Role of Factor Concentrates in Perioperative Coagulopathies Dr Neville Gibbs Department of Anaesthesia Sir Charles Gairdner Hospital

Role of Factor Concentrates in Role of Factor Concentrates in Perioperative CoagulopathiesPerioperative Coagulopathies

Dr Neville GibbsDr Neville GibbsDepartment of AnaesthesiaDepartment of AnaesthesiaSir Charles Gairdner HospitalSir Charles Gairdner Hospital

Conflicts of InterestConflicts of Interest

NoneNone

Causes of CoagulopathyCauses of Coagulopathy

DiseasesDiseasesDrugsDrugsDilutionDilutionDestructionDestructionDICDIC

Causes of CoagulopathyCauses of Coagulopathy

DiseasesDiseasesDrugsDrugsDilutionDilutionDestructionDestructionDICDICDrop in temperature, pH, calciumDrop in temperature, pH, calcium

Treatment of CoagulopathyTreatment of Coagulopathy

ProtamineProtaminePlasmaPlasmaPlateletsPlateletsPharmacological agentsPharmacological agents


ProtamineProtaminePlasma; Plasma; fractions; fractions; PlateletsPlateletsPharmacological agentsPharmacological agents


ProtamineProtaminePlasma; Plasma; fractions; factor concentratesfractions; factor concentratesPlateletsPlateletsPharmacological agentsPharmacological agents



DDAVPDDAVPTranexamic acidTranexamic acidRecombinant factor VIIaRecombinant factor VIIa




Proline, PatienceProline, Patience




Proline, PatienceProline, Patience

Haemostasis may be possible despite a Haemostasis may be possible despite a severe coagulopathysevere coagulopathy

Bleeding may occur despite normal Bleeding may occur despite normal coagulationcoagulation

Treatment required only for bleeding Treatment required only for bleeding associated with coagulopathyassociated with coagulopathy

Is Treatment Required?Is Treatment Required?

Treatment of coagulopathy is ALWAYS associated with Treatment of coagulopathy is ALWAYS associated with riskrisk

Treatment of coagulopathy is ALWAYS associated with Treatment of coagulopathy is ALWAYS associated with costcost

Treatment of coagulopathy is NOT always associated with Treatment of coagulopathy is NOT always associated with benefit!benefit!

Benefits, Risks, and CostsBenefits, Risks, and Costs

Consensus GuidelinesConsensus Guidelines

Consensus SummaryConsensus Summary

Avoid hypothermia, acidosis, hypocalcemia and Avoid hypothermia, acidosis, hypocalcemia and shockshock

Plasma products to maintain INR <1.5; aPTT Plasma products to maintain INR <1.5; aPTT <45s; fibrinogen >100mg/dL<45s; fibrinogen >100mg/dL

Platelets to maintain platelet count >50,000/mLPlatelets to maintain platelet count >50,000/mLConsider rFVIIa if conventional management Consider rFVIIa if conventional management

has proved ineffectivehas proved ineffective

Tranexamic AcidTranexamic Acid

Consensus GuidelinesConsensus Guidelines

Conventional Plasma ProductsConventional Plasma Products

Fresh Frozen PlasmaFresh Frozen Plasma300mL300mLfactor levels >70% of normalfactor levels >70% of normal

CryoprecipitateCryoprecipitate20mL20mL>70iu FVIII>70iu FVIII>140mg fibrinogen>140mg fibrinogen

Factor ConcentratesFactor Concentrates

Fibrinogen concentrateFibrinogen concentrate

Prothombin complex concentrateProthombin complex concentrate

Recombinant factor VIIaRecombinant factor VIIa

Factor XIII concentrateFactor XIII concentrate

Fibrinogen ConcentrateFibrinogen Concentrate

Highly purified fibrinogen Highly purified fibrinogen concentrate from pooled human concentrate from pooled human plasma; pasteurized for viral plasma; pasteurized for viral inactivationinactivation

Approved in some countries for the Approved in some countries for the treatment of bleeding in patients treatment of bleeding in patients with congenital and certain acquired with congenital and certain acquired fibrinogen deficienciesfibrinogen deficiencies


1 – 2g vials1 – 2g vialsStored at room TStored at room T5 year shelf-life5 year shelf-life



Possible to increase fibrinogen level Possible to increase fibrinogen level >150mg/dL (unlike FFP):>150mg/dL (unlike FFP):



Possible to increase fibrinogen level Possible to increase fibrinogen level >150mg/dL (unlike FFP): improves >150mg/dL (unlike FFP): improves clot firmness;clot firmness;



Possible to increase fibrinogen level Possible to increase fibrinogen level >150mg/dL (unlike FFP): improves >150mg/dL (unlike FFP): improves clot firmness; may reduce bleedingclot firmness; may reduce bleeding

Prothrombin Complex ConcentrateProthrombin Complex Concentrate

Freeze-dried human factors II, IX, X (Freeze-dried human factors II, IX, X (± ± small amounts of VII)small amounts of VII)

Donor screening; viral inactivationDonor screening; viral inactivation


Freeze-dried human factors II, IX, X (Freeze-dried human factors II, IX, X (± ± small amounts of VII)small amounts of VII)

Donor screening; viral inactivationDonor screening; viral inactivation

Indication: Warfarin reversalIndication: Warfarin reversalDose 25-50iu/kgDose 25-50iu/kg


Used for rapid reversal of warfarin Used for rapid reversal of warfarin effecteffect

Advantages Advantages vsvs FFP include low volume FFP include low volume and faster action (<60min and faster action (<60min vsvs 2h); no 2h); no thawing; long shelf-lifethawing; long shelf-life

Disadvantages include increased risk of Disadvantages include increased risk of thrombosis thrombosis (? low protein C, S levels)(? low protein C, S levels)

Should be given with Vit K Should be given with Vit K ((± FFP!)± FFP!)


Need for 4 factor PCC or added FFP?Need for 4 factor PCC or added FFP?


Need for 4 factor PCC or added FFP?Need for 4 factor PCC or added FFP?Factor half-livesFactor half-lives

Factor II: 45-60hFactor II: 45-60hFactor VII: 4-6hFactor VII: 4-6hFactor IX: 14-68hFactor IX: 14-68hFactor X: 24-40hFactor X: 24-40h







If warfarin stopped >6-12h, factor VII If warfarin stopped >6-12h, factor VII may not be necessarymay not be necessary


ContraindicationsContraindications

Allergy to PCCAllergy to PCCActive thrombosisActive thrombosisDICDIC


ContraindicationsContraindications

Allergy to PCCAllergy to PCCActive thrombosisActive thrombosisDICDIC

Patients at high risk of venous or arterial thrombosis Patients at high risk of venous or arterial thrombosis (including MI)(including MI)


Is there a role for prothombin complex Is there a role for prothombin complex concentrates in other perioperative concentrates in other perioperative coagulopathies?coagulopathies?


Is there a role for prothombin complex Is there a role for prothombin complex concentrates in other perioperative concentrates in other perioperative coagulopathies?coagulopathies?

Only with ‘ethics approval’ and ‘informed consent’, Only with ‘ethics approval’ and ‘informed consent’, or if there is no conventional alternativeor if there is no conventional alternative


Is there a role for conventional Is there a role for conventional alternatives (ie. FFP) in the acute alternatives (ie. FFP) in the acute reversal of warfarin? reversal of warfarin?


Is there a role for conventional Is there a role for conventional alternatives (ie. FFP) in the acute alternatives (ie. FFP) in the acute reversal of warfarin? reversal of warfarin?

Only if there are contraindications to Only if there are contraindications to PCCPCC

Recombinant FVIIaRecombinant FVIIaApproved UseApproved Use– Patients with VIIIC deficiency with inhibitors; congenital VII Patients with VIIIC deficiency with inhibitors; congenital VII

deficiency deficiency Off Label UseOff Label Use– Extensive level IV evidence for use as ‘rescue therapy’ in Extensive level IV evidence for use as ‘rescue therapy’ in

trauma and surgerytrauma and surgery– Safety, cost, and consent issuesSafety, cost, and consent issues– ‘‘Justified’ only for life-threatening coagulopathic bleeding, Justified’ only for life-threatening coagulopathic bleeding,

unresponsive to maximal conventional therapyunresponsive to maximal conventional therapy

Recombinant FVIIaRecombinant FVIIa

Experience with RFVIIaExperience with RFVIIaPeak effect within minutesPeak effect within minutesRequires adequate fibrinogen levelsRequires adequate fibrinogen levelsLess effective in hypothermic and acidotic Less effective in hypothermic and acidotic patientspatientsPromotes haemostasis by correcting coagulopathyPromotes haemostasis by correcting coagulopathyIneffective if bleeding is not coagulopathic Ineffective if bleeding is not coagulopathic

Factor XIII ConcentrateFactor XIII Concentrate

Approved for use for FXIII deficiencyApproved for use for FXIII deficiencyHas been shown to increase clot Has been shown to increase clot

firmness firmness in vitroin vitro and and ex vivo (ex vivo (Korte Korte et al. Anesthesiology; 2009;110:239)et al. Anesthesiology; 2009;110:239)

SummarySummary

1. There is a 1. There is a definitedefinite role for role for prothrombin complex concentrate prothrombin complex concentrate for acute reversal of warfarin for acute reversal of warfarin effect; However, PCCs are relatively effect; However, PCCs are relatively contraindicated for most other contraindicated for most other perioperative coagulopathiesperioperative coagulopathies

SummarySummary

2. There is a 2. There is a definitedefinite role for role for recombinant FVIIa as ‘rescue recombinant FVIIa as ‘rescue therapy’ in patients who have therapy’ in patients who have ongoing life-threatening bleeding ongoing life-threatening bleeding andand severe coagulopathy severe coagulopathy despite despite maximal conventional maximal conventional management management

SummarySummary

3. There is a 3. There is a potentialpotential role for role for fibrinogen concentrate to replace fibrinogen concentrate to replace and increase fibrinogen levels in and increase fibrinogen levels in patients with dilutional patients with dilutional coagulopathy; cryoprecipitate is coagulopathy; cryoprecipitate is the conventional alternativethe conventional alternative

SummarySummary

4. There is a 4. There is a theoreticaltheoretical role for role for factor XIII concentrate in patients factor XIII concentrate in patients with a persistent perioperative with a persistent perioperative coagulopathycoagulopathy

SummarySummary

5. There is a 5. There is a theoreticaltheoretical potential for potential for avoiding all conventional plasma avoiding all conventional plasma products in the management of products in the management of perioperative coagulopathy: This is perioperative coagulopathy: This is the direction of current research the direction of current research into coagulation managementinto coagulation management

Documents

Role of Factor Concentrates in Perioperative Coagulopathies Dr Neville Gibbs Department of Anaesthesia Sir Charles Gairdner Hospital