From Jane Bossart: Any thoughts on whether Kcentra® (Behring CSL) will be better than Profilnine® (Grifols)? It seems there have been no head to head comparison yet.
Hello, Jane, and thank you for your question. Although non-activated prothrombin complex concentrates (PCCs) and sometimes recombinant activated factor VII have been used off-label in conjunction with vitamin K to rapidly reverse the bleeding associated with Coumadin overdose, Kcentra, known outside the US as Beriplex®, is the first to be FDA-cleared for this indication. Beriplex and Octaplex® (Octapharma) are cleared by the European Medicines Agency (EMA) and Canada Health for Coumadin reversal, and both offer advantages over frozen plasma: no need to match ABO group, no delay during thawing, and no risk of transfusion-associated circulatory overload (TACO). Kcentra and Octaplex are “four-factor” PCCs, providing physiologically active levels of factors II, VII, IX, and X, and additionally, control proteins C and S.
Profilnine® is FDA-cleared only for treatment of factor IX deficiency. It lacks physiologically active levels of factor VII, and is called a “three-factor” PCC, thus may be less effective at Coumadin reversal. See Rossetto V, Sartori MT, Gavasso S, et al. Comparison of three different prothrombin complex concentrates efficacy in reversal of anti-vitamin K effect in patients under oral anticoagulant treatment: an in vitro study. J Thromb Haemostas 2013;11: abstract AS 33.1. The Rosseto study results are equivocal, however, and another study reported in the same journal issue, Levi M, Moore T, Castillejos CF, et al. Effects of three-factor and four-factor prothrombin complex concentrates on the pharmacodynamics of rivaroxaban. J Thromb Haemostas 2013;11: abstract OC 36.5, which is an in vivo study involving normal healthy subjects, indicates that both PCCs may be effective in reversing the lab effects of rivaroxaban overdose. Neither study addresses bleeding, however. Both use shortening of the prothrombin time, reduction of international normalized ratio (INR) to <1.5, and endogenous thrombin potential as surrogate end points, so, as you point out, we need some good clinical outcomes studies for Coumadin and for new oral anticoagulant reversal by the PCCs. Geo.