Anticoagulant Reversal Handbook - Page 13


Comparison of FFP and 4F-PCC in warfarin reversal

A comparison of the efficacy and safety of four-factor prothrombin complex concentrate compared with that of plasma in vitamin K antagonist coagulopathy and bleeding is given
Jerrold H Levy MD FAHA FCCM Professor of Anesthesiology ; Associate Professor of Surgery ; CoDirector , Cardiothoracic ICU ; Duke University Medical Center , North Carolina , USA
Multiple oral anticoagulation agents are increasingly administered in clinical practice and include the novel direct oral anticoagulants and vitamin K antagonists ( VKAs ) for prevention and / or treatment of venous thromboembolic disease . 1 Of the VKAs , warfarin is the most commonly used agent for multiple indications . Despite the increasing use of the newer oral agents , warfarin will continue to be used for antithrombotic prophylaxis for mechanical cardiac valves , for patients with ventricular assist devices , and for a host of other prothrombotic issues ( in particular for patients with atrial fibrillation due to valvular heart disease ). As for all anticoagulants , the ability to urgently reverse their effects is an important consideration for patients with acute uncontrolled bleeding , following traumatic injury , or in patients who require emergency surgery or other interventions . 2 4
Despite the belief among clinicians that intravenous vitamin K and fresh frozen plasma ( FFP ) will acutely reverse warfarin or other VKAs for emergency or urgent reversal , this is not the case . As with all allogeneic blood products , the use of FFP / plasma has the potential for side effects and also limitations including availability . Clinicians often refer to FFP when they are actually administering plasma . FFP is the plasma that is
obtained following collection from whole blood , and frozen within eight hours of collection . Plasma that is often transfused is frozen within 24 hours of collection . However , there are only minor differences in factor levels between the two products that are often administered . Furthermore , FFP and plasma are also used interchangeably as terms for therapeutic interventions .
Although administration of vitamin K restores the ability for vitamin K-dependent factors – factor II ( prothrombin ), factor VII , factor IX , and factor X – to be produced effectively , this is not an immediate response or reversal due to the mechanism of action of warfarin to lower circulating factors , and often requires a day or more to correct . FFP / plasma does allow for administration of vitamin K-dependent factors , but in most patients at least two units , and more commonly four units , that comprise approximately 1 – 2 litres of volume are often required to reduce the
International normalised ratio ( INR ). 5 In the patient with heart failure or renal failure , volume challenges of several units is a common cause of transfusionassociated circulatory overload but also potential for transfusion-related acute lung injury ( TRALI ). 6 , 7 In addition , plasma requires cross matching , and time to acquisition . In addition , the inability of plasma to immediately normalise clotting tests including prothrombin time ( PT )/ INR to less than 1.4 – 1.5 is another major limitation . 8 10
Factor concentrates Factor concentrates , specifically fourfactor prothrombin complex concentrates ( 4F-PCCs ) were developed for acute reversal of VKA anticoagulation . 2 Although multiple factor concentrates exist as therapeutic alternatives for allogeneic blood products , 4F-PCC was developed specifically for warfarin reversal , and contains factors II , VII , IX and X , as well as protein C and protein S ,
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