Guide to
Focus
� Thrombophilia in Asian Countries:
Myth or Reality?
First Local Paper
� APCR test in the investigation of
thrombophilic state
Newsletter from All Eights
Announcing the
Haemostasis Symposium
& Workshop 2009,
24-25 of June,
Shangri-La Hotel, KL
Application
� System validation & correlation
protocols
Editor’s messages
Dear readers,
Welcome to the second edition of the Guide to Haemostasis Newsletter from All Eights.
In this issue, we are proud to cover some of the topics presented at the Stago Symposium at the 5th
Congress of the Asian Pacific Society on Thrombosis and Haemostasis, Singapore, 18 September 2008.
Stago together with professionals from various countries focused on Thrombophilia in Asian Countries –
from introduction of Thrombophilia to comparison between Thrombophilia in Western countries versus
Asian countries. They also explored the genetic risk factors for deep vein thrombosis among Japanese,
hereditary thrombophilia in Korea, normal ranges and estimated deficiency prevalence of antithrombin,
protein C and protein S in the general Chinese population.
All Eights is also proud to publish our first local paper submitted by Dr Wan Zaidah from HUSM. We are
extremely grateful for her contribution and hope to hear more from her as well as the local community.
We encourage our readers to submit their experiences either in technical or clinical aspects to share to the
community. If the article or paper is published, there will be a RM100 gift voucher for the contributor.
In the section on application, we focus on system validation and correlation protocols. These topics are
really relevant as users apply them frequently.
We also take this opportunity to announce that All Eights will organize a 2009 Haemostasis Symposium &
Workshop in Kuala Lumpur, under the auspices of Haemophilia Society of Malaysia and co-sponsored by
Diagnostica Stago. All Eights would like to extend a very warm welcome to all accepted to attend and
participate in this grand event. Due to logistics, limited seats are available.
We would like to thank all individuals who have contributed to the newsletter. We look forward to
continually provide you with future editions and welcome comments and input on the newsletter. Please
send to:
Marketing Department
ALL EIGHTS (M) SDN BHD
45, Jalan TS 6/10A, Subang Industrial Park,
47610 Subang Jaya, Selangor Darul Ehsan, Malaysia.
Tel: 603-5633 4988
Fax: 603-5633 0261
Email: [email protected]
Website: www.alleights.com.my
Best wishes,
Editorial team
FOCUSFOCUSFOCUSFOCUS
Stago Symposium at the 5th Asian-Pacific Society on Thrombosis and Haemostasis 2
Thrombophilia in Asian countries: Myth or Reality? 3
Thrombophilia in Western countries versus Asian countries 3
Hereditary Thrombophilia in Korea: What we learned from population and patients 4
Genetic risk factors for deep vein thrombosis among Japanese 4
Normal ranges and estimated deficiency prevalence of antithrombin, protein C and
protein S in the general Chinese population
5
APC-R test in the inverstigation of thrombophilic state 7
APPLICATIONAPPLICATIONAPPLICATIONAPPLICATION
Installation & Validation Guidelines for Coagulation Analyzers 9
� The Selection Process 9
� Method Validation 9
• Precision 9
• Linearity, Sensitivity and Reportable Range 10
• Accuracy 12
• System Correlation 12
• Reference Range Study 12
INFORMATION UPDATESINFORMATION UPDATESINFORMATION UPDATESINFORMATION UPDATES
Stago User Group Meeting 2009 – Haemostasis Symposium & Workshop 16
Pool Norm 18
STA-QCE International Haemostasis Proficiency Programme 19
CONTENTSCONTENTSCONTENTSCONTENTS
The symposium sponsored by Stago at the 5th Congress of the Asian-Pacific Society on Thrombosis and
Haemostasis held on 18th September 2008 in Grand Copthorne Waterfront Hotel, Singapore. The
symposium was chaired by Changgeng RAUN, MD, PhD from Suzhou University Medical College,
Suzhou, China and Nicole SCHLEGEL from Robert Debré Hospital and Paris7-Denis Diderot University,
Paris, France.
The topic for this symposium was about Thrombophilia in Asian Countries: Myth or Reality? This
symposium provided a great opportunity for everyone to exchange ideas and experiences in this field.
Professor Changgeng RUAN opened the symposium by stating “This symposium provided an advanced
overview of data on genetic risk factors for VTE from large series of subjects from three countries of
the Asia Pacific Area. These data should be helpful for the prevention and management of VTE patients
in this large geographic area”. This is followed by Doctor Nicole Schlegel’s comparison of the genetic
risk factors of VTE between western and eastern populations.
Three other speakers presented their cases as well. Professor Yongqiang Zhao, from Peking Union
Medical College Hospital, Beijing, China, presented the results of the largest prospective multicentric
STAGO SYMPOSIUM AT THE 5TH ASIAN-
PACIFIC SOCIETY ON THROMBOSIS AND
HAEMOSTASIS
survey establishing the normal ranges
and genetically determined deficiencies
of the three major natural anticoagulants
in the general Chinese population of Han
origin. Assistant Professor Hee Jin Kim,
from Samsung Medical Center and
Sungkyunkwan University School of
Medicine, Seoul, Korea, discussed the
results of her research on hereditary
thrombophilia in Korea, comparing VTE
patients to a large cohort of healthy
Korean people. Professor Toshiyuki
Miyata, from the National Cardiovascular
Center Research Institute, Osaka, Japan,
gave his speech on the genetic risk
factors for DVT among a very large series
of Japanese and gives a special light on
several aspects of protein S deficiency in
Japan.
The following pages contain brief
abstracts of each topic mentioned
above.
Venous thromboembolism (VTE) – deep vein thrombosis (DVT)
and pulmonary embolism (PE) – is a severe process which can be
triggered by a number of factors either acquired or genetic. VTE
is a major cause of mortality and morbidity in western
populations but is considered to be less frequent in eastern
populations. Geographic differences about the genetic risk
factors of VTE have been progressively established, showing that
two mutations, Factor V Leiden and G20210A mutation in Factor
II gene are frequent in VTE western patients but quite absent in
VTE eastern patients.
By Changgeng Ruan, Nicole Schlegel
Focus 2
Thrombophilia in Asian countries:
Myth or Reality?
Thrombophilia in Western countries versus
Asian countries
By Nicole Schlegel, MD, PhD from Robert Debré Hospital,
Paris, France
Venous Thromboembolism (VTE) is a unique thrombotic process, starting by
and abnormally expansive clot formation in a peripheral vein – deep vein
thrombosis (DVT) – and leading in more severe cases to the migration of
emboli towards the pulmonary artery, responsible for pulmonary embolism
(PE). The risk of VTE varies in the different surgical and medical settings but
the risk of death from PE is quite high. Thrombophilia is defined as a
tendency to VTE, either acquired or genetic. Various risk factors for VTE have
been identified. Their combined association and consequently the risk of
thrombosis increase with advancing age. The sites of thrombosis may be
suggestive of the origin acquired or genetic of VTE. An association of VTE with
arterial thrombosis in one patient is possible.
Previous studies have suggested that VTE was lower in Asians as compared to
Whites / Caucasians. However recent prospective multicentric studies form
large series show that VTE is not so rare in Asia, suggesting that VTE might
have been underestimated in these countries. Interestingly, genetic risk
factors for VTE differ in eastern and western populations. FV Leiden and
G20210A mutation in FII gene are the most common genetic risk factors in
western people but are quite absent in Asians. By contrast, deficiencies of the
three major natural anticoagulants, antithrombin (AT), protein C (PC) and
protein S (PS) seem very rare among whites as compared to Asians.
However, till recently, the prevalence of such deficiencies in Asia has been
estimated in small series only. New data from large series of several Asian
countries will be presented during this symposium. Thrombophilia associated
with AT deficiency was the first to be prescribed (Egeberg O, 1965), followed
by PC and PS deficiency. The molecular basis for these deficiencies has been
characterized and a number of genetic variants are known. The risk for VTE
varies according to the genotype. The origin of a difference in the VTE rate
and the genetic-related diversity between western and eastern populations
might be explained by a genetic drift or natural selection. The phylogenic,
genetic and environmental factors of these differences are discovered
progressively owing to studies of populations from different geographic areas
and to new sophisticated genetic tools.
Acquired risk factors
Old age
History of VTE
Immobiliz, plaster c
Surgery, trauma
Cancer
Myeloprolif, Disorders
Polycythemia vera
Antiphospholipid Syndrome
Hormonal treatment
Central venous KT
Obesity
Main genetic risk factors
Function loss
Antithrombin (AT)
deficiency
Protein C (PC) deficiency
Protein S (PS) deficiency
Function gain
Factor V mutations: Leiden
Factor II mutations:
G20210A
Others
Dysfibrinogenemia
FXIII 34val
Other risk factors*
Hyperhomocysteinemia
High levels of FVIII
High levels of FIX
High levels of FXI
High levels of fibrinogen
APC resistance in the
absence of FV. Leiden
High / low levels of TAFI?
High levels of PC inhibitor
* Possible genetic regulation
Focus 3
Venous Thromboembolism (VTE) has long been
considered to be rare in Asian countries. However,
data from a couple of recent studies challenged this
belief, warranting a revisit to the epidemiology of VTE
and its risk factors including genetic defects leading to
hereditary thrombophilia (HT), in particular, VTE and
HT have, no doubt, under-recognized in Korea. From
personal experience, the introduction of molecular
genetic tests as a routine 2nd-line laboratory workup
has greatly facilitated the accurate diagnosis of HT. on
the other end, population screening revealed at least
0.72% of Korean population have HT (protein C/S
[PC/PS] or antithrombin [AT] deficiency). Of note, AT
deficiency was more common than PC or PS
deficiency. It was also more common than PS
deficiency among VTE patients; however, the
mutation spectrums were strikingly different,
suggesting different penetrance of mutations and the
Great efforts are needed to increase the awareness of
VTE and HT in Asian countries, and this could be
achieved by rigorous collection of evidences and
active communication among healthcare providers
and also with the general population.
Hereditary Thrombophilia in Korea:
What we learned from population and patients
By Hee-Jin Kim, MD, PhD from Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Korea
Genetic risk factors for deep vein thrombosis among Japanese
By Toshiyuki Miyata, PhD from National Cardiovascular Center, Suita, Japan
There is mounting evidence that mutations associated
with a given disease arise with different frequencies
among ethnic groups, thus ethnicity-specific studies
are needed to identify causative mutations and
properly assess risk. We evaluated the genetic
contribution to venous thromboembolism (VTE) in
Japanese and found that protein S mutation K1986E is
a genetic risk factor. We estimated allele frequency to
be 0.009, suggesting that 1 out of 12,000 Japanese
may be homozygous for the E allele, thus possibly as
many as 10,000 individuals. We intensively sequenced
PROC, PROS1, SERPINC1, in 173 Japanese patients
with VTE and found that about 30% carried
nonsynonymous mutations. Mutation carriers
showed early onset of VTE compared to non-
carriers. Carriers should avoid environmental risk
factors known to be associated with VTE.
Focus 4
This largest multicentric prospective survey in the
healthy adult Chinese was aimed to determine the
normal ranges of antithrombin (AT), protein C (PC) and
protein S (PS), the prevalence of their plasma deficiency
and the genetic variants. 3493 healthy adult Chinese
(1734 men / 1759 women) were included. Men showed
higher levels of PC (p=0.03) and PS (p<0.0001) than
women when adjusted to age. In women, mean PC and
PS activity increased with increasing age. However, in
men, mean PC activity levels increased with age up to
49 years (p<0.0001) but decreased after 50 years
(p<0.0001) and mean PS activity levels significantly
decreased after 50 years of age. AT activity plasma
levels over time were no significant changes in women,
but decreased in men and more importantly after 50
years of age. A genetic variant was found in 15
individuals: 3 in SERPINC gene (0.08%), 9 in PROC gene
(0.25%), and 2 in PROS1 gene (0.057%). Among the 15
mutations, 6 were novel. The clinical relevance of
statistically significant variations of the three proteins
with age and gender should be further discussed in
such a large series of subjects. It should be considered
when evaluating the thrombotic risks or events in the
Chinese population.
Normal ranges and estimated deficiency prevalence of antithrombin,
protein C and protein S in the general Chinese population
By Y. Zhao, MD, PhD from Peking Union Medical College Hospital,
Beijing, China
Focus 5
APC-R test in the Investigation of
Thrombophilic State
By Dr Wan Zaidah from Hospital Universiti Sains Malaysia
Activated protein C resistance (APC-R) state can be due
to acquired or inherited disorders. This condition is
closely associated with thrombophilic state leading to
commonly venous thrombosis. Anti-phospholipid
syndrome, deficiency of protein C, S and anti-thrombin
are the most common causes investigated in thrombotic
disorders. Haemostatic investigations for thrombophilia
include protein C, protein S, antithrombin
activity/antigen assays, lupus anticoagulant study and
APC-R test. Thrombosis is the outcome of multiple
contributing factors and hence the above mentioned
factors might be compounded with other conditions
such as hyperhomocysteinaemia, high factor VIII levels
and etc. however, about 30-40% of cases were reported
as no detectable abnormality from the routine
thrombophilia investigation.
APC-R test is used as a screening tool for the presence of
hereditary cause of APC-R state which is commonly due
to factor V Leiden (FVL) mutation. This condition has
been reported to be high among Caucasian with the
incidence of around 5-15% of the population. Although
this condition is said to be rare in Malaysian population,
FVL mutation has been reported and diagnosed among
patients with venous thrombosis.
A small study among 71 healthy Indians was conducted
in Universiti Sains Malaysia to detect this mutation. Four
individuals were found to have heterozygous state of
FVL mutation in this study group. APC-R test is a reliable
screening test for this mutation especially in centers
where mutation analysis is not available. APC-R test is a
simple and sensitive test to detect FVL mutation. It is a
useful test to be included in thrombophilia study where
facilities for molecular study are not available.
This test can also be used as a screening method
before DNA analysis. FVL mutation was reported in
Malays with low prevalence. Malaysia is a
multiracial country in which inter-racial marriages
are common thus this gene can be transmitted to a
new generation. APC-R test can be done by most
coagulation analyzers. Although this test has a role
to diagnose APC-R state, the interpretation of the
result needs to be done carefully taking into
consideration the pre-analytical factors, reagents
and analyzers. This test can be done on patients
taking warfarin (by using Factor V deficient plasma
reagent in the test procedure) but the clotting time
will be interfered in patients taking heparin or
having coagulation inhibitors. Confirmatory test
with DNA study is recommended for cases with
positive or borderline APC-R results or when
coagulation based test is not suitable to be done
due to the above mentioned reasons.
The significance of detecting APC-R state other
than FVL mutation has not been shown clearly from
the previous studies. Detection of APC-R state in a
person without having clinical significance is
doubtful and therefore the test is indicated only
when the finding is useful for patient’s
management and in high risk family members. In
conclusion, APC-R test is useful test in the
investigation of thrombophilia and applicable to
our setting as this generic risk for venous
thrombosis exists in our population.
Our deepest gratitude to Dr Wan Zaidah, HUSM, for submitting our first local paper
Local Paper 7
Installation & Validation Guidelines for
Coagulation Analyzers
The purpose of this issue is to establish guidelines for
the installation and the validation of STA® Coagulation
analyzers.
The Selection Process
Issues that need to be addressed when selecting a
coagulation analyzer include:
• Principle / Method
• Interference due to icteric & lipemic samples
• On-board quality control programs
• Autodilution methodology
• Bi-directional interface capability
• Reagent and sample inventory monitoring
• Patient and reagent barcode capabilities
• Stat testing capability
• Number of assays the analyzer is able to
perform simultaneously
• Availability of chromogenic, clot detection
and immunologic (latex immunoassay)
methodologies
• Ease of use
• Ease of maintenance
• Rate of sample throughput
• Availability of cap piercing
• Automation availability (robotics)
Reagents Selection:
• Note the reagent abilities to detect factor
deficiencies & coagulation inhibitors.
• The selection of Prothrombin Time (PT) and
Activated Partial Thromboplastin Time (APTT)
reagents should be decided according to
anticoagulant therapy monitoring.
Finally but not least, the quality of technical support
teams from the vendors should be considered. Having
easy access to company personnel who are capable to
perform necessary method validation procedures
required by regulatory agencies is very helpful to
laboratory technologists and pathologists.
Method Validation
The validation is determined in compliance with
Clinical Laboratory Improvement Amendments of 1988
requirements for verification of precision, sensitivity,
reportable range, correlation, accuracy and reference
ranges.
The method validation testing is standardized and
applies onto PT, APTT, Fibrinogen, D-Dimer, Thrombin
Time, Reptilase, Factor assays, Protein C, Protein S,
Antithrombin III, Antiplasmin, Plasminogen, Heparin
assay and Lupus Anticoagulant.
Precision
• To assess the reproducibility of each assay on the
instruments, 20 normal and 20 abnormal controls
were assayed consecutively without interruption
Application 9
Analyte Intra-run Precision Inter-run Precision (QC)
CV SD CV SD
NL AB NL AB NL AB NL AB
Prothrombin time ≤ 2.5 ≤ 2.5 NA NA ≤ 5.0 ≤ 5.0 NA NA
APTT ≤ 2.5 ≤ 2.5 NA NA ≤ 5.0 ≤ 10.0 NA NA
Fibrinogen ≤ 5.0 ≤ 8.0 NA NA ≤ 10.0 ≤ 10.0 NA NA
D-Dimer NA NA ≤ 0.1 ≤ 0.2 NA NA ≤ 0.2 ≤ 0.4
Antithrombin III ≤ 10.0 ≤ 10.0 NA NA ≤ 20.0 ≤ 20.0 NA NA
Protein C ≤ 10.0 ≤ 10.0 NA NA ≤ 20.0 ≤ 20.0 NA NA
Protein S ≤ 10.0 ≤ 10.0 NA NA ≤ 20.0 ≤ 20.0 NA NA
Plasminogen ≤ 10.0 ≤ 10.0 NA NA NA NA NA NA
Antiplasmin ≤ 10.0 ≤ 10.0 NA NA ≤ 20.0 ≤ 20.0 NA NA
Reptilase time ≤ 5.0 ≤ 5.0 NA NA ≤ 10.0 ≤ 10.0 NA NA
Thrombin time ≤ 5.0 ≤ 5.0 NA NA ≤ 10.0 ≤ 10.0 NA NA
Heparin assay NA NA ≤ 0.1 ≤ 0.1 NA NA ≤ 0.1 ≤ 0.1
vWF ≤ 10.0 ≤ 10.0 NA NA ≤ 20.0 ≤ 20.0 NA NA
Extrinsic Factor ≤ 10.0 ≤ 10.0 NA NA ≤ 20.0 ≤ 20.0 NA NA
Intrinsic Factor ≤ 10.0 ≤ 10.0 NA NA ≤ 20.0 ≤ 20.0 NA NA
APTT: Activated Partial Thromboplastin Time; vWf: von Willebrand factor; NA: Not Available; NL: Normal; AB: abnormal
Table 1: Coagulation system method validation acceptance criteria
Citation from “Selection and implementation for coagulation instruments/reagents in a multiple hospital/clinic network”,
Blood Coagulation and Fibrinolysis 2000, 11:599-608. Revised by Stago on 1/02. 4/02, 2/06, 8/06, 9/06.
(intra-run precision). These controls were once
again assayed over a 5-day period and randomly
for four data points per day to evaluate day-to-
day variation (inter-run precision). Intra- and
inter-run precision assess the random analytical
error of the system.
• Refer to Table 2 & Table 3, the data were
analyzed by determining the mean (x), standard
deviation (SD) and coefficient of variation (CV).
The CV would be utilized to assess precision in all
tests except the D-dimer. In this case, the SD
would be utilized because it is the best indicator
of precision performance. When the D-dimer is
reported as less than a whole number (i.e. 0.2)
the CV is no longer a useful tool because it
becomes mathematically inflated CV = SD / x
(100). Refer to Table 1 for the analyte acceptance
criteria.
Linearity, Sensitivity and Reportable Range
In coagulation testing, linearity, sensitivity, and
reportable range are closely related. It is required by
CAP that each laboratory assesses and validates the
linearity of all assays that it intends to perform.
Based upon linearity and sensitivity studies, the
reportable range of an analyte is determined.
Westgard defines linearity, sensitivity, and
reportable range as follows:
• Linearity: The measure of the degree to which a
curve approximates a straight line. The linearity
of a system is measured by testing levels of an
analyte that are known relative to each other.
• Sensitivity: Minimal limit of quantification. The
functional sensitivity is used to refer to an
estimate of the detection limit that is calculated
from replicate measurements of low-
concentration patient samples.
Application 10
Table 2:
Intra-run precision using normal pool plasma
Table 3:
Inter-run precision using normal pool plasma
Reagent STA-Neo
Cl Plus
STA-PTT A STA-Fib 2 Reagent STA-Neo Cl
Plus
STA-PTT A STA-Fib 2
No PT (sec) APTT (sec) Fib (g/l) No PT (sec) APTT (sec) Fib (g/l)
1 13.8 34.8 2.93 1 13.0 35.5 3.30
2 13.9 34.3 2.80 2 13.4 35.4 3.47
3 13.9 34.6 2.95 3 13.7 35.0 3.47
4 13.9 34.3 2.91 4 13.9 34.9 3.57
5 13.9 33.7 2.91 5 13.3 34.3 3.42
6 13.7 34.1 2.84 6 12.8 33.9 3.35
7 13.6 34.2 2.89 7 13.4 35.3 3.42
8 13.8 33.6 2.72 8 13.3 34.2 3.40
9 14.0 33.8 2.86 9 13.2 33.9 3.26
10 14.0 34.8 2.73 10 12.2 34.1 3.24
11 13.9 34.4 2.86 11 13.1 35.4 3.37
12 13.7 34.0 2.77 12 13.2 34.4 3.21
13 13.8 33.6 2.79 13 13.2 30.7 3.13
14 13.8 34.2 2.82 14 13.6 34.1 3.33
15 13.8 34.0 2.70 15 13.7 35.8 3.30
16 14.1 34.2 2.75 16 13.9 35.2 3.15
17 13.8 34.0 2.86 17 13.4 35.4 3.26
18 13.8 35.5 2.75 18 13.2 33.9 3.30
19 13.8 34.0 2.82 19 13.4 33.9 3.35
20 13.9 34.4 2.68 20 13.1 33.8 3.28
N: 20 20 20 N: 20 20 20
Mean: 13.85 34.23 2.82 Mean: 13.30 34.46 3.33
SD: 0.11 0.46 0.08 SD: 0.39 1.11 0.11
CV (%): 0.83 1.33 2.83 CV (%): 2.91 3.22 3.31
Table 2 and Table 3: Example data for both Intra-run and Inter-run precision using normal pool
plasma
Application 11
• Reportable range: The range of concentration
of the substance in the specimen for which
method performance is reliable and test results
can be reported (the lowest and highest test
results that are reliable and can be reported).
Linearity in this validation process was assessed
within the context of the assay’s standard curve.
The evaluation was based upon the correlation
coefficient (r) and the standard curve point values
versus the recovered values as translated from the
actual curve. The r-value must have been greater
than 0.980 and the recovered values must have
been within 10% of the standard values. Once the
linearity of an assay was validated within the
standard curve, the reportable range was
determined by setting up automatic re-dilution
conditions at the highest standard curve point and
at the lowest standard curve point. The redilute
conditions would have higher dilutions for values
that exceed the highest point on the curve; likewise,
lower dilutions would be for values that are lower
than the lowest point of the curve. This lowest point
the curve was also used to define the sensitivity of
the assay.
Accuracy
• The accuracy of an assay may be defined as the
closeness of the agreement between the result
of a measurement and a true value of the
measurement.
• Accuracy was evaluated by method comparison
between the existing instrument/reagent
system and the new instrument/reagent
system. The selection of samples was important
to the method comparison.
• The percentage of recovery is calculated by
using mean of new system compare to existing
system (the target value).
System correlation
• The purpose of this procedure is to ensure the
most homogeneous possible distribution of
values between the two analyzers i.e. existing
unit and the newly installed unit.
• At least 30 specimens are collected for the
measurement.
• The collected specimens should span the entire
physiological range, which consisted of normal
specimens, low, mid and high range specimens
as well.
• By using same lot number of reagents and
prepared freshly, the specimens should be run
on both analyzers within 2 hours.
• The existing instrument is plotted on the x-axis
whereas the new instrument is plotted on the
y-axis. The R value, slope & intercept % were
analysed for comparison.
• The results were analyzed by linear regression.
Comparison between identical instrument and
reagent systems is shown in Table 4.
Reference Range Study
• The purpose of this procedure is to establish
laboratory’s own expected reference range.
Reference range varies from one laboratory to
another laboratory, depending on reagents,
instrument and method in use.
• At minimum of 20 healthy donors are collected.
A greater number of donors increase the
reliability of reference interval.
• The donors could not be on medication, such as
Coumadin, heparin, antibiotics, birth control or
estrogen-containing drugs, and could not have
any known immunological conditions. A group
of donors should represent a wide span of ages,
ethnic groups and gender.
• Samples to be tested are collected fresh and
tested for each parameter tested. The study
can be carried out over a period of several days
to minimize day-to-day variations.
• The results were analyzed for their distribution
with the Gaussian Law. Mean (x) and standard
deviation (SD) were calculated to determine the
reference range. Reference range is the range
of mean +/- 2SD.
Application 12
Analyte System Correlations
R value Slope Mean Bias (%) from
Average*
Prothrombin time ≥ 0.95 0.9 – 1.1 ± 5
INR ≥ 0.95 0.9 – 1.1 ± 10
APTT ≥ 0.95 0.9 – 1.1 ± 8
Fibrinogen ≥ 0.95 0.9 – 1.1 ± 10
D-Dimer ≥ 0.95 0.9 – 1.1 ± 20
Antithrombin ≥ 0.95 0.8 – 1.2 ± 15
Antiplasmin ≥ 0.95 0.8 – 1.2 ± 15
Extrinsic Factors ≥ 0.95 0.8 – 1.2 ± 15
Instrinsic Factors ≥ 0.95 0.8 – 1.2 ± 15
Heparin assay ≥ 0.95 0.8 – 1.2 ± 15
Plasminogen ≥ 0.95 0.8 – 1.2 ± 15
Protein C ≥ 0.95 0.8 – 1.2 ± 15
Protein S ≥ 0.95 0.8 – 1.2 ± 15
Reptilase time ≥ 0.95 0.8 – 1.2 ± 8
Thrombin time ≥ 0.95 0.8 – 1.2 ± 8
vWF ≥ 0.95 0.8 – 1.2 ± 15
* The Mean Bias (Mean Difference) % is calculated using the following formula:
(Mean of Raw Differences/Mean of Averages) x 100
Table 4: Comparison between Identical Instrument and Reagent Systems
Citation from “Selection and implementation for coagulation instruments/reagents in a multiple hospital/clinic
network”, Blood Coagulation and Fibrinolysis 2000, 11:599-608. Revised by Stago on 1/02. 4/02, 5/02, 6/02, 4/03,
1/05, 2/06, 8/06.
Application 13
No ID Existing Instrument New Instrument 1 A153210 29.30 31.90 2 A176484 35.00 38.00 3 B085141 49.60 52.10 4 A192871 55.30 59.20 5 B375258 62.10 54.90 6 B031423 43.60 49.40 7 B311606 139.10 141.90 8 B345764 38.10 41.50 9 B357497 37.80 41.50
10 A007049 48.80 50.40 11 A009531 55.10 57.10 12 B357400 36.10 37.40 13 B377795 48.10 56.50 14 B064352 29.30 33.50 15 B320105 36.50 38.50 16 A075870 41.90 48.50 17 B177386 91.60 106.60 18 A017771 38.90 42.10 19 B216373 46.30 48.90 20 B377138 38.20 41.70 21 B367828 56.60 57.70 22 A050776 38.00 39.80 23 A935732 43.10 43.30 24 A113135 52.80 54.70 25 B335599 44.90 48.70 26 A019598 45.00 45.60 27 B297899 55.80 59.40 28 B377812 39.70 40.90 29 B357132 46.90 50.90 30 A006698 139.70 121.90
y = 0.9274x + 6.1605
R² = 0.9644
R=0.982
0.00
20.00
40.00
60.00
80.00
100.00
120.00
140.00
160.00
0.00 20.00 40.00 60.00 80.00 100.00 120.00 140.00 160.00
Ne
w In
stru
me
nt
Existing Instrument
Correlation of APTT between Existing Instrument and New
Instrument
Table 5: Example data for Correlation of APTT between Existing Instrument and New Instrument
Application 14
DATE: 24 DATE: 24 DATE: 24 DATE: 24 –––– 25 JUNE 200925 JUNE 200925 JUNE 200925 JUNE 2009
VENUE: SHANGRIVENUE: SHANGRIVENUE: SHANGRIVENUE: SHANGRI----LA HOTEL, LA HOTEL, LA HOTEL, LA HOTEL, KUALA LUMPURKUALA LUMPURKUALA LUMPURKUALA LUMPUR
Haemostasis Symposium &
Workshop 2009
International buffet
Free WiFi
Free shuttle service
to famous
landmarks in KL
Under the auspices of Hemophilia Society of Malaysia, All Eights (M) Sdn Bhd in
conjunction with Diagnostica Stago will be organizing a Haemostasis Symposium &
Workshop 2009 on 24th
– 25th
of June which falls on Wednesday and Thursday. This
event will be held at the Shangri-La Hotel, Kuala Lumpur. We cordially invite our Stago
users / customers to join our user group meeting and enjoy the event.
The theme for this event will focused on Paediatric Haemostasis and Accreditation &
Quality Assurance. Overseas speakers as well as local haematologists will be presenting
and lecturing at this symposium. The workshop on accreditation and quality assurance
will be on the second day.
This is a great opportunity for you to expand your knowledge and further your
experience in this field. Please grace us with your presence and do not forget to bring
your laptop along for the data interpretation during the workshop. We look forward to
seeing you there.
Regards,
Organizing committee
Information Updates 16
Information Updates 17
25 JUNE 2009, THURSDAY
Sabah Room
0800 – 0845
ISO 15189
Dr Jamilah Bt Baharom, Penang Hospital, Malaysia
0845 – 0915
Lupus Anticoagulant Diagnosis. Pool Norm: A new helpful tool
Dr Patricia Roger, Diagnostica Stago, France
0915 – 0945
Role of IQC and EQA in laboratory performance
Dr Patricia Roger, Diagnostica Stago, France
0945 – 1030
Topic and speaker to be advised
1030 – 1100
Tea break
1100 – 1200
Workshop: ISI Verification – Discussion & Result Interpretation
Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia
Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia
1200 – 1300
Workshop: APTT Sensitivity to Heparin
Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia
Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia
1300 – 1400
Lunch
1400 – 1500
Workshop: APTT Sensitivity to Heparin -Discussion & Results Interpretation
Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia
Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia
1500 – 1600
APTT Sensitivity to Factors - Discussion & Results Interpretation
Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia
Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia
1600 – 1630
Tea Break
1630 – 1700
Discussion & Conclusion of Workshop
24 JUNE 2009, WEDNESDAY
Sarawak Room
0800 – 0845
Registration
0845 – 0900
Welcome & opening address
0900 – 0945
Topic and speaker to be advised
0945 – 1045
Thrombosis and Thrombophilia in Children
Dr Nicole Schlegel, Robert Debré Hospital, France
1045 – 1115
Tea break
1115 – 1200
Haemostasis in Neonates
Dr Jameela Sathar, Ampang Hospital, Malaysia
1200 – 1300
Establishing Paediatric Reference Range
Dr Vera Ignjatovic, Royal Children’s Hospital, Australia
1300 – 1400
Lunch
1400 – 1500
Acquired and Inherited Platelet Disorders in Children
Dr Nicole Schlegel, Robert Debré Hospital, France
1500 – 1600
Heparin Therapy In Children
Dr Vera Ignjatovic, Royal Children’s Hospital, Australia
1600 – 1630
Tea Break
1630 – 1700
Outpatient management of anticoagulant therapy. Heparin
and Warfarin monitoring.
Dr Patricia Roger, Diagnostica Stago, France
1700 – 1730
Customer feedback forum with All Eights and Stago
Pool Norm
For safe clinical direction
(Cat No. 00539)
Pool containing a minimum of 20 normal human plasmas, rigorously selected, based on a complete haemostasis workup
Ordering Information:
Cat No. Description Packing
00539 Pool Norm 12 vials
Contact Mr Eric Teo (016-982 0048)
Normal human plasma pool perfectly suited for
the screening of Lupus Anticoagulants (LA)
• For the mixing study (1:1 mixture of patient and reference plasma)
� Reliable differentiation between a coagulation factor deficiency and the presence of a LA
• For the normalized ratio calculation
� Reference plasma for STA®-Staclot® DRVV Screen and STA®-Staclot® DRVV Confirm
EASY TO USE
o Suitable to all laboratories, regardless of their level of activity
SAFE
o Biological security: Pool Norm made from human plasma which
tested negative for HIV, HCV and Hepatitis B
o Analytical security: Specifications adapted to its use in LA
screening, clinical validations with all Stago reagents for LA
evaluation and factor deficiencies
REPRODUCIBILITY
o Strict plasma selection that guaranties reproducibility batch to
batch
VALIDATED
o To be used with various cephalins: PTT-LA / STA®-PTT Automate,
STA®-Cephascreen® / STA®-C.K. Prest®
o To be used for DRVV testing with STA®-Staclot® DRVV Screen /
STA®-Staclot® DRVV Confirm
Information Updates 18
IINNTTEERRNNAATTIIOONNAALL HHAAEEMMOOSSTTAASSIISS
PPRROOFFIICCIIEENNCCYY PPRROOGGRRAAMMMMEE
EXTERNAL QUALITY
ASSESSMENT (EQA)
� Assesses the performance
of laboratory testing
systems
� Complements the internal
Quality Control
� Ensures harmonization of
results and comparability
between laboratories
� Identifies possible
deficiencies in laboratory
practice
� Increase results confidence
and patient safety
� Helps to answer to
regulatory requirements
� Collects information for
laboratory accreditation
purposes
Dedicated @ QCE website for
submission and view reports
www.stagoqce.com or
www.stago.com
For all STA-Compact / STA-Compact CT User
STA®-QCE is an International Program for Stago Systems. STA®-
QCE has provided you with international haemostasis external
quality assessment programs since 1998. It has more than 1,500
participants worldwide in over 50 countries.
Stago supplies twice a year with 2 levels of STA®-QCE. It includes
routine and speciality tests: PT, APTT, Fibrinogen, Factors, AT,
Protein C, Protein S, D-Dimer, vWF, Heparins.
Ref. Designation Content Packaging
00995 STA®-QCE 1&2
(May)
3 vials of STA®-QCE 1 6 x 1 ml
3 vials of STA®-QCE 2 6 x 1 ml
00996 STA®-QCE 3&4
(November)
3 vials of STA®-QCE 3 6 x 1 ml
3 vials of STA®-QCE 4 6 x 1 ml
For this season, STA®-QCE 2009-1 & 2 is available from now. To
those who wish to join this cycle, please do not hesitate
to contact Ms. Yunnie Tan at this number 012-3735391.
Clear Reports
� A report with the complete results: We analyze the
results test by test and we give the statistical
distribution of the results
� A customized form with the name of the laboratory, the
instrument used, and three tables
� A “Youden Plot” graph for each test performed by the
laboratory
� Laboratory results Recap which summarizes the results of
the last 5 participations of the laboratory
Information Updates 19
Are you interested to contribute in this
newsletter publication?
If you have any technical or clinical experience in this field that you wish to share with
everybody, please do not hesitate to contact us directly. As a token for your contribution,
we would like to award the contributor with RM100 gift voucher on publication.
Any comment or input, please send to:
Marketing Department
ALL EIGHTS (M) SDN BHD
45, Jalan TS 6/10A, Subang Industrial Park,
47610 Subang Jaya, Selangor Darul Ehsan, Malaysia.
Tel: 603-5633 4988
Fax: 603-5633 0261
Email: [email protected]
Website: www.alleights.com.my
Contribution 20
ALL EIGHTS (M) SDN BHD
45, Jalan TS 6/10A, Subang Industrial Park, 47610 Subang Jaya,
Selangor Darul Ehsan, Malaysia.
Tel: (603) 5633 4988 Fax: (603) 5633 0261
Email: [email protected] Website: www.alleights.com.my
ALL EIGHTS (S) PTE LTD
6, Harper Road, #03-02 & #06-07 Leong Huat Building,
Singapore 369674
Tel: (65) 6288 6388 Fax: (65) 6284 9805
Email: [email protected] Website: www.alleight.com
Poster available from All Eights
