Coagulation factor plasma levels following administration of a 4-factor prothrombin complex concentrate for rapid vitamin K antagonist reversal in Japanese patients

Publication date: Available online 25 August 2018Source: Current Therapeutic ResearchAuthor(s): Masahiro Yasaka, Andres Brainsky, Peijin Zhang, Shigeki KushimotoAbstractPurposeFour-factor prothrombin complex concentrates (4F-PCCs) have been approved for urgent vitamin K antagonist (VKA) reversal in Western countries for many years. Ethnicity and genetic variations between populations may influence the pharmacokinetic profile of treatments and here we report plasma levels of vitamin K-dependent coagulation factors and proteins C and S in Japanese patients following administration of a 4F-PCC approved recently in Japan.MethodsThis was a subanalysis of a prospective, open-label, phase 3b study in Japanese patients requiring rapid VKA reversal owing to major bleeding (n=6) or need for urgent surgery (n=5). International normalized ratio (INR) and plasma levels of factors II, VII, IX and X, and proteins C and S were measured before PCC infusion and at specific time points for the next 24 hours. Adverse events (AEs) and serious AEs were recorded up to Day 14 and 45, respectively.FindingsRapid increases in plasma concentrations 30 minutes following 4F-PCC infusion were seen for all factors and proteins C and S, with median concentrations compared with baseline increasing by ≥100% and 70% in the bleeding and surgical groups, respectively. A concurrent decrease in INR was observed. Plasma levels for each factor and protein remained within physiological levels throughout the assessme...
Source: Current Therapeutic Research - Category: Drugs & Pharmacology Source Type: research