Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage Despite Anticoagulation Reversal

Abstract

Anticoagulant-associated intracranial hemorrhage (aaICH) presents with larger hematoma volumes, higher risk of hematoma expansion, and worse outcome than spontaneous intracranial hemorrhage. Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of anticoagulation after aaICH. Given the lack of randomized controlled trial evidence of efficacy, and the potential for thrombotic complications, we aimed to determine outcomes in patients with aaICH treated with PCC. We conducted a prospective multicenter registry of patients treated with PCC for aaICH in Canada. Patients were identified by local blood banks after the release of PCC. A chart review abstracted clinical, imaging, and laboratory data, including thrombotic events after therapy. Hematoma volumes were measured on brain CT scans and primary outcomes were modified Rankin Scale at discharge and in-hospital mortality. Between 2008 and 2010, 141 patients received PCC for aaICH (71 intraparenchymal hemorrhages). The median age was 78 years (interquartile range, 14), 59.6% were male, and median Glasgow Coma Scale was 14. Median international normalized ratio was 2.6 (interquartile range, 2.0) and median parenchymal hematoma volume was 15.8 mL (interquartile range, 31.8). Median post-PCC therapy international normalized ratio was 1.4: 79.5% of patients had international normalized ratio correction (<1.5) within 1 hour of PCC therapy. Patients with intraparenchymal hemorrhage had an in-hospital mortality rate of 42.3% with median modified Rankin Scale of 5. Significant hematoma expansion occurred in 45.5%. There were 3 confirmed thrombotic complications within 7 days of PCC therapy. PCC therapy rapidly corrected international normalized ratio in the majority of patients, yet mortality and morbidity rates remained high. Rapid international normalized ratio correction alone may not be sufficient to alter prognosis after aaICH.