Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding

Abstract

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH). This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine(®) SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded. The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2-3.3) and post-treatment INR was 1.4 (IQR 1.3-1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50-140) min. No patient's INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC. A 3-factor PCC preparation (Profilnine(®) SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.