Incidence of thromboembolic events following administration of four-factor prothrombin complex concentrate (4F-PCC) for oral anticoagulation reversal

Abstract

IntroductionProthrombin complex concentrates (4F-PCC) for anticoagulation reversal pose a risk of thromboembolism although data are limited. This study aims to quantify thromboembolic events (TE) and describe associations. Materials and methodsRetrospective, two-center, study of patients receiving 4F-PCC between September 2013 and December 2017 for warfarin or direct oral anticoagulant (DOAC) reversal. Primary outcome was in-hospital TE incidence and secondary outcomes were to describe characteristics associated with TE. Data are reported descriptively and analyzed with bivariate and multivariate analyses. Results542 patients were included (mean age 73 ± 14 years, 58% male, 76.6% warfarin/23.4% DOAC reversal). Most had intracranial hemorrhage (68.5%) or were undergoing an emergent procedure (13.4%). Fifty patients (9.2%) experienced in-hospital TE and most (62%) occurred within 7 days of 4F-PCC. Younger age (66 vs. 74 years, p < 0.01), presence of a hypercoagulable risk factor (46% vs. 26%, p < 0.01), indication for anticoagulation (p = 0.008), higher 4F-PCC dose (2148 vs. 2000 units, p < 0.01), and longer hospital length of stay (LOS) (21.5 vs. 7 days, p < 0.01) were associated with TE following bivariate analysis. Multivariate analysis identified anticoagulation indication of venous thromboembolism or “other” (e.g., antiphospholipid syndrome, Factor V Leiden) were independently associated with higher incidence of TE compared to receiving anticoagulation for atrial arrhythmia (p = 0.05). Hospital LOS ≥ 7 days was associated with threefold greater odds of TE compared to <7 days (p = 0.003). ConclusionsIn-hospital TE following 4F-PCC was 9.2%, most events occurred within 7 days, and younger age, indication for anticoagulation, and LOS were independently associated with TE which may influence treatment selection.