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Role of Factor Concentrates in Perioperative Coagulopathies. Dr Neville Gibbs Department of Anaesthesia Sir Charles Gairdner Hospital. Conflicts of Interest. None. Causes of Coagulopathy. Diseases Drugs Dilution Destruction DIC. Causes of Coagulopathy. Diseases Drugs
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Role of Factor Concentrates in Perioperative Coagulopathies Dr Neville Gibbs Department of Anaesthesia Sir Charles Gairdner Hospital
Causes of Coagulopathy Diseases Drugs Dilution Destruction DIC
Causes of Coagulopathy Diseases Drugs Dilution Destruction DIC Drop in temperature, pH, calcium
Treatment of Coagulopathy Protamine Plasma Platelets Pharmacological agents
Treatment of Coagulopathy Protamine Plasma; fractions; Platelets Pharmacological agents
Treatment of Coagulopathy Protamine Plasma; fractions; factor concentrates Platelets Pharmacological agents
Treatment of Coagulopathy Protamine Plasma; fractions; factor concentrates Platelets Pharmacological agents DDAVP Tranexamic acid Recombinant factor VIIa
Treatment of Coagulopathy Protamine Plasma; fractions; factor concentrates Platelets Pharmacological agents DDAVP Tranexamic acid Recombinant factor VIIa Proline, Patience
Treatment of Coagulopathy Protamine Plasma; fractions; factor concentrates Platelets Pharmacological agents DDAVP Tranexamic acid Recombinant factor VIIa Proline, Patience
Is Treatment Required? Haemostasis may be possible despite a severe coagulopathy Bleeding may occur despite normal coagulation Treatment required only for bleeding associated with coagulopathy
Benefits, Risks, and Costs Treatment of coagulopathy is ALWAYS associated with risk Treatment of coagulopathy is ALWAYS associated with cost Treatment of coagulopathy is NOT always associated with benefit!
Consensus Summary Avoid hypothermia, acidosis, hypocalcemia and shock Plasma products to maintain INR <1.5; aPTT <45s; fibrinogen >100mg/dL Platelets to maintain platelet count >50,000/mL Consider rFVIIa if conventional management has proved ineffective
Conventional Plasma Products Fresh Frozen Plasma 300mL factor levels >70% of normal Cryoprecipitate 20mL >70iu FVIII >140mg fibrinogen
Factor Concentrates Fibrinogen concentrate Prothombin complex concentrate Recombinant factor VIIa Factor XIII concentrate
Fibrinogen Concentrate Highly purified fibrinogen concentrate from pooled human plasma; pasteurized for viral inactivation Approved in some countries for the treatment of bleeding in patients with congenital and certain acquired fibrinogen deficiencies
Fibrinogen Concentrate 1 – 2g vials Stored at room T 5 year shelf-life
Fibrinogen Concentrate 1 – 2g vials Stored at room T 5 year shelf-life Possible to increase fibrinogen level >150mg/dL (unlike FFP):
Fibrinogen Concentrate 1 – 2g vials Stored at room T 5 year shelf-life Possible to increase fibrinogen level >150mg/dL (unlike FFP): improves clot firmness;
Fibrinogen Concentrate 1 – 2g vials Stored at room T 5 year shelf-life Possible to increase fibrinogen level >150mg/dL (unlike FFP): improves clot firmness; may reduce bleeding
Prothrombin Complex Concentrate Freeze-dried human factors II, IX, X (± small amounts of VII) Donor screening; viral inactivation
Prothrombin Complex Concentrate Freeze-dried human factors II, IX, X (± small amounts of VII) Donor screening; viral inactivation Indication: Warfarin reversal Dose 25-50iu/kg
Prothrombin Complex Concentrate Used for rapid reversal of warfarin effect Advantages vs FFP include low volume and faster action (<60min vs 2h); no thawing; long shelf-life Disadvantages include increased risk of thrombosis (? low protein C, S levels) Should be given with Vit K (± FFP!)
Prothrombin Complex Concentrate Need for 4 factor PCC or added FFP?
Prothrombin Complex Concentrate Need for 4 factor PCC or added FFP? Factor half-lives Factor II: 45-60h Factor VII: 4-6h Factor IX: 14-68h Factor X: 24-40h
Prothrombin Complex Concentrate Need for 4 factor PCC or added FFP? Factor half-lives Factor II: 45-60h Factor VII: 4-6h Factor IX: 14-68h Factor X: 24-40h
Prothrombin Complex Concentrate Need for 4 factor PCC or added FFP? Factor half-lives Factor II: 45-60h Factor VII: 4-6h Factor IX: 14-68h Factor X: 24-40h If warfarin stopped >6-12h, factor VII may not be necessary
Prothrombin Complex Concentrate Contraindications Allergy to PCC Active thrombosis DIC
Prothrombin Complex Concentrate Contraindications Allergy to PCC Active thrombosis DIC Patients at high risk of venous or arterial thrombosis (including MI)
Prothrombin Complex Concentrate Is there a role for prothombin complex concentrates in other perioperative coagulopathies?
Prothrombin Complex Concentrate Is there a role for prothombin complex concentrates in other perioperative coagulopathies? Only with ‘ethics approval’ and ‘informed consent’, or if there is no conventional alternative
Prothrombin Complex Concentrate Is there a role for conventional alternatives (ie. FFP) in the acute reversal of warfarin?
Prothrombin Complex Concentrate Is there a role for conventional alternatives (ie. FFP) in the acute reversal of warfarin? Only if there are contraindications to PCC
Recombinant FVIIa Approved Use • Patients with VIIIC deficiency with inhibitors; congenital VII deficiency Off Label Use • Extensive level IV evidence for use as ‘rescue therapy’ in trauma and surgery • Safety, cost, and consent issues • ‘Justified’ only for life-threatening coagulopathic bleeding, unresponsive to maximal conventional therapy
Recombinant FVIIa Experience with RFVIIa Peak effect within minutes Requires adequate fibrinogen levels Less effective in hypothermic and acidotic patients Promotes haemostasis by correcting coagulopathy Ineffective if bleeding is not coagulopathic
Factor XIII Concentrate Approved for use for FXIII deficiency Has been shown to increase clot firmness in vitro and ex vivo (Korte et al. Anesthesiology; 2009;110:239)
Summary 1. There is a definite role for prothrombin complex concentrate for acute reversal of warfarin effect; However, PCCs are relatively contraindicated for most other perioperative coagulopathies
Summary 2. There is a definite role for recombinant FVIIa as ‘rescue therapy’ in patients who have ongoing life-threatening bleeding and severe coagulopathy despite maximal conventional management
Summary 3. There is a potential role for fibrinogen concentrate to replace and increase fibrinogen levels in patients with dilutional coagulopathy; cryoprecipitate is the conventional alternative
Summary 4. There is a theoretical role for factor XIII concentrate in patients with a persistent perioperative coagulopathy
Summary 5. There is a theoretical potential for avoiding all conventional plasma products in the management of perioperative coagulopathy: This is the direction of current research into coagulation management