Fixed-dose Activated Versus Variable-dose Inactivated Prothrombin Complex Concentrate for Warfarin-associated Major Bleed
Fixed-dose Activated Versus Variable-dose Inactivated Prothrombin Complex Concentrate for Warfarin-associated Major Bleed
This study aims to assess a fixed-dose regimen of activated prothrombin complex concentrate
 (FEIBA VH, Baxter) versus the variable, manufacturer recommended, dose regimen of inactivated
 prothrombin complex concentrate (Kcentra, CSL Behring) for reversal of warfarin-associated
 major hemorrhage.
Warfarin, a vitamin K antagonist (VKA), is the most frequently prescribed oral anticoagulant.
 Warfarin-associated major hemorrhage occurs at a rate of 1.7% to 3.4% in routine clinical
 practice and warrants rapid reversal of anticoagulation by correcting supratherapeutic
 international normalized ratio (INR) values.

 Warfarin inhibits synthesis of vitamin K dependent coagulation factors II, VII, IX, and X,
 and strategies for reversal of warfarin-associated coagulopathy are aimed at restoring
 deficient factors. Four-factor prothrombin complex concentrates (PCCs) contain the
 coagulation factors which warfarin inhibits and are an attractive option for rapid reversal
 due to ease of reconstitution and no requirement for blood-type matching.

 Manufacturer dosing recommendations exist for PCCs based on patient weight, baseline INR, and
 target INR, but studies have suggested fixed dosing strategies in an effort to determine the
 most efficacious dose for VKA-reversal while sparing adverse events. These studies have also
 utilized different PCC formulations, with some studies utilizing 4-factor activated PCC
 (aPCC), which denotes product containment of factor VII in an activated state.

 In the United States, product availability is limited to a single 4-factor aPCC (FEIBA VH,
 Baxter) indicated for hemophilia patients with inhibitors and a single 4-factor inactivated
 PCC (Kcentra, CSL Behring) approved for VKA-reversal. Various institutions choose to utilize
 off-label fixed dosing strategies of 4-factor aPCC in an effort to administer the lowest
 possible dose to reverse VKAs, while others utilize manufacturer recommended dosing of
 4-factor inactivated PCC.
Inclusion Criteria:

 -  Pre-treatment INR lab value greater than 1.5

 -  Receipt of treatment with a 4-factor PCC for INR normalization due to
 warfarin-associated major hemorrhage

 Exclusion Criteria:

 -  Patients treated with a PCC for an urgent invasive procedure without active hemorrhage

 -  Patients treated with PCC not taking a VKA

 -  Unavailable pre- or post-treatment INR lab values

 -  Pregnant patients