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)

Recombinant Factor VIIa (NovoSeven)

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

The LancetVol 354July 10, 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