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Assessment of Assessment of perioperative bleeding riskperioperative bleeding risk
When to look furtherWhen to look further
A critical balanceA critical balance
Bleeding riskBleeding risk Type of operationType of operation Consequences of excessive bleedingConsequences of excessive bleeding
? Widespread preoperative screening? Widespread preoperative screening ExpenseExpense False positivesFalse positives Procedures delayedProcedures delayed
Conditions not to missConditions not to miss
Haemophilia AHaemophilia A Haemophilia BHaemophilia B Von Willebrands diseaseVon Willebrands disease Deficiency of Factor VII, VIII, IX, X, XIDeficiency of Factor VII, VIII, IX, X, XI Factor specific inhibitorsFactor specific inhibitors Platelet dysfunctionPlatelet dysfunction Hypofibrinoginemia/Hypofibrinoginemia/
dysfribrinoginemiadysfribrinoginemia
Operations not to missOperations not to miss
IntrtacranialIntrtacranial SpinalSpinal TonsillectomyTonsillectomy Cancer related surgeryCancer related surgery
History is absolutely History is absolutely criticalcritical
Guides the need for Guides the need for laboratory investigationslaboratory investigations
Clinical CluesClinical Clues
Previous surgical bleedingPrevious surgical bleeding TransfusionTransfusion Return to theatreReturn to theatre Readmission for haematoma/bleedingReadmission for haematoma/bleeding
History of significant spontaneous History of significant spontaneous bleedingbleeding Recurrent epistaxis , recurrent GIT Recurrent epistaxis , recurrent GIT
bleedingbleeding Haemarthrosis, retroperitoneal bleeding, Haemarthrosis, retroperitoneal bleeding,
muscle bleedsmuscle bleeds
Clinical cluesClinical clues
MenorrahgiaMenorrahgia Floods, clots, period> 7 days, home from Floods, clots, period> 7 days, home from
school/workschool/work Iron deficiencyIron deficiency Hysterectomy for menorrhagiaHysterectomy for menorrhagia
Post partum bleeding not due to obstetric Post partum bleeding not due to obstetric causescauses
Petechia, easy bruisingPetechia, easy bruising
Family historyFamily history
Bleeding disorderBleeding disorder Deaths from ICHDeaths from ICH Surgical Bleeding – Transfusion, Surgical Bleeding – Transfusion,
return to theatre return to theatre Detailed historyDetailed history
Prompts- circumcisionPrompts- circumcision Tonsillectomy, appendicectomyTonsillectomy, appendicectomy fracturesfractures
DrugsDrugs
Antiplatelet agentsAntiplatelet agents AnticoagulantsAnticoagulants Drugs associated with Drugs associated with
thrombocytopeniathrombocytopenia Herbal medicationsHerbal medications
GarlicGarlic GinsengGinseng Ginko biloba Ginko biloba
Laboratory screenLaboratory screen
FBEFBE PT/APTT/fibrinogenPT/APTT/fibrinogen vWF AgvWF Ag Platelet aggregometryPlatelet aggregometry
Abnormal coagulation testsAbnormal coagulation tests
Prolonged APTTProlonged APTT Any prolongation Any prolongation ? Corrects on mixing – factor deficiency? Corrects on mixing – factor deficiency ? Fails to correct- factor specific inhibitor ? Fails to correct- factor specific inhibitor
or non specific inhibitoror non specific inhibitor Liver function testsLiver function tests heparin like drugsheparin like drugs DICDIC
Prolonged APPTProlonged APPT
Mixing studiesMixing studies Corrected mixCorrected mix
Factor assays VIII, IX, X, XI XIIFactor assays VIII, IX, X, XI XII Liver functionLiver function Vit KVit K
Non corrected mixNon corrected mix Lupus anticoagulantLupus anticoagulant Factor specific inhibitorsFactor specific inhibitors
Abnormal coagulation testsAbnormal coagulation tests
Prolonged PTProlonged PT Any prolongation Any prolongation ? Corrects on mixing – factor deficiency? Corrects on mixing – factor deficiency ? Fails to correct- factor specific inhibitor? Fails to correct- factor specific inhibitor LFTS, LFTS, Warfarin,Warfarin, DICDIC Vit K defcifiencyVit K defcifiency
Prolonged PTProlonged PT
Mixing studiesMixing studies Corrected mixCorrected mix
Factor assays VIIFactor assays VII Liver function testsLiver function tests Vit KVit K
Non corrected mixNon corrected mix Factor specific inhibitorsFactor specific inhibitors Lupus anticoagulant unlikelyLupus anticoagulant unlikely
Controversy re the role of routine preop Controversy re the role of routine preop screening for U/L bleeding disorderscreening for U/L bleeding disorder
Bolger et al found 6 coagulation disorders in 52 pts Bolger et al found 6 coagulation disorders in 52 pts undergoing preop screening for adenotonsillectomy. undergoing preop screening for adenotonsillectomy. recommended preop screening in all patients recommended preop screening in all patients
In a retrospective review of 994 patients, Manning et al In a retrospective review of 994 patients, Manning et al found that preop PT/PTT failed to identify any patients found that preop PT/PTT failed to identify any patients with occult coagulopathies. with occult coagulopathies.
Burk et al performed a retrospective review of 1603 Burk et al performed a retrospective review of 1603 patients undergoing adenotonsillectomy. Preoperative patients undergoing adenotonsillectomy. Preoperative screening , a careful bleeding history is used to identify screening , a careful bleeding history is used to identify any potential bleeding disorders and guide further any potential bleeding disorders and guide further laboratory disorders.laboratory disorders.
Hutchinson revised a questionnaire originally written by Rappaport. Hutchinson revised a questionnaire originally written by Rappaport. Reviewing these questions with each patient or parent will identify Reviewing these questions with each patient or parent will identify
many bleeding disorders. many bleeding disorders.
Has the patient ever bled for a prolonged period of time after biting Has the patient ever bled for a prolonged period of time after biting the tongue, cheek, or lip? the tongue, cheek, or lip?
Does the patient develop spontaneous bruises larger than 4 to 5 cm Does the patient develop spontaneous bruises larger than 4 to 5 cm in diameter? in diameter?
Has the patient experienced prolonged bleeding following minor Has the patient experienced prolonged bleeding following minor surgical procedures such as circumcision, skin biopsies, or dental surgical procedures such as circumcision, skin biopsies, or dental extractions? Has bleeding recurred 24 hours after the cessation of extractions? Has bleeding recurred 24 hours after the cessation of hemorrhage? hemorrhage?
What medications has the patient been taking during the last 10 What medications has the patient been taking during the last 10 days? Has the patient ingested any antiplatelet agents such as days? Has the patient ingested any antiplatelet agents such as aspirin? aspirin?
Does the patient have any blood relatives with any known bleeding Does the patient have any blood relatives with any known bleeding disorder? Have any other these relatives had prolonged bleeding disorder? Have any other these relatives had prolonged bleeding requiring the use of blood transfusions? requiring the use of blood transfusions?
Does the patient have any systemic medical disorders that might Does the patient have any systemic medical disorders that might result in excessive bleeding (Lupus, liver or renal disease)? result in excessive bleeding (Lupus, liver or renal disease)?
Use of Recombinant factor Use of Recombinant factor VIIa in massive bleedingVIIa in massive bleeding
Novo SevenNovo Seven
Definition Massive Blood LossDefinition Massive Blood Loss
Commonly defined as replacement of patient’s Commonly defined as replacement of patient’s total blood volume or transfusion of >10 units total blood volume or transfusion of >10 units of blood within 24 hoursof blood within 24 hours
eg in a 70kg adult - translates to an estimated eg in a 70kg adult - translates to an estimated replacement of 4-5L of blood lost, or the transfusion of 16-replacement of 4-5L of blood lost, or the transfusion of 16-20 units of packed RBC20 units of packed RBC
2nd definition: replacement of 50% of 2nd definition: replacement of 50% of circulating blood volume in <3hrs or bleeding circulating blood volume in <3hrs or bleeding >150ml/min >150ml/min
(Normal blood volume approximately 7% of (Normal blood volume approximately 7% of ideal body weight in adults)ideal body weight in adults)
70 ml X Kg 70 ml X Kg
Issues in massive transfusion settingsIssues in massive transfusion settings
Haemostatic defectsHaemostatic defects ““Unknown” patientsUnknown” patients Appropriateness of usage - especially of non-red cell Appropriateness of usage - especially of non-red cell
supportsupport Stocks / Inventory managementStocks / Inventory management CommunicationCommunication Rapid performance of investigations & compatibility Rapid performance of investigations & compatibility
teststests Rapid issue of blood productsRapid issue of blood products Haematological advice/consultationHaematological advice/consultation DocumentationDocumentation
Impaired HaemostasisImpaired Haemostasis
Impaired haemostasis is a frequent Impaired haemostasis is a frequent finding in trauma & may be multifactorialfinding in trauma & may be multifactorial dilutional coagulopathydilutional coagulopathy dilutional thrombocytopeniadilutional thrombocytopenia disseminated intravascular disseminated intravascular
coagulationcoagulation hypothermiahypothermia acidosisacidosis platelet dysfunctionplatelet dysfunction volume expandersvolume expanders
Haemostatic effects of colloidsHaemostatic effects of colloids
all semi-synthetic colloid solutions produce some all semi-synthetic colloid solutions produce some impairment of haemostasisimpairment of haemostasis
Primarily due to haemodilution of clotting factorsPrimarily due to haemodilution of clotting factors Gelatins (e.g. Haemaccel & Gelofusin) - least impact Gelatins (e.g. Haemaccel & Gelofusin) - least impact
on haemostasison haemostasis Dextrans - more significant haemostatic Dextrans - more significant haemostatic
derangements - max dose 1.5g/kg to avoid risk derangements - max dose 1.5g/kg to avoid risk bleedingbleeding
lowMW dextrans increase microvascular flow & lowMW dextrans increase microvascular flow & have specific effects - FVIII activity reduced, have specific effects - FVIII activity reduced, plasminogen activation and fibrinolysis increased, plasminogen activation and fibrinolysis increased, clot strength reduced & platelet function impairedclot strength reduced & platelet function impaired
Dilutional CoagulopathyDilutional Coagulopathy
72 kg Adult trauma victim72 kg Adult trauma victim 5 litre whole blood volume5 litre whole blood volume Pre-trauma haematocrit 45%Pre-trauma haematocrit 45% Initial plasma volume 5000 ml x Initial plasma volume 5000 ml x
(100-45) = 2750 ml plasma(100-45) = 2750 ml plasma Haemorrhage of 60% of whole blood Haemorrhage of 60% of whole blood
volumevolume Represents loss of: 5000 x 0.6 x Represents loss of: 5000 x 0.6 x
(100-45) plasma = 1650 ml plasma(100-45) plasma = 1650 ml plasma = 8 units of FFP - but...= 8 units of FFP - but...
Dilutional CoagulopathyDilutional Coagulopathy
On-going lossesOn-going losses Do not always need 100% activity Do not always need 100% activity
of clotting factors for haemostasis of clotting factors for haemostasis - e.g.- e.g. Factor V need only 30%Factor V need only 30% Factor X need only 30%Factor X need only 30% Factor XI need only 20%Factor XI need only 20% Fibrinogen need only 40%Fibrinogen need only 40%
Dilutional ThrombocytopeniaDilutional Thrombocytopenia
thrombocytopenia is the most common haemostatic abnormality during and after massive transfusion
microvascular bleeding eg oozing from mucosa, wounds & puncture sites
platelet count of 50 x 109/L during active bleeding should be sufficient for normal haemostasis provided platelet function intact. count of 50 x 109/L expected when red cell concentrates equivalent to 2 blood volumes transfused. However, marked individual variation.
Pharmacological techniques/agentsPharmacological techniques/agents
Antifibrinolytic agentsAntifibrinolytic agents AprotininAprotinin tranexamic acid tranexamic acid EACA (epsilon-aminocaproic acid)EACA (epsilon-aminocaproic acid)
Desmospressin (DDAVP)Desmospressin (DDAVP) Fibrin sealantsFibrin sealants rVIIa (NovoSeven)rVIIa (NovoSeven)
Ongoing Uncrossmatched Blood Issued ie RCC's
2 units uncrossmatched O Neg used
More Uncrossmatched Blood requested
Contact ! ie Page
Call Haematology Registrar or Consultant
>10 Units in 8 Hrs
Thaw 5-10 Units Cryo & Issue 3 Units AB FFP & 5 Units (1pool )Plts
Ongoing Blood & Blood Products Issued ie RCC's, FFP, Plts & Cryo
Massive Blood Loss/Transfusion EpisodesMassive Blood Loss/Transfusion Episodes
Practice Guidelines for component therapy in Massive Blood Loss
FFPFFP:: if APTT,INR >1.5 x normalif APTT,INR >1.5 x normal 2 or more units of FFP2 or more units of FFP 10 -15 mL/kg10 -15 mL/kg
PlateletsPlatelets:: Platelet count < 50 - 100 x10*9/LPlatelet count < 50 - 100 x10*9/L if platelets < 100 then 1platelet poolif platelets < 100 then 1platelet pool if platelets <50 then 2 platelet poolsif platelets <50 then 2 platelet pools
Cryoprecipitate:Cryoprecipitate: Fibrinogen < 1.0 g/LFibrinogen < 1.0 g/L 10 units cryoprecipate10 units cryoprecipate
Date 16/6/05 CH Comment
Time issued from RMH Blood Bank
0330 0700 1200 1400 1530 1630 1730 1900 0200
RCC
6 4
FFP
5 9
PLATELETS
10 10
CRYO
10 20
INR
1.0 1.6 1.5 1.4 1.3 .0.7 0.7
APTT
29 64 47 47 39 87 40
TCT (TCTP)
FIBRINOGEN
2.8 2.1 2.0 3.2 3.2 3.7 3.8
Hb
128 55 68 Clotted 67 92 96
PLT COUNT
163 170 168 207 181 207
NovoSeven given
Activated PlateletsActivated Platelets
Activated by small amount of thrombin Activated by small amount of thrombin generated by TF-VIIa complexgenerated by TF-VIIa complex
Activation leads to negatively charged Activation leads to negatively charged phospholipids being exposed on platelet surfacephospholipids being exposed on platelet surface
Forms the platform for augmentation of Forms the platform for augmentation of coagulationcoagulation IXa generated binds to platelet surface and IXa generated binds to platelet surface and
with VIIIa forms Xase complexwith VIIIa forms Xase complex Xase complex leads to generation of Xase complex leads to generation of
increased thrombin increased thrombin ““Thrombin Burst”Thrombin Burst”
hFVIIGene
Multiple copiesof hFVII gene
Incorporateinto BHK cells
hFVIIgene
Expression ofrFVII in culture medium
Amplification
rFVIIa production
Only approved Only approved fundedfunded indication in indication in AustraliaAustralia
Control of bleeding and surgery Control of bleeding and surgery prophylaxis in patients with prophylaxis in patients with inhibitors to coagulation factors inhibitors to coagulation factors FVIII or FIXFVIII or FIX
Impaired Haemostasis in Massive Impaired Haemostasis in Massive BleedingBleeding
MultifactorialMultifactorial Dilution of platelets and coagulation factors Dilution of platelets and coagulation factors
following transfusion and volume expandersfollowing transfusion and volume expanders Loss of haemostatic factors Loss of haemostatic factors Consumption in clot formationConsumption in clot formation Disseminated intravascular coagulation (DIC)Disseminated intravascular coagulation (DIC) HypothermiaHypothermia AcidosisAcidosis Platelet dysfunctionPlatelet dysfunction Haemostatic impairment due to semisynthetic Haemostatic impairment due to semisynthetic
colloidscolloids All these lead to impaired thrombin generationAll these lead to impaired thrombin generation
Potential benefit of rFVIIa :Potential benefit of rFVIIa :
Bleeding in :Bleeding in : Coagulopathy associated with Coagulopathy associated with
trauma or surgerytrauma or surgery thrombocytopeniathrombocytopenia platelet-function disordersplatelet-function disorders liver failure/ transplantationliver failure/ transplantation intracerebral haemorrhageintracerebral haemorrhage BMTBMT
ContraindicationsContraindications hypersensitivity to mouse, hypersensitivity to mouse,
hamster or bovine proteinshamster or bovine proteins
Current cost of one dose of NovoSeven:Current cost of one dose of NovoSeven:(as at 1/7/2005)(as at 1/7/2005)
e.g. dose in massive blood loss settinge.g. dose in massive blood loss setting e.g. 70 kg patiente.g. 70 kg patient (round up weight to 72 kg)(round up weight to 72 kg) give 100 give 100 μg per kgμg per kg = 7200 μg = 7.2 mg= 7200 μg = 7.2 mg = 6 vials each of 1.2 mg= 6 vials each of 1.2 mg = 6 x ($1208.26 for each 1.2 mg vial)= 6 x ($1208.26 for each 1.2 mg vial)
= = $7249.56 $7249.56 (without GST)(without GST)
Dose/Presentation/ AdministrationDose/Presentation/ Administration
powder for reconstitution, stored at 2-8Cpowder for reconstitution, stored at 2-8C sterile water for injection for reconstitution sterile water for injection for reconstitution
(2.2mL with 1.2mgvial)(2.2mL with 1.2mgvial) vials 1.2mg, 2.4mg, 4.8mg - usual stock vials 1.2mg, 2.4mg, 4.8mg - usual stock
1.2mg1.2mg dose recommended 100mcg/kg rounded to dose recommended 100mcg/kg rounded to
nearest whole vialnearest whole vial administered as IV bolus over 2-5minutesadministered as IV bolus over 2-5minutes time to peak concentration 15 minutestime to peak concentration 15 minutes elimination half life 2-3 hourelimination half life 2-3 hour
Treatment of traumatic bleedingwith recombinant factor VIIa
Gili Kenet, Raphael Walden, Arieh Eldad, Uri Martinowitz
Surgical intervention failed to stop life-threatening bleeding caused by injury complicated by severe coagulopathy. Administration ofrecombinant factor VIIa immediately corrected the coagulopathy and bleeding stopped.
THE LANCET • Vol 354 • November 27, 1999
Recombinant activated factor VII for Recombinant activated factor VII for adjunctive hemorrhage control in traumaadjunctive hemorrhage control in trauma
Uri Martinowitz et alUri Martinowitz et al J TraumaJ Trauma 51(3) 431-439 2001 51(3) 431-439 2001
7 Massively bleeding trauma pts7 Massively bleeding trauma pts Average of 40 units of blood eachAverage of 40 units of blood each Rx NovoSeven Rx NovoSeven Bleeding almost stopped in all casesBleeding almost stopped in all cases Reduction of APTT/PTReduction of APTT/PT
11stst USA case report of FVIIa in trauma USA case report of FVIIa in trauma
Successful use of recombinant activated factor Successful use of recombinant activated factor VII for trauma-associated hemorrhage in a VII for trauma-associated hemorrhage in a patient without pre-existing coagulopathypatient without pre-existing coagulopathy
Patricia O’Neill et alPatricia O’Neill et al J TraumaJ Trauma 52: 400-405 2002 52: 400-405 2002
24 yo female stabbed 6 times to right chest / 24 yo female stabbed 6 times to right chest / epigastrium / limbsepigastrium / limbs
Aggressive volume expansion / surgery / Aggressive volume expansion / surgery / transfusion supporttransfusion support
Prolonged surgery to hepatic lacerationsProlonged surgery to hepatic lacerations After 108 units of red cells, 78 units FFP, 18 After 108 units of red cells, 78 units FFP, 18
units cryoprecipitate, eqiv 60 units platelets / units cryoprecipitate, eqiv 60 units platelets / further surgery x 2 / gelfoam packing / further surgery x 2 / gelfoam packing / angiographic embolisation – the bleeding angiographic embolisation – the bleeding continuedcontinued
One dose of rFVII given – bleeding ceased One dose of rFVII given – bleeding ceased immediatelyimmediately
Safety profile of recombinant factor VIISafety profile of recombinant factor VII Harold Roberts et alHarold Roberts et al Seminars in HematolSeminars in Hematol 41: 101-108 2004 41: 101-108 2004
10 years of usage in haemophiliacs with 10 years of usage in haemophiliacs with inhibitors & bleedinginhibitors & bleeding
>400,000 doses>400,000 doses Expanding usage in cardiac surgery & Expanding usage in cardiac surgery &
trauma settingtrauma setting No increase in thrombosis rateNo increase in thrombosis rate
No of reported thrombotic events in No of reported thrombotic events in haemophilia patients with inhibitorshaemophilia patients with inhibitors
Total of 1939 treated Total of 1939 treated bleeding episodesbleeding episodes
298 separate patients298 separate patients 0.8% event rate0.8% event rate
CVACVA 22 AMIAMI 77 DICDIC 22 DVTDVT 66
Safety profile of rFVIIaSafety profile of rFVIIa
Requires tissue factor from injured site Requires tissue factor from injured site for activity – thus effect confinedfor activity – thus effect confined
0.2% thrombosis rate in haemophiliac 0.2% thrombosis rate in haemophiliac groupgroup
Fatal thrombosis rate of 4 in 5522 cases Fatal thrombosis rate of 4 in 5522 cases (0.07%)(0.07%)
One thrombotic cerebral infarction in 10 One thrombotic cerebral infarction in 10 patients treated for SAHpatients treated for SAH
AMI 5 pts of 7 > 70 yearsAMI 5 pts of 7 > 70 years 1 AMI occurred 3 days post dose (also on 1 AMI occurred 3 days post dose (also on
tranexamic acid)tranexamic acid) 1 AMI following continuous infusion of FVII for 1 AMI following continuous infusion of FVII for
dental proceduredental procedure
6 Cerebral thrombotic events. 3 patients had pre-6 Cerebral thrombotic events. 3 patients had pre-existing cerebrovascular diseaseexisting cerebrovascular disease
1 occipital infarct following craniotomy1 occipital infarct following craniotomy 1 DVT / PE in Glanzmann’s pt1 DVT / PE in Glanzmann’s pt
NovoSeven / ThrombosisNovoSeven / Thrombosis
Recombinant activated factor VII for the Recombinant activated factor VII for the treatment of life-threatening haemorrhagetreatment of life-threatening haemorrhage
John Eikelboom et al.John Eikelboom et al. Blood Coag Fibrinolysis 14: 713-717 2003Blood Coag Fibrinolysis 14: 713-717 2003
Use national email-out to gather casesUse national email-out to gather cases 21 patients (22-79 years)21 patients (22-79 years) Multi-trauma / cardiac or vascular surgery / liver Multi-trauma / cardiac or vascular surgery / liver
transplantationtransplantation Median pre-Factor VIIa usage of 22 units of red cellsMedian pre-Factor VIIa usage of 22 units of red cells Median INR 1.6 Median APTT 55sMedian INR 1.6 Median APTT 55s In 24 hours post FVIIa median red cells usage was 2 In 24 hours post FVIIa median red cells usage was 2
unitsunits 16/21 alive at 30 days16/21 alive at 30 days No thrombotic complicationsNo thrombotic complications
Royal Perth HospitalRoyal Perth HospitalPatient CharacteristicsPatient Characteristics
• 18 massively transfused, coagulopathic 18 massively transfused, coagulopathic patients (no pre-existing patients (no pre-existing coagulopathy)coagulopathy)
• Median age 44 (range 22-79)Median age 44 (range 22-79)
• Females 5 (28%), Males 13 (72%)Females 5 (28%), Males 13 (72%)
• Cause of bleeding/surgical procedureCause of bleeding/surgical procedure7 cardiac/vascular surgery 7 cardiac/vascular surgery 5 orthoptic liver transplant5 orthoptic liver transplant2 chronic liver disease with coagulopathy2 chronic liver disease with coagulopathy2 multitrauma 2 multitrauma 1 fatty liver of pregnancy, caesarian section1 fatty liver of pregnancy, caesarian section1 severe 1 severe haemorrhagichaemorrhagic pancreatitis pancreatitis
Coagulation Profile before and after rVIIaCoagulation Profile before and after rVIIa
BeforerVIIa*
AfterrVIIa*†
P-value‡
INR 1.6(1.4-3.6) 1.0(0.9-1.2) <0.0001
APTT 54 (31-180) 40 (30-94) 0.0009
Fibrinogen 1.8 (1.2-4.3) 2.6 (1.5-4.6) 0.09
†
*Median, range† First result after rVIIa given‡Paired Wilcoxon signed rank sum test
Transfusion beforeTransfusion before andand 24 hours after rVIIa 24 hours after rVIIa
020
40
60
before after
Pack
ed c
ells
Currently at RMHCurrently at RMH
When NovoSeven is requested / recommendedWhen NovoSeven is requested / recommended Direct consultation with haematology consultant and Direct consultation with haematology consultant and
treating consultant with patienttreating consultant with patient Usually only considered after failure of aggressive Usually only considered after failure of aggressive
non-red cell blood product support to achieve non-red cell blood product support to achieve haemostasishaemostasis
MPH: treating consultant advised to contact health MPH: treating consultant advised to contact health fund/ hospital management to get agreement for fund/ hospital management to get agreement for paymentpayment
Funding issues/ process: to be resolvedFunding issues/ process: to be resolved Increasing frequency of requestsIncreasing frequency of requests
RMH Guidelines for recombinant Factor VIIa Recombinant Factor VIIa may be considered in the following situation (each of these criteria should be met): 1. Massively transfused patients (more than 10 units of red cells in 24 hours or
replacement of blood volume within 3 hours) with ongoing bleeding and coagulopathy
2. Persistent bleeding despite:-
2.1 Appropriate blood component transfusion (fresh-frozen plasma, platelets, cryoprecipitate) to try and correct coagulopathy
2.2 Pharmacologic measures (DDAVP, anti-fibrinolytic agents)
2.3 General haemostatic measures (including efforts to correct hypothermia, hypocalcaemia)
2.4 Surgical intervention where appropriate.
3. The treating Consultant (Surgeon, Anaesthetist, Intensive Care Physician) must consider the condition of the patient to be such that he/she is likely to die of ongoing bleeding. The Unit/Divisional Head must also agree with this decision. This should be documented in the patient medical records.
4. A full blood count and coagulation profile (APTT, INR, and fibrinogen) should be available prior to considering the use of recombinant factor VIIa and should be repeated after the product is administered to assess response
5. The decision to use recombinant Factor VIIa should be made in consultation with the on-call haematologist. Further blood component transfusion (fresh frozen plasma, platelets, cryoprecipitate) may need to be given after recombinant factor VIIa, as appropriate.
If bleeding and coagulopathy continue
after conventional therapy
(usually: 10 units RBC,8 units FFP,
8 units platelets, 10 units cryoprecipitate)
10/8/8/10
rFVIIa100 µg/kg
(rounded to whole vial)
If no response in 20 minutes
Consider 2nd dose of rFVIIa
(100 µg/kg)
Laboratory Tests
Repeat blood tests after each 4-6 units RBCs
PT, APTT > 1.5 X control 4 units FFPFibrinogen < 1g/L 10 units cryoprecipitatePlatelet count < 75 X 109/l 4 units of platelets
Consider calcium chloride
AppropriateMedical interventions
- prevent and reverse hypothermia- prevent and reverse acidosis- correct coagulopathy - heparin reversal - warfarin reversal - consider antifibrinolytic agents
Note:• Use of rFVIIa in children and pregnancy requires special consideration of risk/benefits• Early use may be considered in high-risk groups e.g. patients with cirrhosis and undergoing liver surgery
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Critical Bleeding and Coagulopathy
Recombinant factor VIIa for life threatening post-partum haemorrhageRecombinant factor VIIa for life threatening post-partum haemorrhage
J Ahonen and R Jokela. Recombinant factor VIIa for life threatening post-partum haemorrhageBritish Journal of Anaethesia (2005) 1-4
NovoSeven SummaryNovoSeven Summary
Effective in 90 % of Effective in 90 % of cases (case reports)cases (case reports)
Not derived from Not derived from bloodblood
Not antigenicNot antigenic Effective when other Effective when other
Rx has failedRx has failed Unaffected by blood Unaffected by blood
supply shortagessupply shortages
Currently off-label for Currently off-label for trauma / CT Surgerytrauma / CT Surgery
Incidence of serious Incidence of serious adverse events <1%adverse events <1%
CautionCaution ElderlyElderly Those with pre-existing Those with pre-existing
thrombotic risk factorsthrombotic risk factors Intra-cranial pathology / Intra-cranial pathology /
surgerysurgery DIC / sepsisDIC / sepsis