Warfarin use leads to larger intracerebral hematomas

Abstract

Background Among patients with intracerebral hemorrhage (ICH) warfarin use prior to onset leads to greater mortality. In a retrospective study we sought to determine if warfarin use is associated with larger initial hematoma volume, one determinant of mortality after ICH. Methods We identified all patients hospitalized with ICH in the Greater Cincinnati region from 1/05–12/05. ICH volumes were measured on the first available brain scan using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine whether international normalized ratio (INR) influenced initial ICH volume after adjusting for other factors including age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Results There were 258 patients with ICH including 51 patients taking warfarin. In univariable comparison, when INR was stratified there was a trend toward a difference in hematoma volume by INR category (INR < 1.2 = 13.4 cc, INR 1.2–2.0 = 9.3 cc, INR 2.1–3.0 = 14.0 cc, INR > 3.0 = 33.2 cc, p = 0.10). In the model, compared to patients with INR < 1.2, there was no difference in hematoma size for patients with INR 1.2–2.0 (p=0.25) or INR 2.1–3.0 (p=0.36), but patients with INR > 3.0 had greater hematoma volume (p=0.02). Other predictors of larger hematoma size were ICH location (lobar compared to deep cerebral, p=0.02) and shorter time from stroke onset to scan (p<0.001). Conclusion Warfarin use was associated with larger initial ICH volume, but this effect was only observed for INR values >3.0. Larger ICH volume among warfarin users likely accounts for part of the excess mortality in this group.

Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events

“…21 When warfarin-related intracerebral hemorrhage occurs, stroke mortality rate doubles in a dose-dependent manner, 22 likely related to the large size of hematoma. 23 Thus, preventing hemorrhagic cerebrovascular events is of paramount importance for those patients who require anticoagulation because of high risk of recurrent embolic stroke. In this analysis, patients with previous IS/TIA randomized to HDER experienced similar protection from arterial thromboembolism and death when compared with well-managed warfarin (median time-in-therapeutic range 68.4%) and superior protection from primary hemorrhagic stroke and ICH, similar to the overall ENGAGE AF-TIMI 48 cohort.…”

Therapeutic Strategies in Acute Intracerebral Hemorrhage

“…The apolipoprotein E ε2 allele is associated with larger hematomas, which appears to explain its effect on outcome [15]. The relation between oral anticoagulation use and baseline hematoma volume is unclear; some studies have shown increased baseline volumes [16,17], whereas others have not [15,18].…”

“…The observed increase is most likely due to the increased use of warfarin by patients with atrial fibrillation [58]. The use of warfarin at the time of ICH is associated with hematoma expansion [16,18] and increased mortality [15][16][17]59].…”

Treatment Targets in Intracerebral Hemorrhage

“…Individuals on warfarin with an international normalized ratio >3 have an increased risk for having larger hematomas [146]. To be able to potentially curtail the hematoma growth of different agents, including vitamin K (either with or without fresh frozen plasma), factor VII, and prothrombin complex concentrates have been used.…”