Reversibility of Apixaban Anticoagulation with a Four‐Factor Prothrombin Complex Concentrate in Healthy Volunteers

It was hypothesized that the four‐factor prothrombin complex concentrate (4F‐PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two‐period crossover, assessor‐blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four‐factor prothrombin complex concentrate (4F‐PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP‐reagent and PPP‐reagent low, anti‐Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F‐PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F‐PCC and saline in anti‐Xa assessment at 30 min or later time points.