Reversal strategies and outcomes in patients with atrial fibrillation and warfarin-associated intracranial hemorrhage

Purpose: Evaluate reversal strategies in atrial fibrillation (AF) patients with warfarin-associated intracranial hemorrhage (ICH) in clinical care. Materials and Methods: Observational cohort of AF patients with warfarin-associated ICH at two referral hospitals (2007-2010), with patient features, reversal agents, and outcomes collected from medical records. Results: Among 498 ICH patients 403 received fresh frozen plasma (FFP) without 3-factor prothrombin complex concentrates (PCCs) or recombinant factor VIIa (rFVIIa), 65 received PCCs or rFVIIa, mostly with FFP, and 30 received no acute reversal agents. Median time from presentation to reversal agent administration was 3.4 h (IQR 2.3-5.3). INR was reversed to <= 1.4 by 6 h post-presentation in 46% of patients receiving PCCs/rFVIIa versus 15% receiving FFP alone (p<0.0001). Among PCCs/rFVIIa recipients, 31% died in-hospital vs. 24% receiving FFP alone (p=0.27). Adjusted OR for death accounting for age and Glasgow Coma Score was 0.78 (0.36-1.69) for PCCs/rFVIIa vs FFP only and 1.16 (0.59-2.27) comparing those reaching vs. not reaching INR <= 1.4 at 6 h. Conclusions: Treatment with PCCs/rFVIIa led to faster INR reversal than treatment with FFP alone. Neither treatment with PCCs/rFVIIa nor rapid INR reversal was associated with improved survival. Delays receiving PCCs may largely eliminate the benefit of treatment.