4-Factor Prothrombin Complex Concentrate Superior to 3-Factor Version for Reversal of Coumarin Anticoagulation in Rat Model

In an established preclinical bleeding model, reversal of coumarin anticoagulation with Kcentra, a four-factor prothrombin complex concentrate (4F-PCC), was shown to be superior to three-factor prothrombin complex concentrates (3F-PCCs), according to findings reported by CSL Behring investigators. Treatment with 4F-PCC was able to fully reverse bleeding, achieving an average bleeding time of 676 seconds. Prior to 4F-PCC therapy, animals had been anticoagulated with coumarin to induce an increase in median bleeding time from an average of 823 seconds to 1,800 seconds; in parallel, prothrombin time (PT) was prolonged from 8.9 seconds to 29.9 seconds prior to treatment.

In addition to normalizing bleeding time, 4F-PCC treatment reversed elevated PT, bringing it down to 15.1 seconds. In contrast, two commercialized 3-PCCs were not able, or were only partially able, to reduce coumarin-induced bleeding; average post-treatment bleeding times were 1,398 and 1,708 seconds. This also corresponded with inferior reductions in PT, with minimum levels of 23.8 and 29.5 seconds.

The investigators concluded that the replenishment of all vitamin K-dependent coagulation factors (factors II, VII, IX and X), including factor VII found in 4F-PCC, may result in superior efficacy compared with the use of 3F-PCC for reversal of coumarin anticoagulation.