Role of prothrombin complex concentrates in reversing warfarin anticoagulation: A review of the literature

Abstract

Over-anticoagulation is a common problem with warfarin therapy and can lead to major or life-threatening bleeding. The goal of urgent warfarin reversal is to elevate or replace vitamin K-dependent clotting factors. In the United States, fresh frozen plasma (FFP) is considered the standard of care for warfarin reversal. Prothrombin complex concentrates (PCCs) offer an alternative to FFP for rapidly replacing deficient clotting factors and correcting the international normalized ratio (INR). However, few prospective clinical trials have been conducted to evaluate the effectiveness of these concentrates relative to other treatment modalities. A review of the published literature over the last 30 years found that PCCs offer a rapid and specific method for replacing vitamin K-dependent clotting factors and restoring normal hemostasis in the context of overcoagulation. In those studies in which PCCs were compared with FFP, PCCs were found more effective in shortening the time to INR correction and were associated with a low risk of thrombotic adverse events. Evidence-based treatment guidelines are needed to optimize the use of PCCs for warfarin reversal. Am. J. Hematol. 83:137-143, 2008. V

Warfarin‐related intracerebral haemorrhage: better outcomes when reversal includes prothrombin complex concentrates

“…14 This risk appears to be low, 25,34 possibly between 0% and 5%. 35 The risks of thrombosis particularly associated with the original indication for anticoagulation, such as atrial fibrillation or prosthetic heart valves, need to be balanced against the extremely high mortality associated with WRICH of up to 68%.…”

An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies

“…Based on studies showing that PCC reverses VKA therapy more rapidly and more completely than a standard dose of FFP, 1 several expert consensus panels have recommended the use of PCC. [2][3][4] Unfortunately, an optimal dosing strategy for PCC has not been established, and whether or not a low fixed dose can be applied is still under discussion.…”

Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants

“…Moreover, FFP can require substantial time to obtain from the local blood bank and to warm, and full anticoagulation reversal may not be realized until several hours after administration. 29,30 In addition, the total dose of FFP needed to reverse VKA anticoagulation is quite large. Up to 2 L or 10 U are frequently required to increase the level of coagulation proteins in the circulatory system by 0.4 to 0.5 U/mL.…”

“…Prothrombin Table 3 lists the available PCCs and the factor levels in each. 29,38 Activated PCCs (aPCCs) are nanofiltered, vapor-heated, freeze-dried sterile human plasma fractions. The aPCCs have a role as hemostatic agents in VKA reversal in patients with clinically significant bleeding events.…”