710 ‐ ‐ ‐ ‐ 16
1,309 ‐ ‐
Octap
lex
‐ ‐ ‐ ‐ 18
1,179,500
‐ ‐ ‐ ‐
Advate
1 39,000
1 1,250 ‐ ‐ ‐ ‐ ‐ ‐
FEIBA
1 64,000
‐ ‐ ‐ ‐ ‐ ‐ ‐ ‐
FVII
‐ ‐ 2 268,800 ‐ ‐ ‐ ‐ ‐ ‐
Shire
BPL
CSL Behring
Octap
harma
F.XIII De
ficiency
Novo
Nordisk
Man
ufacturer
Prod
uct
F.V de
ficiency
F.VII d
eficiency
F.X de
ficiency
F.XI Deficiency
Uni
ts in
IU u
nles
s ot
herw
ise
stat
ed
Tabl
e 25
: T
his
give
s a
brea
kdow
n of
pro
duct
use
dur
ing
2017
/18
for
UK
pat
ient
s w
ith r
arer
ble
edin
g di
sord
ers,
bro
ken
dow
n by
dia
gnos
is
and
supp
lier.
Page | 73
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
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2.6 Adverse Events
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Table 26 Adverse Events reported between April 2017 & March 2018
Adverse EventNumber of Patients
Number of Events
Allergy Event 8 8
Infection Event 1 1
Inhibitor Event 23 23
Intracranial Haemorrhage 6 6
Malignancy Event 18 18
Other Event 8 9
Poor Efficacy Event 0 0
Thrombotic Event 10 10
Total 74 75
See table 17 for breakdown of inhibitors by disease severity in haemophilia A, B and von Willebrand disease
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2.7 Morbidity and Mortality
Tab
le 2
7 C
ause
s of
dea
th in
pat
ient
s w
ith h
aem
ophi
lia A
and
B b
etw
een
Apr
il 20
17 &
Mar
ch 2
018
< 1
1 ‐ 5
>5 & <40
≥ 40
Unk
nown
Total
< 1
1 ‐ 5
>5 & <40
≥ 40
Unk
nown
Total
AIDS
00
00
00
01
00
01
ARDS
01
00
01
00
00
00
Carcinoma
24
71
115
00
10
01
Cerebral h
aemorrhage
10
30
04
00
00
00
COAD
00
10
01
00
00
00
Hae
morrhage (Misc)
20
00
02
00
00
00
Hepatocellular Carcinoma
00
10
01
00
00
00
Infection (Bacterial)
00
51
06
00
00
00
Ischae
mic Heart Disease
20
60
08
00
00
00
Pan
creatitis
00
01
01
00
00
00
Renal Failure
10
00
01
10
00
01
Ruptured Aorta (Peripheral
vascular disease)
00
00
00
00
10
01
Stroke
(Unkn
own)
01
00
01
00
00
00
Suicide
10
00
01
00
00
00
Unkn
own
35
244
036
11
40
06
Totals
1211
477
178
22
60
010
Haem
ophilia
AHa
emop
hilia
B
Cause of Dea
thSe
verity (factor V
III le
vel IU/dl)
Seve
rity (factor IX leve
l IU/dl)
Tabl
es 2
7 &
28:
T
hese
sho
w t
he c
ause
s of
dea
th a
mon
gst
patie
nts
with
hae
mop
hilia
A a
nd B
(in
clud
ing
carr
iers
), b
roke
n do
wn
by s
ever
ity
(Tab
le 2
7) a
nd f
or o
ther
ble
edin
g di
sord
ers
(Tab
le 2
8) d
urin
g 20
17/1
8.
At
pres
ent,
it ca
n be
asc
erta
ined
who
has
die
d fr
om t
he N
HS
spi
ne
but o
ur o
nly
sour
ce o
f cau
se o
f dea
th d
ata
is fr
om h
aem
ophi
lia c
entr
es th
emse
lves
. A
ll ca
uses
of d
eath
sho
uld
be r
epor
ted
to th
e da
taba
se,
whe
re th
is is
kno
wn.
Page | 77
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
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Table 28 Causes of death in other coagulation defects between April 2017 & March 2018
Coagulation Defect Cause of Death Total
F.V deficiency Unknown 2
Haemorrhage (Misc) 1
Unknown 9
F.X deficiency Unknown 1
Accident 1
Carcinoma 2
Infection (Bacterial) 1
Ischaemic Heart Disease 1
Ruptured Aorta (Peripheral vascular disease) 1
Unknown 26
Co‐inherited diagnoses Unknown 1
AIDS 1
Aortic stenosis 1
Carcinoma 2
Cerebral haemorrhage 1
COAD 1
Haemorrhage (misc) 2
Infection (Bacterial) 16
Ischaemic Heart Disease 7
Pancreatitis 1
Renal Failure 1
Senility/Alzheimer's disease 1
Stroke (thrombotic) 1
Unknown 55
Acquired F.V deficiency Unknown 1
Carcinoma 1
Unknown 6
Carcinoma 1
Infection (Bacterial) 1
Renal Failure 1
Unknown 1
Hypofibrinogenemia Unknown 2
Prothrombin Deficiency Unknown 1
Carcinoma 2
Senility/Alzheimer's disease 1
Unknown 13
Miscellaneous COAD 1
Unclassified bleeding disorder Unknown 5
AIDS 1
Carcinoma 4
Cerebral haemorrhage 1
COAD 1
Haemorrhage (Misc) 1
Hepatocellular Carcinoma 2
Infection (Bacterial) 2
Liver Failure 2
Stroke (Unknown) 1
Unknown 31
Total 219
Platelet defects
von Willebrand disease
Acquired von Willebrand Disease
F.XI Deficiency
F.VII deficiency
Acquired Haemophilia A
Dysfibrinogenemia
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Figure 19 Cumulative incidence chart of deaths from hepatocellular carcinoma or liver failure in UK patients with bleeding disorders 1969 - 2017
0
50
100
150
200
250
300
Cumulative Pa
tient Dea
ths
Year of death
HepatocellularCarcinoma
Liver Failure Total
YearHepatocellular Carcinoma
Liver Failure
Total YearHepatocellular Carcinoma
Liver Failure
Total
1969 0 2 2 1996 0 10 10
1970 0 2 2 1997 0 10 10
1972 0 2 2 1998 0 9 9
1973 0 1 1 1999 0 4 4
1974 0 1 1 2000 0 15 15
1975 0 1 1 2001 1 6 7
1979 0 2 2 2002 3 9 12
1980 0 1 1 2003 2 2 4
1983 0 2 2 2004 3 4 7
1984 0 3 3 2005 1 2 3
1985 0 4 4 2006 4 5 9
1986 0 7 7 2007 2 3 5
1987 0 5 5 2008 3 6 9
1988 1 2 3 2009 2 8 10
1989 0 5 5 2010 2 9 11
1990 0 4 4 2011 2 5 7
1991 0 9 9 2012 3 8 11
1992 0 9 9 2013 9 9 18
1993 0 15 15 2014 0 4 4
1994 0 13 13 2015 2 9 11
1995 0 7 7 2016 0 2 2
2017 0 2 2
Total 40 238 278
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Figure 19: This shows deaths directly attributable to liver disease. Bear in mind that most patients with bleeding disorders who die, do not die from liver disease.
Overall figures for deaths amongst bleeding disorders have been repeatedly misquoted in the media suggesting that all deaths are caused by HCV. This is not the case. The above table documents the number whose death certificate listed liver disease as the principal cause of death. Liver disease may have been a subsidiary contributory factor in other deaths but was not listed as the primary cause on the death certificate.
This appears to show some levelling-off of deaths from hepatocellular carcinoma (HCC) and from hepatocellular failure. This may be a reporting artefact in that we have not received death certification data from NHS Digital for two years, although we also collect reports of death directly from the haemophilia centres. However, as HCV is eradicated from a higher and higher proportion of patients, one would expect a reduction in the incidence of HCC, which declines dramatically after viral eradication, even in the presence of ongoing cirrhosis. There may be a delay before we see a reduction in deaths from hepatocellular failure, since some patients do have advanced cirrhosis with hepatocellular failure and not all are suitable for transplant or have a donor. However, successful viral eradication will result in complete recovery for patients with early cirrhosis or less advanced liver disease and they should not go on to develop advanced cirrhosis or die from complications of HCV.
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Table 29 Summary of patients ‘at risk’ of vCJD for public health purposes who received UK sourced plasma products as reported by centres
Implicated batches
Non‐implicated batches
Combined
Alive 674 2525 3199
Dead 136 692 828
Total 810 3217 4027
MM ‐ ‐ 5
MV ‐ ‐ 4
VV ‐ ‐ 1
Not known 810 3217
M 770 2640 3410
F 40 577 617
0‐19 0 6 6
20‐39 303 771 1074
40‐59 267 1025 1292
60‐79 100 608 708
80+ 4 113 117
Not known 0 2 2
Sex
Current age band of living
‘at risk’ patients
Summary table of ‘at risk’ bleeding disorder patients who received UK sourced plasma products
Current status of ‘at risk’
patients
Genotype
These data were last updated on 30/06/2018
Table 29: This report is sent to Public Health England on a bi-annual basis. No patients with bleeding disorders have ever developed vCJD.
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Figure 20 Total number of patients with haemophilia A, haemophilia B or von Willebrand disease treated by UK haemophilia centres
0
2
4
6
8
10
12Num
ber o
f Cen
tres
Number of treated patients
Figure 21 Total number of patients with severe haemophilia A and haemophilia B treated by UK haemophilia centres
0
2
4
6
8
10
12
14
16
18
20
Num
ber o
f Cen
tres
Number of treated patients
N.B: haemophilia A includes: Carrier of haemophilia A and females with FVIII deficiency Haemophilia B includes: Carrier of haemophilia B, females with FIX deficiency, FIX Leyden and FIX Leyden carriers
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Appendix 2: Participating Centres
Aberdeen Leicester
Abergavenny Lewisham
Bangor Lincoln
Barnstaple Liverpool (R. I.)
Belfast ‐ Adult's Liverpool Children's
Belfast ‐ Children's Manchester (Adults)
Birmingham (Queen Elizabeth) Manchester Children's
Birmingham Children's Newcastle upon Tyne
Bournemouth / Poole North Hampshire (Basingstoke)
Bradford North Staffordshire (Stoke on Trent)
Brighton Norwich
Bristol (Infirmary & Children's) Nottingham
Cambridge Oxford
Canterbury Peterborough
Cardiff Plymouth
Chichester Portsmouth
Coventry Royal Free
Derby Salisbury
Dundee Sheffield (Children's)
Edinburgh Sheffield (Royal Hallamshire)
Exeter Shrewsbury
Glasgow (R.H.S.C.) Southampton
Glasgow (R.I.) St George's Hospital, London
Great Ormond Street St Thomas' and Guy's Hospital
Hammersmith Hospital, London Swansea
Inverness Taunton / Yeovil
Ipswich The Royal London Hospital
Kettering Torquay
Kingston upon Hull (Hull) Truro
Lancaster Wolverhampton
Leeds York
Centre Name
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3. Haemtrack Annual Report 2017 Introduction
This report is reported by calendar year rather than by financial year since 10% of the data is reported on paper, after a delay.
Haemtrack is used by patients to report home therapy to their haemophilia centre and so its use is not limited to haemophilia A or B but includes other, rarer, bleeding disorders for which patients also use home therapy. Both haemophilia centres and patients vary in their reporting compliance with Haemtrack and so the quality of individual patient self-reported data varies and the proportion of patients using the system also varies from centre to centre. In general, data quality is improving and the proportion of patients using the system is increasing.
Our aim is that Haemtrack should become a routine part of home-therapy management and a valuable tool for the review and optimisation of home-therapy and for patient education. For that to happen, compliance will have to improve and be reinforced by Health Care Professionals (HCP’s) reviewing Haemtrack records with patients in clinic and checking the data for accuracy before downloading into HCIS, where it should be checked by HCPs prior to uploading into the National Haemophilia Database.
Haemtrack should also be used in multidisciplinary team meetings (MDTs). Many haemophilia centres already do this and in those centres recruitment and data quality are steadily improving. This requires a consistent investment in time by the centre staff which results in improving compliance with both home therapy and record keeping.
Some haemophilia centres appear not to have realised the full clinical utility of this reporting system and consequently return sub-optimal data, which may reflect some degree of non-engagement by both HCPs and their patients. It is important to demonstrate to the patient, by referring to Haemtrack data on screen in clinics, that collecting and reporting treatment data is useful for their clinical management, and that it’s collection is not just an empty bureaucratic exercise.
NHS funding has come under extreme pressure and NHS England, desiring responsible use of drugs and accountability, have made it clear that compliant use of Haemtrack will be a prerequisite for access to more expensive new treatments such as Hemlibra® and EHL-IX. NHS England require hard proof that these drugs are cost effective in normal use and that they improve outcome.
For that reason, it is necessary to be able to demonstrate that the use of resources is being closely monitored and the way in which these resources are used can be accounted for. Patient-reported data, such as Haemtrack, is an important element of this and so it is important that centres take steps to obtain more complete data from a higher proportion of their patients. This may require significant effort and may also have staffing implications at a centre level, which will have to be addressed but which could be funded from the CQUIN budget or as part of the forthcoming service review.
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Section 1: Patients’ Haemtrack Usage Analysis 1.1 Overall
Figure 1 presents an overview of severe and moderate patients with haemophilia A or haemophilia B using Haemtrack from 2008 to 2017. The blue columns give the numbers of patients that on Haemtrack and the lines show the proportion of NHD patients who use Haemtrack. This illustrates rapid growth in 2012, when recruitment was the subject of a CQUIN. Figure 1 also reveals that there has been a gradual rise in the rate of recruitment, especially in severe haemophilia A cohort.
Figure 1 Number of patients using Haemtrack and recruitment rate, 2008-2017
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1.2 Haemtrack usage analysis at centre level - patients with severe Haemophilia
Use of Haemtrack has increased at a rapid rate in recent years and most Comprehensive Care Centres (CCCs) use Haemtrack to some degree, though far fewer Haemophilia Centres (HCs). This may relate to staffing issues and perhaps a lower degree of engagement in HCs who may only have a few patients suitable for the system.
Figures 2 and 3 display the proportion of patients with severe haemophilia A/B using Haemtrack in each CCC (Figure 2) and HC (Figure 3). Recruitment is a little better in CCCs than in HCs.
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Figure 2 Comparison of recruitment to Haemtrack by centre for patients with severe haemophil ia A: Comprehensive Care Centres (CCCs) in 2017
Figure 3 Comparison of recruitment to Haemtrack by centre for patients with severe haemophil ia A: Haemophil ia Centres (HCs) in 2017
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Compliance with record keeping amongst patients using Haemtrack also varied considerably. For the purposes of this report, compliance refers to the patient’s annual product usage reported through Haemtrack as a proportion of the factor issued to the patient, as reported quarterly to the NHD. Good compliance has been arbitrarily defined as Haemtrack reporting of use of >75%.
Figure 4 and 5 exhibit the overall compliance by patients for CCCs and HCs respectively. The compliance value closer to 100 indicates better usage compliance. The figures show the mean (diamond), median (vertical line), interquartile range (bar) and range (whiskers) compliance.
The median compliance in patients with severe haemophilia A from CCCs and HCs in 2017 are 89% and 90% respectively. This shows that, although fewer HCs use Haemtrack than CCCs, the quality of reporting is similar. In 2016, the median values of compliance for CCCs and HCs are 78% and 80% respectively.
Compliance has improved considerably in recent years, both in CCCs and HCs, and is generally quite good.
Figure 4 Overall compliance in patients with severe haemophil ia A, by Comprehensive Care Centre
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
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Figure 5 Overall compliance in patients with severe haemophil ia A, by Haemophil ia Centre
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
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Section 2: Patients’ Reporting Analysis
2.1 Patients’ Reporting Medium
Figure 6 shows the proportion of Haemtrack users using different reporting methods between 2011 and 2017. This shows an initial rapid uptake of the use of the web application at the expense of paper reporting. Subsequently, when the iPhone and then the Android app were introduced, they rapidly gained popularity at the expense of the web application. Oddly, the use of paper has remained stable over the past several years. This is curious given that electronic data can be very quickly quality-checked and rapidly imported into the haemophilia Centre Information System (HCIS) whereas paper records need to be laboriously keyed in by centre personnel. Most centres have a small proportion of patients using paper, but some centres still have most of their patients reporting on paper even though this creates more work for centre staff. The number of patients who are statistical outliers for compliance and use a paper reporting system suggests that some of these records had been manually entered by centres without checking or reconciliation. More recently, there seems to be a considerable increased in checking at centre level since there are far fewer obvious errors.
Figure 6 Change in the use of different Haemtrack Reporting Media: 2011- 2017
This is further analysed in Figure 7, which breaks down the interval between treatment and reporting by the reporting method used (smartphone apps, web and paper). Use of phone apps is associated with the most rapid reporting, with almost 40% of data being recorded on the day of treatment and a further 30% within a week. In contrast, only 18% of treatments were
UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018
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reported the same day and a further 25% within a week using web. Most data submitted on paper was reported after an interval of up to 3 months, either by post or at the next review clinic. Data reported by phone app was returned after a median of only 2 days, whereas paper-recorded data was reported after a median of 54 days with the web being intermediate. There is no difference in the median age of patients using phone app and web, while the patients using paper are older than those two groups, the median age being 24, 24 and 31 years for phone app, web and paper reporters, respectively.
We are actively promoting the use of the iPhone and Android apps in preference to other methods of reporting because we believe that the data are not only available to centres more quickly but are likely to be more accurate.
Haemtrack 2 has been launched during the course of the year and patients are slowly changing to this. Being completely web-based, it may be used on any smartphone and will synch automatically but is dependent on having a Wi-Fi connection. This version is also easier to use.
We will have extended the use of Haemtrack to inpatient use (data entered by centre staff) so that it will provide a complete treatment record.
Figure 7 Haemtrack Reporting Delay by Reporting Medium 2017
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Figure 8 Reporting compliance by reporting medium, ranked by median compliance 2017 (CCC’s) in patients with severe haemophil ia A
Figure 8 exhibits box and whisker plots of compliance broken down by reporting medium used for patients with severe haemophilia A from CCCs. Boxes show the 25th to 75th percentiles; whiskers the arithmetic range. The vertical black line shows the median and the diamond shows the mean.
It is clear that electronic reporting methods returned better compliance than paper form. In 2017, the number of patients using only phone apps is 564 and those using web only is 342. Eighty-two patients continue to “prefer” paper. The number of patients choosing to use two reporting mediums was 216 and 9 patients used three mediums. All combinations of electronic reporting showed similar levels of compliance. This may be selection bias. Those using phone apps were, by and large, using web before. The patients using more than one medium to report their treatments may have changed their reporting medium in the year.
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4. Data Management Working Party
Membership
Chair: Professor Peter Collins
Commissioner representative: Will Horsley Director(s) of the National Haemophilia Database: Professor Charles Hay Data Managers’ Forum representative: Lynne Dewhurst Haemophilia Nurses Association representative: Emma Franklin Haemophilia Physiotherapists Group representative: David Stephenson Haemophilia Society representative: Liz Carroll MDSAS representative: Dr Rob Hollingsworth Patient representative: Barry Flynn Representatives of Northern Ireland, Scotland and Wales: Northern Ireland Dr Gary Benson Scotland Dr Elizabeth Chalmers Wales Professor Peter Collins UKHCDO Working Party Chairs: Co-morbidities Working Party Dr Rhona Maclean Genetics Working Party Dr Keith Gomez Inhibitor Working Party Dr Dan Hart Musculoskeletal Working Party Dr Pratima Chowdary Paediatric Working Party Dr Elizabeth Chalmers Peer Review Working Party Dr John Hanley Von Willebrand Working Party Prof Mike Laffan UKHCDO Executive Committee: Chair Dr Ri Liesner Secretary Dr Kate Talks (Other execs listed above) Members of the NHD as nominated by the Director(s) of the National Haemophilia Database: Working Party Secretary Lynne Dewhurst Bruce Cowen Ben Palmer Dr Hua Xiang Meetings
The UKHCDO Data Management Working Party (DMWP) met on 11th May 2018 (Manchester) and 28th Sept 2018 (London). The terms of reference for the Working Party are available on the UKHCDO website.
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The DMWP oversees all aspects of data collection and analysis of patients with inherited bleeding disorders undertaken by the National Haemophilia Database (NHD). The DMWP and NHD are jointly responsible for the accuracy and completeness of the data collected. The DMWP has delegated most of the responsibility for assessing and overseeing requests for analysis of NHD data to the Data Analysis Group (DAG) which is a subcommittee of the DMWP.
The DMWP regularly reviews the information that is collected on patients and revises this as necessary. Any member of UKHCDO can suggest changes to the data that are collected and these will be considered by the DMWP. At present the way that platelet disorders are recorded is being updated.
All members of UKHCDO are encouraged to suggest data analyses to the DMWP and DAG, this can be done by individual members or through UKHCDO Working Parties.
Examples of ongoing UKHCDO projects supported by NHD are:
The Acquired Haemophilia A registry Immune Tolerance Induction registry Enhanced half-life factor VIII and IX registry Mortality in severe haemophilia
The DMWP and NHD are ensuring that the Infected Blood Inquiry has full access to the information held by the NHD along with any help in the interpretation of that data that is required by the Inquiry.
Haemtrack
The Haemtrack system continues to expand with more patients registered and more treatments recorded. Commissioners for England and the devolved countries of the UK encourage the use of Haemtrack as a means of capturing individual patient events and treatment. This has allowed important information about the impact of enhanced half-life factor VIII and IX to be collated. The introduction of Emicizumab will be closely observed with particular focus on any thrombotic events.
Haemtrack Video Consultation – Haemtrack has the ability for clinicians to hold patient video consultations within the Haemtrack system. This can be accessed through “clive.mdsas.com”
IT update
Centres can now record on HCIS whether a patient is taking prophylaxis and what the prescribed regimen is.
It is planned that the database will be re-written over the next few years to ensure ongoing functionality. This will be a major undertaking jointly performed by NHD and MDSAS.
NHD aims to link with the WAPPS-Hemo (www.WAPPS-HEMO.org) population pharmacokinetics programme run by McMaster University. This link will allow centres to input 2-3 factor VIII or factor IX levels and receive an interactive read out that allows levels to be predicted at any time after an infusion. In addition, the effect of potential prophylactic regimens can be explored with patients to better optimise treatment. The system has the advantage that all concentrates, including enhanced half-life factor VIII and IX, can be used.
UKHCDO would like to thank many individuals involved in the work of the NHD. Professor Hay is the clinical Director of NHD and oversees its function on a day to day basis on behalf of UKHCDO.
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The following people work for the National Haemophilia Database and have been invaluable in their very high-quality work collecting and analysing the data on our behalf.
Katie Allen Helen Brown Bruce Cowen Lynne Dewhurst Rachel Lockwood Ben Palmer Sarah Rooney Tom Sharpe Hua Xiang
We also thank Rob Hollingsworth and MDSAS for their continued support and maintenance of our national information systems.
We also wish to acknowledge all the important work done at the centre level and for the support of all the patients for supporting this important work.
Prof Peter Collins, Chair UKHCDO Data Management Working Party
Prof Charles RM Hay, Director NHD
September 2018
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5. Data Analysis Group
Membership
Co-Chair (Chair of Data Management Working Party) Professor Peter Collins
Co-Chair (Director of NHD) Professor Charles Hay
User representatives: Dr Ryan Cheal Paul Sartain
UKHCDO members: Dr Elizabeth Chalmers Dr Pratima Chowdary Dr Dan Hart Dr Ri Liesner
Haemophilia Nurses and Physiotherapy representatives: Simon Fletcher David Stephenson
National Haemophilia Database: Bruce Cowen Lynne Dewhurst Ben Palmer Dr Martin Scott (observer) Dr Hua Xiang
Meetings
The Data Analysis Group (DAG) is a subgroup of the Data Management Working Party. Its role is to assess and prioritise applications to analyse data held by NHD, including Haemtrack and joint score data. Applications are assessed based on data governance considerations, scientific merit and available resources. The group meets once a month by teleconference which last on average 60-90 mins. The DAG has met every month since April 2017. The terms of reference of the DAG are available on the UKHCDO website.
Requests for analyses are submitted on a standardised form. This form is available from NHD.
The DAG reviews and discusses all applications. It provides feedback to the applicant and works with them to refine the proposal, if necessary. The contributions from the user representatives have been particularly useful in assessing the applications.
The data analyses that are generated from the requests are reviewed and commented on by the group and may be further revised, if necessary, before release.
The DAG is developing an investigator-led proposal to Roche/Chugai to analyse data held on the NHD relating to the introduction of Emicizumab.
Requests for data analyses have been submitted by individual members of UKHCDO, UKHCDO working parties, NHS England, NHS Wales and pharmaceutical companies.
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All members of UKHCDO and UKHCDO working parties are encouraged to suggest analyses and are invited to collaborate with the DAG on these projects. The DAG is open to new members from UKHCDO and anyone interested should contact Charlie Hay and Peter Collins.
Prof Peter Collins, Chair UKHCDO Data Management Working Party
Prof Charles RM Hay, Director NHD
September 2018
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6. Co-Morbidities Working Party
Membership
Chair Rhona Maclean
UKHCDO representatives: Gary Benson, Belfast Bella Madan Guys and St Thomas’ Mike Makris, Sheffield Gillian Evans, Canterbury Susie Shapiro, Oxford Sarah Mangles, Basingstoke Gerry Dolan, Guys and St Thomas Jason Coppell, Exeter
Haemophilia Nurses Association Representative: Cathy Harrison, Sheffield
Haemophilia Physiotherapist’s Group Representative: Fionnuala Sayers, Belfast
The terms of reference for this working party were agreed in September 2018.
Lines of Responsibility
The Co-Morbidities Working Party (CMWP) is responsible to the UKHCDO Executive and Advisory Committees.
The UKHCDO Executive and Advisory Committees approve the terms of reference and approve the remit of the CMWP
The chair of the CMWP – or representative- will participate in the UKHCDO Data Management Working Party (DMWP).
Remit
To consider comorbidity issues in patients with bleeding disorders within the UK and review any unmet need with respect to data collection, guidelines and patient related information / material.
To develop a Work Plan for the CMWP.
To advise the DMWP as to what data the NHD should collect regarding comorbidities in patients with haemophilia and bleeding disorders.
Any publications arising from the CMWP should be approved by the UKHCDO Executive in line with the UKHCDO publication policy.
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7. Genetics Working Party
Membership
Keith Gomez Chair Nicola Curry Gerry Dolan Steve Keeney Representing Genetics Laboratory Network Mike Laffan Megan Sutherland Representing Genetics Laboratory Network
Remit
1. Continue role as oversight committee for issues related to genetics in haemophilia 2. Annual guideline review 3. Support ThromboGenomics programme and enrolment of patients in NIHR UK
Biobanking initiative 4. Support genetic analysis of all patients with inherited bleeding disorders and for results
to be recorded on NHD 5. Provide oversight of gene therapy trials for haemophilia in the UK
Meetings and work streams
The working party met by teleconference in October 2017 and September 2018.
The working party has produced a new good practice paper entitled Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. This has been submitted for publication.
The provision of genetic testing services in England has been revised by NHS England with a consolidation of services into four hubs. We are currently in the transition period and over the next year, the testing of samples will be transferred to the hubs. There should not be any break in service provision, but for many members the testing laboratory will change. On behalf of UKHCDO the Genetics Working Party responded to the NHS England stakeholder consultation regarding potential issues regarding the quality of genetic reporting. We have been used to a service tailored to the needs of UK haemophilia clinicians and the working party will monitor the service to assess how this is maintained.
The ThromboGenomics platform continues to be the main platform providing testing for genes in rare bleeding and platelet disorders. The long-term provision of this service is unclear following the NHS England service reconfiguration, but the current plan is for it to continue perhaps with a testing fee. Genomics England 100K project is due to close later this year and it is not clear whether a similar testing platform will be introduced to replace it.
There are now 11 centres enrolling patients into the NIHR rare diseases project. As of June 2018, 869 patients had been enrolled including 340 from Liverpool and 236 from Oxford.
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A proposal for revising the registration of heritable platelet disorders has been submitted to the Data Management Working Party. This should allow capture of the genetic variants and other phenotypic features.
The table below shows the capture of genetic diagnosis for haemophilia A and B as of end of April 2018. There is regional variability in submission of data with some examples of incomplete submission. This is partly due to staffing issues in laboratories and will be monitored by the Genetics Laboratory Network.
Number of patients with a genetic diagnosis by region (based on patient's postcode and not registered centre)
Patients registered with the NHD 2017/18 Haemophilia A includes females with VIII deficiency & haemophilia A carriers Haemophilia B includes females with IX deficiency, haemophilia B carriers, FIX Leyden & FIX Leyden carriers
Dr K Gomez, Chair, Genetics Working Party
September 2018
< 1 1 & 5 > 5 40+ N/K
East Midlands 72 (41.9%) 11 (16.7%) 65 (20.8%) 10 (7.4%) 1 (10.0%)
East of England 28 (19.7%) 7 (8.0%) 39 (9.8%) 4 (2.7%) 0 (0.0%)
London 95 (27.5%) 22 (29.3%) 81 (19.2%) 9 (5.9%) 0 (0.0%)
North East 12 (17.4%) 8 (21.1%) 36 (29.3%) 20 (16.8%) 0 (0.0%)
North West 55 (26.8%) 28 (31.5%) 92 (25.1%) 23 (16.7%) 1 (20.0%)
Northern Ireland 43 (58.9%) 18 (60.0%) 66 (45.2%) 0 (0.0%) 0 (0.0%)
Scotland East 7 (8.4%) 4 (11.1%) 17 (10.0%) 0 (0.0%) 0 (0.0%)
Scotland West 2 (3.0%) 2 (6.3%) 3 (2.3%) 3 (2.5%) 0 (0.0%)
South East 99 (31.0%) 29 (36.7%) 82 (14.3%) 20 (11.2%) 0 (0.0%)
South West 33 (23.1%) 3 (4.4%) 19 (5.7%) 5 (7.7%) 0 (0.0%)
Wales 32 (39.0%) 9 (26.5%) 34 (18.7%) 4 (9.3%) 0 (0.0%)
West Midlands 37 (21.5%) 3 (5.1%) 15 (6.1%) 1 (1.0%) 0 (0.0%)
Yorkshire and the Humber 18 (12.2%) 4 (3.4%) 20 (5.5%) 8 (6.3%) 0 (0.0%)
Total 533 (26.4%) 148 (18.3%) 569 (15.1%) 107 (7.3%) 2 (2.8%)
East Midlands 7 (23.3%) 3 (14.3%) 4 (8.2%) 0 (0.0%) 0 (0.0%)
East of England 1 (2.6%) 2 (7.1%) 1 (1.2%) 0 (0.0%) 0 (0.0%)
London 4 (6.5%) 4 (7.1%) 8 (6.7%) 1 (2.2%) 0 (0.0%)
North East 2 (16.7%) 1 (9.1%) 1 (3.3%) 1 (3.6%) 0 (0.0%)
North West 8 (22.9%) 13 (35.1%) 14 (21.9%) 10 (21.7%) 0 (0.0%)
Northern Ireland 3 (33.3%) 1 (25.0%) 4 (23.5%) 0 (0.0%) 0 (0.0%)
Scotland East 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Scotland West 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
South East 7 (11.5%) 8 (14.3%) 11 (10.4%) 3 (9.4%) 0 (0.0%)
South West 1 (5.6%) 2 (11.1%) 6 (9.2%) 0 (0.0%) 0 (0.0%)
Wales 3 (27.3%) 13 (56.5%) 9 (27.3%) 0 (0.0%) 0 (0.0%)
West Midlands 5 (16.1%) 6 (35.3%) 2 (3.0%) 0 (0.0%) 0 (0.0%)
Yorkshire and the Humber 2 (7.7%) 0 (0.0%) 3 (6.3%) 3 (13.0%) 0 (0.0%)
Total 43 (12.0%) 53 (15.7%) 63 (8.2%) 18 (5.8%) 0 (0.0%)
Haemophilia B
Factor VIII / IX level (iu/dl)
Patients with a genetic diagnosis (% of registered patients)
Haemophilia A
Diagnosis Region
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8. Genetic Laboratory Network Background
The UKHCDO GLN was formed in 2002, arising out of the UKHCDO Genetic Working Party (UKHCDO GWP), with the aim of improving collaboration between laboratories and of ensuring quality and equity of service across the U.K. The network currently comprises 13 laboratories, 12 across the UK plus Dublin, involved in the molecular genetic analysis of haemophilia and related inherited bleeding disorders (many of the laboratories are also involved in other areas as well).
Representatives of the Network attend meetings of the UK Genetic Testing Network (UKGTN) and the UKHCDO GWP.
Meetings
The UKHCDO GLN holds bi-annual meetings and met on 21 November 2017 in London and 17 May 2018 in Cambridge. The next meeting is scheduled for November 2018 in Nottingham.
Chair & Secretary
Megan Sutherland and Catriona Keenan continue in their roles as Chair and Secretary, respectively.
Current activities
1. NHS England genetic laboratory re-designation exercise. During the current year the Genomics Laboratory Hub tendering process has been conducted by NHS England and a test directory has been produced which specifies services required to be delivered under the new service model in England, including bleeding disorders. Four entities have been selected to deliver this new service model and planning/implementation is underway. This represents a major change in bleeding disorder service configuration within England.
2. Laboratory Audit – ISO 15189: Laboratories in the Network are accredited by, or undergoing inspection for accreditation by, the United Kingdom Accreditation Service. Laboratories are required to adhere to ISO 15189 quality standards. The GLN continues to share examples of good practice, practical advice and knowledge as the inspection process is applied to member laboratories. The Network has implemented an informal sample exchange scheme between members of the GLN for disorders that are not provided for by UK NEQAS. The majority of laboratories have now successfully undergone the UKAS inspection process with the surveillance visit process now underway.
3. National Haemophilia Database (NHD) Genetics Portal: The NHD Genetics Portal allows members of the GLN to upload genetic variant data for patients they have investigated into the patient’s record on the NHD. The Genetics Portal is used by members of the GLN to see if a variant they have found has been reported by other centres, thereby providing evidence for pathogenicity calculations of genetic variation. During these searches the patient details are not shown. Members are also able to
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search for patients to confirm which centre they are registered at, and if a genetic variant has been reported prior to contact for release of relevant details if appropriate (no further information regarding the variant is made available).
4. Bleeding Disorder Genetic Analysis Best Practice Guidelines: The VWD genetic analysis guideline will be reviewed in accordance with the genetic test directory recently produced by NHS England and associated changes in service re-alignment (see item 1). Recent advances in the classification of genetic variation will also be considered and implemented in the guideline. The BPGs for Haemophilia A and Haemophilia B will also require review along similar lines once the new format has been created for the VWD guidelines.
5. Genetics of Heritable Bleeding Disorders NEQAS scheme: The Genetics of Heritable Bleeding Disorders EQA scheme, run by UK NEQAS in Sheffield, continues with bi-annual distributions. The results for each round of the scheme are reviewed and discussed at the following network meeting and any relevant comments fed back to the steering group. The scheme currently includes F8, F9 and VWF gene analysis. The GLN have discussed the need for further disorders to be included in the scope of the EQA scheme, in line with the published genetic test directory.
6. Participation in other groups: Representatives of the Network input to the UKHCDO GWP.
7. General: The GLN has discussed the application of next generation sequencing (NGS) approaches and traditional Sanger sequencing methods. GLN members who are currently using NGS analyse panels of genes and filter results according to the clinical indication. With the recent publication of the genetic test directory, analytical approaches to the investigation of heritable bleeding disorders will include both Sanger sequencing and NGS.
Megan Sutherland, Chair, UKHCDO Genetic Laboratory Network
October 2018
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9. Inhibitor Working Party
Membership
Dr Dan Hart Chair Dr Kate Talks Secretary Dr Elizabeth Chalmers Prof Peter Collins Dr Georgina Hall Prof Charlie Hay Dr Ri Liesner Prof Mike Makris Ben Palmer Dr Charles Percy Dr Anne Riddell
The Inhibitor Working Party (IWP) has been reconstituted and welcomed new membership. We have met twice face to face, a third time via a comprehensive teleconference call and multiple ad hoc communications to address the important issues emerging in this rapidly changing field.
IWP members led or contributed to clinical policy development for both recombinant porcine FVIII (susoctocog alpha, Obizur®, Shire) and biphenotypic FVIII-mimic antibody (Emicizumab, Hemlibra®, Roche). These have both now been NHS England approved for acquired haemophilia A (AHA) and congenital haemophilia A with inhibitors respectively and also adopted in devolved nations. Our laboratory survey and subsequent updates for the availability of the product specific assays identified the initial variation in availability of assays between centres, but importantly provided a document for centres’ labs to identify which neighbouring laboratories could perform these urgently if needed. Our laboratory specific email cascade has facilitated direct communication between NHD and lab chiefs and between labs in this key time of rapid change.
Obizur use in AHA has been included in the continuing national prospective data collection in AHA. This prospective data collection has entered its 3rd year and collected data on treatment and 12 months outcomes for over 300 AHA patients.
The launch of the early access scheme for Emicizumab in January 2018 required rapid generation of national guidance to treat bleeds in the presence of Emicizumab. These guidelines have been openly accessible via the Haemophilia journal since early in the year and remain a key reference document for treaters internationally. Our ongoing prospective collection of ITI outcome data is now integrating Emicizumab use as we continue to understand how to position this molecule in routine clinical care. Future NHD data will be crucial to inform this ongoing debate about the importance of long-term tolerance to FVIII. IWP members have had multiple discussions with various stakeholders to safeguard control and oversight of emerging data, whilst looking to find ways of working productively with other registries, either as product specific registries (e.g. Emicizumab) or in the European Medicines Agency future registries initiative.
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IWP and NHD team members have endeavoured to ensure clarification and rapid communication to the membership of any product specific adverse events and intend to launch an NHD, Emicizumab-specific prospective data collection (analogous to the AHA system) at the annual general meeting.
The past year has seen unprecedented change in the field of inhibitor therapeutics, laboratory monitoring and treatment algorithms. I am very grateful to the entire IWP membership who have all contributed to a much more fluid and demanding need than ever before to respond to events as they have emerged. Also, on behalf of the IWP membership, we would like to express our gratitude to all centres for their ongoing data returning for the multiple initiatives.
Dr D Hart Chair, Inhibitor Working Party
October 2018
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10. Laboratory Working Party
Agreed Process and Membership
Applications from UKHCDO members were invited by e mail and reviewed by UKHCDO exec. Membership to be reviewed on a 3-yearly basis
Group must compose of clinicians who treat haemophilia and Biomedical and Clinical Scientists who are involved in laboratory testing of patients with haemophilia
TTP and thrombophilia would not be covered in this working group – the specific focus is laboratory aspects of bleeding disorders, liaising with other working parties (e.g. inhibitor, VWD and rare bleeding disorders) when relevant
It was considered appropriate to have a maximum of 10 members
In addition, there will be a representative from NEQAS and NIBCS
Minutes are sent to the UKHCDO secretary
Meeting frequency to be determined by projects. At least once a year face to face
First meeting Monday 19th March 2018
Co-chairs
Dr Vincent Jenkins Laboratory Lead, Haemostasis and Thrombosis, University of Wales College of Medicine
Dr Will Lester Consultant Haematologist, Queen Elizabeth Hospital Birmingham
Working Party members and co-opted representatives from NEQAS and NIBSC:
Dr Steve Austin Consultant Haematologist, St George's Hospital London Dr Annette Bowyer Haemophilia Assays Section Lead, Royal Hallamshire Hospital
Sheffield Clive Burgess Haematology Laboratory Manager, Great Ormond Street Hospital for
Children London Dr Pratima Chowdary Consultant Haematologist, Royal Free Hospital London Dr Elaine Gray Principal Scientist representing National Institute for Biological
Standards and Control Dr Steve Kitchen Clinical Scientist representing NEQAS, Royal Hallamshire Hospital
Sheffield Paul Murphy Health Care Scientist, Royal Victoria Infirmary Newcastle Sean Platton Principal Biomedical Scientist , The Royal London Hospital Ms Anne Riddell Haemophilia Laboratory Manager, Royal Free Hospital London
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Remit
UKHCDO Lab Working Party Remit.
Current work streams
UKHCDO Guideline for laboratory monitoring of factor replacement therapy for patients with haemophilia A and B (chair EG) – Final draft Nov 18
UKHCDO Guidelines for laboratory measurements in haemophilia patients with inhibitors (chair VJ) – final draft Nov 18
Active list of specialist coagulation laboratories and test repertoires (chair AR)
Dr Vincent Jenkins & Dr Will Lester Co-Chairs, Laboratory Working Party
October 2018
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11. Musculoskeletal Working Party
Membership
Dr Pratima Chowdary Chair Dr Desmond Creagh Dr John Hanley Dr Angela McKernan Mr Peter Briggs Prof Simon Frostick Mr Nicholas Goddard Mr Paul McLaughlin Mr Stephen Classey Mrs Anna Wells Mrs Angela Westoby
Meetings
The Musculoskeletal Working Party (MSK) met once this year.
Activities/Plans
MSK working party this year has met once in person and by Teleconference on another occasion. Has had change in the Chair in the last year. Of the two guidelines the working party has agreed to author it was decided to prioritise the guideline related to standards of musculoskeletal care. As part of the work, the first round of Delphi consensus has been conducted and the second round will be completed later this year. Additional members have been invited to contribute to the first round of consensus. In addition, information on joint arthroplasty and synovectomy for patients are being reviewed.
Dr P Chowdary Chair, Musculoskeletal Working Party
October 2018
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12. Paediatric Working Party
Membership
Dr Elizabeth Chalmers Chair, Glasgow Dr Jeanette Payne Secretary, Sheffield Dr Jayanthi Alamelu London (Evelina) Dr Neha Bhatnagar Oxford Dr Tina Biss Newcastle Dr Mary Mathias London (GOSH) Dr Jayashree Motwani Birmingham Dr Mike Richards Leeds Dr Oliver Tunstall Bristol
The working party membership was renewed in October 2017.
Meetings
Two per annum with additional telecoms as required.
Last meeting: September 2018.
Summary of activities.
1. ITI Outcome data
• Retrospective follow up of Immune tolerance therapy in the UK (2003-2015)
Retrospective outcome data on the results of immune tolerance therapy in the UK (2003-2015 inclusive) has been collected from 8 UK CCCs treating children with inhibitors. Results of this analysis have been presented at the AGM previously & a manuscript is currently in preparation.
• Management & outcome of Immune tolerance using a standardised regimen (with inhibitor WP) - ongoing data collection in collaboration with IWP
A standard ITI protocol based on the current UKHCDO Guideline was agreed and commissioned previously. New inhibitors are reported to the NHD and prospective data collection on ITI outcomes has now been ongoing for almost 2 years. An update of the data collected so far will be presented at the AGM.
2. Intracranial haemorrhage in inherited bleeding disorders
Retrospective data collection (2003-2015) on cases of ICH occurring in children <16yrs of age in the UK has been completed and has been published in the journal Haemophilia. The data highlight the continuing risk of this complication in very young children with severe bleeding disorders. Prospectively data collection on ICH in both children and adults has been added to the NHD adverse events reporting scheme.
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The WP is also in the process of setting up a PUP registry via the NHD which will collect data on early exposure to FVIII and FIX in children with severe haemophilia. Data is also being collated in relation to the following areas:
• Inhibitors in Haemophilia B • Outcomes in moderate Haemophilia • Bleeding and treatment in children with rare coagulation disorders
The PWP also intends to pilot a national advisory group which will aim to act as a forum for advice on the management of children with inherited bleeding disorders. Further information on this will be circulated shortly.
Dr Elizabeth Chalmers Chair, Paediatric Working Party
October 2018
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13. Von Willebrand Working Party
Membership
Prof Mike Laffan Chair Dr Keith Gomez Dr Anne Goodeve Vince Jenkins Dr Will Lester Dr Carolyn Millar Dr Susie Shapiro Dr Henry Watson Dr Thynn Yee
The VWD working party was reformed in 2017 and the above membership agreed. The working party has not met since the last AGM.
Following the revised guidelines diagnostic categories and registration criteria there remains some work to complete on the revised registration form. This is ongoing with NHD.
A successful application was made to the Data Analysis Group for release of data which will allow the ‘Impact of revised classification on VWD registration in the UK’ to be assessed.
The 2014 guidelines will be reviewed in light of forthcoming ASH guidelines on diagnosis and management of VWD but do not require rewriting at present.
Prof Mike Laffan, Chair, Von Willebrand Working Party
October 2018
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14. Peer Review Working Party
Membership
Dr John Hanley Chair Dr Julia Anderson UKHCDO Member Dr Tina Biss UKHCDO Member Dr Gillian Evans UKHCDO Member Dr Lishel Horn UKHCDO Member Dr Ri Liesner UKHCDO Member Dr Rhona MacLean UKHCDO Member Dr Tim Nokes UKHCDO Member Anna Wells Lead Physio HCPA Sarah Bowman Social Worker Cathy Harrison Chair HNA Liz Carroll CEO Haemophilia Society Graham Knight Patient Representative Dr Kate Khair Past Chair HNA Dr Anne Yardumian Peer Review Programme Clinical Lead Rachael Blackburn Assistant Director WMQRS
As discussed and endorsed at the 2017 AGM, the Peer Review working party has continued a collaborative approach between the UKHCDO and the West Midlands Quality Review Service (WMQRS). Over the last 12 months the Working Party has met on several occasions.
The early part of the year focussed on finalising the Quality Standards for the care of Inherited and Acquired Bleeding Disorders. These were finalised and widely circulated.
WMQRS have coordinated the training for members of Peer review teams. 63 people have completed training and a further 36 are signed up for training.
The UK Peer Review programme will commence in November 2018. This will include visits to all Comprehensive Centres and several Haemophilia Centres. There will be 35 visits in total. Dates have been confirmed for 22 visits and 13 still to be confirmed.
The aim is to complete the programme of Peer Review visits over a 12-month period with the production of a summary report for the 2019 UKHCDO AGM. There will also be a Best practice sharing event in late 2019.
Dr John Hanley, Chair, Peer Review Working Party
October 2018
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15. Gynaecology Task Force
Membership
Dr Nikki Curry, Consultant Haematologist, Oxford Chair of writing committee
Dr Rezan Abdul-Kadir, Consultant Obstetrician and Gynaecologist, Royal Free Dr Louise Bowles, Consultant Haematologist, Royal London Professor Justin Clark, Consultant Obstetrician and Gynaecologist, Birmingham Dr Gill Lowe, Consultant Haematologist, Birmingham Dr Jason Mainwaring, Consultant Haematologist, Bournemouth Dr Sarah Mangles, Consultant Haematologist, Basingstoke Dr Bethan Myers, Consultant Haematologist, Leicester
The task force has met several times and have agreed the guideline structure and are awaiting the completion of the literature search to enable us to start writing the guideline. It will be a guideline that mirrors the UKHCDO obstetric guideline.
Dr Nikki Curry Chair, Gynaecology Task Force writing committee
October 2018
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16. Prophylaxis Task Force
Membership
Dr Rachel Rayment (adult) Co-Chair Dr Tina Biss (paediatric) Co-Chair Dr Steve Austin Dr Elizabeth Chalmers Kate Forsyth Dr Richard Gooding Dr Anne Kelly Dr Susie Shapiro Dr Kate Talks Dr Oliver Tunstall
The prophylaxis task force has met once in July 2017.
Remit of the group
This task force is in the process of revising and updating the UKHCDO/BSH guideline on the use of prophylactic factor concentrate in children and adults with haemophilia that was published in 2010.
The writing group are evaluating newer approaches to prophylaxis including the use of pharmacokinetic modelling, extended half-life products and novel molecules. The updated guidance will extend beyond severe haemophilia A to include guidance for individuals with non-severe haemophilia and haemophilia B. There will be a greater emphasis on prophylaxis use during adulthood including in adults with co-morbidities.
A literature search has been completed and the group aim to produce a first draft of the guideline by October 2018.
Dr Tina Biss, Co-Chair, Prophylaxis Task Force
September 2018
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17. Haemophilia Nurses’ Association
Membership
Cathy Harrison Chair Simon Fletcher Vice-Chair Shaun Emmitt Secretary Clare Forrester Sarah Johns April Jones Jenna Stanley Anne Wareing Dr Kate Khair (stepped down May 2018)
The Haemophilia Nurses Association (HNA) represents specialist nurses who care for people with bleeding disorders in the UK either through direct clinical practice or research. The last year has been exhilarating, and dominated by the WFH 2018 congress, held in May. HNA members participated in the treatment room and enjoyed meeting and treating people living with bleeding disorders from across the world and found collaborating with each other and with multidisciplinary peers a very rewarding experience.
As a consequence of WFH taking place in Glasgow, we chose not to run our annual conference in 2018, but instead convened a short AGM in the treatment room after the nurses’ day of the congress. We plan to hold a series of smaller, regional meetings throughout the autumn, giving us the opportunity to review topics presented at WFH, and to reassess the haemophilia nurse competency framework, which needs to be updated given the changing treatment landscape. The meetings will also focus on offering nurses peer review training. The new peer review process is due to start this Autumn/Winter and represents a vast change from the previous audit process. The review paper has been supported and developed with a multidisciplinary approach and represents a transparent review of the services provided by each centre. HNA members were involved in its development and are training and signing up to be reviewers with a good representation from across the UK.
The HNA was initially formed in the mid-1980s because nurses were experiencing the trauma of HIV/AIDS diagnoses and deaths. The HNA remains an organisation designed to support our members and provide forums for reflection and discussion. With the infected blood inquiry now underway, and at a time when staffing resources are tight across the UK, we recognise that our members are again working under stress. Therefore, in March 2019 we will again run a full annual conference, designed around a theme of wellbeing and resilience.
HNA meetings and courses are run by Haemnet, our education/research charity. In October 2017, the Contemporary Care of People with Bleeding Disorders course trained 16 participants from the UK and Ireland, and in October 2018 a cohort of 24 multidisciplinary professionals will head to Sheffield for the next course. This course is a unique, practical, hands-on educational opportunity developed and delivered by nurses and physiotherapists from key UK centres, supplemented by invited experts. It is the only course for nurses and physiotherapists specialising in the care of people with bleeding disorders.
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Also, in 2017 the ASPIRE clinical leadership development programme saw the second cohort of 6 nurses and allied care professionals from centres across the UK participate in three modules throughout the year. Other initiatives designed to enhance the level of practice and professionalism of nurses currently practising in the UK have included events designed to share experience with extended half-life products, and collaborative work on subcutaneous administration techniques. In addition, our members have participated in the Haemnet Horizons events, which facilitate collaborative work among nurses across Europe. We also have several on-going studies underway and hope shortly to begin collaborating with UKHCDO members on a study looking at pain.
We strongly believe that participation in our events greatly enhances the sense of community among HNA members and will go some way towards ensuring a happy, well-educated and sustainable haemophilia nurse establishment for the future. We recognise, however, that in recent years, many nurses have experienced difficulty in securing funding or study leave for educational courses and meetings. As a result, we have moved towards a model of centralised funding for our programmes, allowing us to keep the costs of attending courses down to a very low level, and where possible we make no charge at all; for some meetings we are also able to cover nurses’ travel costs, but we cannot do anything about study leave. We would strongly urge all centre directors to support their nurses in attending the educational opportunities that we are able to offer.
HNA members are key stakeholders in the ongoing care of people living with bleeding disorders; our members are playing an active role on new initiatives within the UK haemophilia treater community; including the CRG, CMU, the peer review group, and various UKHCDO working parties. The HNA committee wishes to thank all of the nurses who represent their colleagues on these groups. HNA members continue to bring passion to their roles, ensuring the national voice of haemophilia nursing is represented. Representation at Glasgow WFH 2018 showed the world what an amazing, passionate group of nurses we are. I am proud to be one of them.
Cathy Harrison, Chair, Haemophilia Nurses’ Association
September 2018
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18. Haemophilia Chartered Physiotherapists' Association
We aim to define, promote and encourage best practice for physiotherapy within haemophilia care, providing professional leadership and directing national physiotherapy policy.
Executive Committee
Anna Wells Chair: David Hopper Vice-Chair David Stephensen Research Lead Hannah Harbidge Secretary Joanne Minshall Treasurer
Research
Over the past 12 months HCPA members have continued to support and facilitate a thriving research and innovative environment. The annual meeting includes a half-day session focussed on sharing and developing research activity. As well as contributing joint score data to a multitude of observational and interventional studies, HCPA members have actively published and initiated several single and multi-centre musculoskeletal studies. Key papers published by the group this year include a thorough review of recent advances in musculoskeletal physiotherapy for haemophilia [Stephensen, Bladen & McLaughlin, Therapeutic Advances in Hematology; 2018; 9(8):227–237], and inter-rater reliability of physiotherapists performing the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol to evaluate synovitis and joint arthropathy [Stephensen, Classey, Harbidge, Patel, Taylor, Wells; Haemophilia; 2018; 24(3):471-476]. At the WFH Congress this year in Glasgow, three of the eight musculoskeletal abstracts selected for the free paper presentation session were submitted by UK physiotherapists. Hannah Harbidge presented a study evaluating the inter-rater variability of global gait score assessment using the HJHS criteria; Vishal Patel presented a paper reporting a novel physiotherapy-led musculoskeletal clinic for people with haemophilia and their perceptions of this clinic; and Steve Classey presented interim results of a real-world study on the use of point of care ultrasound imaging to guide treatment decision in people with haemophilia. Elizabeth Bradshaw will be presenting her work on measuring change following an acute bleed episode - what outcome measures do haemophilia patients think are of most value at the national Chartered Society of Physiotherapy 2018 congress. Based on this work, Elizabeth has secured funding from the NIHR Pre-doctoral Clinical Academic Fellowship scheme to develop a proposal to investigate the effectiveness of pulsed shortwave diathermy (PSWD) in the treatment of acute bleeds, with a view to conducting a trial researching home-based versus hospital based delivery.
NIHR Research Fellow, David Stephensen has led NIHR funding grants to investigate a feasibility study exploring the benefits of a muscle strengthening programme for children with haemophilia and a Novo Nordisk Access to Insight Clinical Research Grant to explore use of home ultrasound to empower the haemophilia patient to distinguish between bleeding and non-bleeding episodes. David Hopper will undertake a PhD linked to this work. Steve Classey has received a Pfizer Investigator Initiated Research grant to explore the use of point of care ultrasound imaging to guide treatment decision in people with haemophilia. Paul McLaughlin
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was successfully awarded a NIHR clinical doctoral research fellowship to complete a PhD in which he will investigate a rehabilitation intervention for the management of chronic arthritic joint pain in people with haemophilia. Paul McLaughlin in collaboration with Haemnet have received a Pfizer Investigator Initiated Research grant to bring together haemophilia professionals (nurses and physiotherapists) and personal trainers to develop a disease-specific fitness programme that can be delivered to young men with haemophilia to increase levels of participation in exercise and physical activity. Melanie Bladen was successfully awarded funding from the Sir William Coxen Trust to investigate the feasibility and sensitivity of using the i-STEP (an incremental step test standardised for height) to monitor physical function in boys with haemophilia.
An international collaboration led by the HCPA has been established to identify and standardise a core set of performance-based outcome measures of physical function in people with haemophilia (IPOP). The rationale for this work is based on the comprehensive evaluation and description of health recommendations of the World Health Organisation via the International Classification of Function (ICF) framework that suggest severity of health conditions are best described in terms of “Body Structures and Functions”, “Activities” and “Participation”. Activity reflects ability to perform daily tasks while participation reflects involvement in life situations. Current physical assessment of haemophilia focuses on joint structure, with little information on function or ability to perform and participate in activities. Furthermore, patients report little benefit from the HJHS in understanding their health. Standardising a core set of outcomes is necessary whilst minimising patient burden of multiple assessments. A consensus-based, decision analysis approach will be used to select the performance-based measures of physical function. This will be achieved through focus groups utilising Nominal Group Techniques as well as a series of online decision surveys.
In collaboration with the EAHAD Physiotherapy Committee, we have completed a survey of the role and scope of practice of haemophilia physiotherapists in Europe. This information will be used to establish principles of physiotherapy practice for people with haemophilia to support professional education strategies and self-governance of physiotherapists.
Anna Wells, Chair, Haemophilia Chartered Physiotherapists’ Association
September 2018
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19. BCSH Haemostasis and Thrombosis Task Force
Membership
Prof Mike Laffan Chair Dr Keith Gomez Secretary Dr Ian Jennings UK NEQAS representative Prof Isobel Walker UK NEQAS representative Dr Elaine Gray NIBSC representative Dr Raza Alikhan Dr Will Lester Dr Tina Biss Dr Deepa Arachillage Dr Julia Anderson UKHCDO representative Mr Sean Platton Mr Peter Baker
Professor Laffan and Dr Gomez continue for a second term as Chair and Secretary, respectively, from July 2018. The Task Force has met on 16th November 2017, 9th March 2018, 5th July 2018 and will meet on 20th October 2018 at the BSH Headquarters, London.
UKHCDO Guidelines Published 2017/2018
Hemlibra/ Emicizumab prescription and dosing: guidance from UKHCDO and NHSE. a UKHCDO Document, 2018.
Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee. PW Collins, R Liesner, M Makris, K Talks, P. Chowdary, E Chalmers, G Hall, A Riddell, C L Percy, C R Hay, D P Hart. Haemophilia 2018 24 344-347
Management of Inherited Bleeding Disorders in Pregnancy. S Pavord, B Madan, T Cumming, W Lester, E Chalmers, B Myers, H Maybury, C Tower, R Kadir. Green-top Guideline No. 71, published 27/04/17. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg71/
Guideline for the management of acute joint bleeds and chronic synovitis in haemophilia. J Hanley, A McKernan, M D Creagh (on behalf of the UKHCDO musculoskeletal working group). Haemophilia 2017 23 511-520.
UKHCDO protocol for the first line immune tolerance induction for children with severe haemophilia A: A protocol from the UKHCDO Inhibitor and Paediatric Working Parties. 01/02/17. P Collins, E Chalmers, J Alamelu et al. Haemophilia 2017 23 654-659
http://www.ukhcdo.org/wp-content/uploads/2017/01/ITI-protocol-2017.pdf
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BSH Guidelines Published 2017/2018
The use of viscoelastic haemostatic assays in the management of major bleeding. N S Curry, R Davenport, S Pavord, S V Mallett, D Kitchen, A A Klein, H Maybury, P W Collins, M Laffan. B J Haem 2018 182 (6) 789-806
Management of thrombotic and haemostatic issues in paediatric malignancy. K R Sibson, T T Biss, C L Furness, J D Grainger, R E Hough, C McCartney, J H Payne, E A Chalmers. B J Haem 2018 180 (4) 511-525
Guidelines in Preparation
The laboratory investigation of heritable disorders of platelet function. Andrew Mumford (chair), Keith Gomez, Tina Biss, Julia Anderson, Gill Lowe, Ian Jennings, Sean Platton, Peter Baker.
Prophylactic factor concentrate in children and adults with haemophilia A and B. Rachel Rayment and Tina Biss (co-chairs), Steve Austin, Liz Chalmers, Richard Gooding, Anne Kelly, Susie Shapiro, Kate Talks, Ollie Tunstall-Pedoe.
Laboratory aspects of assays used in haemostasis and thrombosis. Peter Baker (chair), Sean Patton, Ian Jennings, Paul Murphy, Elaine Gray, Claire Gibson, Mike Laffan. (Claire Gibson has joined the writing group representing BMS working in general haematology laboratories).
Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. A UK Haemophilia Centre Doctors' Organisation Good Practice Paper. K Gomez (chair), M Laffan, N Curry, P Lunt.
UKHCDO Guidelines Publications Policy
A UKHCDO Publication Policy has been written by Professor Makris and approved at the 57th Advisory Committee meeting on 7 September 2018. Any UKHCDO member or working party can propose a guideline title for approval by the Advisory Committee. Once the title is approved the member or working party decides on the membership of the group to produce the guideline and this is not restricted to UKHCDO members. Once the guideline has been completed it has to be approved by the UKHCDO Advisory committee before submission for publication. The title should include the fact that this is a UKHCDO guideline. The authorship should reflect the contributors to the guideline, provided they satisfy the international criteria for authorship. Membership of a working party does not mean automatic authorship on a guideline manuscript. It is recognised that not all UKHCDO Guidance will lend itself to the BSH guidelines process, but where possible it is preferable to have a guideline written and approved by BSH along with the mandatory audit template. Manuscripts that have followed the BSH process should be submitted to the British Journal of Haematology. Non-BSH approved guidelines, or those rejected by the British Journal of Haematology should be submitted to the Haemophilia journal. There is an agreement with both the British Journal of Haematology and the Haemophilia journal that all UKHCDO guidelines will be made freely available on publication. The UKHCDO website will link to the freely available manuscript as soon as it goes on line in early view at the
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journal website. Guidelines not intended for publication in a journal, as well as updates, will be published on the UKHCDO website and will be linked to the original guideline if one exists.
There are currently 20 UKHCDO guidelines and their status was discussed at the 55th Advisory Committee meeting on 19 January 2018. In accordance with the BSH process, each new guideline should incorporate an audit template. All current guidelines are reviewed against the BSH guidelines process which stipulates that those older than five years require formal review with a new literature search and consideration of updating or archiving. UKHCDO and BSH both fund literature searches. The 2005 publication titled: Framework for genetic service provision for haemophilia and other inherited bleeding disorders by CA Ludlam, KJ Pasi et al. has been archived, and the guidelines page updated in July 2018 to include the RCOG Greentop guideline No. 71.
Two Task Forces have been convened: the UKHCDO Gynaecology Task Force, chaired by Dr Nicky Curry, and the UKHCDO Laboratory Working Group, chaired by Dr Will Lester.
Dr Julia A M Anderson UKHCDO Representative for BSH Haemostasis & Thrombosis Task Force
September 2018
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20. Haemophilia Society WFH Congress 2018
Much of this year was dominated by preparations for hosting the World Federation of Hemophilia Congress in Glasgow from 20-24 May 2018. Congress was a huge success with 5110 delegates from 132 nations attending.
Newly Diagnosed Family Weekends
Hearing that your child has a bleeding disorder brings a huge range of emotions, for those who know they have a family history it often brings guilt for passing on the gene, or fear that your child will go through some of the devastating consequences your father or brothers experienced. For others the news is totally unexpected and comes along with questions about unexplained bruising. Social services involvement and fear for your baby and your family life. Our free weekends enable new parents to learn more about what to expect, meet others who are experiencing the same emotions and spend time hearing from and talking to experts helping them build a foundation of knowledge and support as they start their journey as a family. Specialist bleeding disorder physio’s, nurses, doctors, psychologists and social workers facilitate sessions alongside our local group representatives and youth ambassadors.
Youth Activities
This year we focussed our youth activities in summer camp in Surrey that reduced the isolation of living with a bleeding disorder, recognised the impact on siblings and raised confidence levels in our younger members.
From learning to give your treatment for the first time and understanding what your condition really means for you, to understanding how teamwork and determination can help you make huge leaps (literally in some cases), the campers loved every moment, even the torrential rain!
Youth Ambassador engagement
Our Youth Ambassadors are fundamental to our work, they attend many of our events and services, sharing their experiences, demonstrating treatment and offering a role model to younger members as well as reassurance to parents that a severe bleeding disorder won’t hold you back in life.
The first social for people aged 18-29, a trip to a comedy night in Leeds only attracted a few people but gave the foundations for the survey conducted slightly late to understand and increase youth involvement.
50 participants responded which the youth ambassadors used to evidence their request for funding for increased activity in 2018.
A youth ambassador also sits on the board now to regularly update the board on the work they have been doing.
Talking Red Programme
We began our Talking Red programme for women with bleeding disorders in 2014. This year almost 50 people came together at a weekend conference in Birmingham.
We discussed periods, surgery, nose bleeds and relationships. We shared an update on our first university Talking Red focus groups and the work of the EHC women’s committee.
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We also had a rallying cry from Talking Red ambassador Linda Wild, a social worker discussed support for women affected and held a breakout session for partners.
We had a stand at the fresher’s fair at University of Sheffield and had a footfall of 3,000 people.
Ageing
This year our aging project looked at how we could support our members with HIV and Hepatitis better, as well as focussing on staying well as you get older. Our conference looked at maintaining activity levels when you age, ensuring good dental health, as well as giving updates on new developments in HIV and Hep C treatment.
Inhibitor Project
We know that a diagnosis of an inhibitor takes a family from someone having a rare bleeding disorder that impacts daily life to an overwhelming situation where normal life seems far away and treatment, hospital trip and anxiety levels soar.
Our residential weekend in Leicester enabled 8 families of a child with an inhibitor and 3 adults with inhibitors to come together and hear from physiotherapists, psychologists and youth ambassadors as well as facilitated peer to peer sessions to share experiences and coping mechanisms. As members of the EHC inhibitors group we enabled one of our families to attend the European inhibitor summit. We also have a new inhibitor liaison rep who will be working with us to develop our services and advocacy as well as support other families with inhibitors.
Volunteering
We just couldn’t function without our incredible volunteers, Throughout the year over 30 healthcare professionals supported us at our events volunteering either for a day or an entire weekend, alongside hundreds of members who run our local groups and helped organise events across the country while youth ambassadors and talking red ambassadors have also volunteered at our events and educational days.
Advocacy
This year was dominate by our work focussed on access to new treatments for people with bleeding disorders. As members of the Clinical Reference Group in England (which is attended by Welsh and Scottish clinicians representatives too) we bring the collective patient voice along with two patients to provide advice to the decision makers in the NHS on what matters to our members about treatment, care and support. This included access to innovative new treatments, access to specialist nursing and physio care, and sharing people’s experiences at their haemophilia centres.
Public inquiry into infected blood
After so many years of campaigning, the community welcomed the announcement in July that there would be a full Statutory Public Inquiry. Our campaigning continued to ensure the responsibility for the Inquiry was removed from the Department of Health and Social Security and eventually this was changed to the Cabinet Office in late 2017.
The Trustee Board committed to funding of dedicated staff from a legacy, and subsequently a full-time position of Public Inquiry Lead was appointed and a dedicated Sub Committee of Trustees was formed to oversee the work on the Inquiry. A series of Roadshows was held with members around the UK to understand their expectations of the Inquiry and how they wanted to be represented by The Society.
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Sir Brian Langstaff was appointed as Inquiry Chair on the 8 February 2018. A consultation was opened on the Terms of Reference and using a range of channels, including a new social media group, we gathered opinions to inform our response to this Consultation.
Fundraising
Our fundraisers have continued to do amazing things for us this year, from hosting dinners to running marathons right through to abseiling down the Orbit Tower in the Olympic Park and golf days. We have also seen increased support from community groups such as the Freemasons (via donations and Ladies Nights). However, we are seeing a decline in people taking part in activities and hosting their own events. If we are to continue to provide the activities that we do, we hope to find new ways to engage with our community and the wider public and look to our members for new ideas and advice.
Liz Carroll, Chief Executive, The Haemophilia Society
October 2018
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21. Macfarlane Trust
As reported last year, in March 2017 the Minister announced that the NHS Business Services Authority (BSA) would take on the role of the new scheme administrator in England during 2017/18, along with similar organisations in the Devolved Administrations. At the time of writing last year’s report, it was expected that the transfer would take place on 1 November 2017; the transfer went ahead as anticipated on this date, and the majority of staff transferred to BSA under TUPE.
This meant that from 1 November 2017, the Department of Health (DH) ceased to fund the Macfarlane Trust to provide support to those with haemophilia who were infected with HIV as a result of contaminated blood products, and their families. However, as MFT has held reserves, the board decided to run two one-off grants programmes: one to provide grants for specialist equipment, and health-and mobility-related repairs and improvements to property, the other with the Honeycombe Memorial Fund to provide grants to bereaved partners and spouses to help them regain economic independence. Beneficiaries were invited to apply for grants in January 2018, with a closing date of 26 February 2018. The board then met at the end of March 2018 and agreed to award grants totalling approximately £450,000.
Once all of the grants have been paid to beneficiaries, and with no further funding being received for charitable activities, the board will need to consider a number of legacy issues, including when to wind up. This is likely to be by February 2018.
Jan Barlow, Chief Executive, The Macfarlane Trust
September 2018