Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage Despite Anticoagulation Reversal

Abstract

on behalf of the Canadian PCC Registry (CanPro) Investigators* Background and Purpose-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. Methods-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. Results-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 (Ͻ1.5) 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. Conclusions-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. (Stroke. 2012;43:1812-1817.)

Acute subdural hematoma in patients on oral anticoagulant therapy: management and outcome

“…Previously, Senft et al 25 and Taussky et al 30 analyzed a small cohort of patients with aSDH that occurred during OAT (11 and 16 patients) and showed no significant difference in functional outcome or mortality rate. In contrast, several previous studies observing anticoagulation in intracranial hemorrhage reported anticoagulation or antiplatelet treatment at the time of presentation as an important poor prognostic marker, 10,21,24,27,31 and one of the studies 20 reported a 1.7 times higher risk of mortality in patients on OAT at the time of the intracranial hemorrhage. In our study with a larger cohort of patients on OAT (n = 74), we observed similar results, with a clear significance toward unfavorable outcome and a mortality rate in the OAT group that was almost twice as high as that in the no-OAT group.…”

“…25,30 Although most of the experimental as well as clinical studies have shown the prognostic relevance of OAT in intracranial hemorrhage, the relationship between aSDH and OAT remains unclear. 10,13,30,35 In patients receiving OAT who suffer intracranial hemorrhage, first-line management is the reversal of anticoagulation, and the treatment differs depending on the OAT profile. The effectiveness of desmopressin and thrombocyte concentrate in patients treated with antiplatelet agents or prothrombin complex concentrates (PCC) in patients treated with a vitamin K antagonist has been reported in several studies and has recently been addressed in 2 systematic reviews.…”

Effect of Patient Characteristics, Knowledge and Satisfaction with Warfarin Therapy on Willingness to Switch to a New Oral Anticoagulant

“…In addition to these disadvantages, warfarin carries the risk of intracranial hemorrhage which occurs in 0.4% of patients per year and has a mortality of approximately 50% [5][6][7]. Overall these disadvantages have resulted in apprehension in physicians' prescribing and patients' uptake of this medication.…”

“…While it has proven efficacy in treating and preventing thrombotic conditions (stroke and venous thromboembolism [VTE]), warfarin is also associated with several disadvantages such as frequent lab monitoring, multiple drug interactions, narrow therapeutic index and interpersonal variability in metabolism and target effect due to genetic polymorphisms [1][2][3][4][5][6][7]. These factors correlate to a 40-fold This article is available from: http://www.hsprj.com/archive.php…”

Reversing targeted oral anticoagulants

“…Recent data from large cohorts of patients on VKA estimate the fatality rate of VKA-related major bleeding at ϳ15%-20%, up to 50% for intracranial bleeding. 22,23 Although there was no direct comparison with patients treated with VKA, it appears that rates of rivaroxaban-related major bleeding may be lower and outcomes are not worse than in VKA-treated patients. In summary, only small numbers of patients with rivaroxaban-associated bleeding required a reversal strategy, with prohemostatic therapy being given only in life-threatening situations.…”