Newswise — Among patients with oral anticoagulation-associated intracerebral hemorrhage (bleeding within the brain), reversal of international normalized ratio (INR; a measure used to determine the clotting tendency of blood while on medication) below a certain level within 4 hours and systolic blood pressure less than 160 mm Hg at 4 hours were associated with lower rates of hematoma (a localized swelling filled with blood) enlargement, and resumption of anticoagulant therapy was associated with a lower risk of ischemic events without increased bleeding complications, according to a study in the February 24 issue of JAMA.

The prevalence of cardiovascular diseases requiring long-term oral anticoagulation (OAC) is increasing. The most significant complication of OAC is intracerebral hemorrhage (ICH). Among all types of stroke, there is a substantial lack of data about how to manage OAC-ICH. Two of the most pressing unsettled questions are how to prevent hematoma enlargement and how to manage anticoagulation in the long-term. Consensus exists that elevated INR levels should be reversed to minimize hematoma enlargement, yet mode of reversal, timing, and extent of INR reversal are unclear. Valid data on safety and clinical benefit of OAC resumption are missing and remain to be established, according to background information in the article.

Hagen B. Huttner, M.D., of the University of Erlangen-Nuremberg, Erlangen, Germany, and colleagues conducted a study to assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. The study, conducted at 19 German tertiary care centers (2006-2012), included 1,176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption.

Hemorrhage enlargement occurred in 307 of 853 patients (36.0 percent). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8 percent]) vs INR of ≥ 1.3 (264/636 [41.5 percent]) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1 percent]) vs ≥ 160 mm Hg (98/187 [52.4 percent]).The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (18.1 percent vs 44.2 percent not achieving these values) and lower rates of in-hospital death (13.5 percent vs 20.7 percent).

OAC was resumed in 172 of 719 survivors (23.9 percent). OAC resumption showed fewer ischemic complications (5.2 percent vs no OAC, 15.0 percent) and not significantly different hemorrhagic complications (8.1 percent vs no OAC, 6.6 percent).

“The study represents the largest cohort of patients with OAC­ICH to date and reports 2 clinically valuable associations. First, rates of hematoma enlargement were decreased in patients with INR values reversed below 1.3 within 4 hours of admission and systolic blood pressures of less than 160 mm Hg at 4 hours. Second, rates of ischemic events were decreased among patients who restarted OAC without increased rates of bleeding complications,” the authors write.

“These retrospective findings require replication and assessment in prospective studies.”(doi:10.1001/jama.2015.0846; Available pre-embargo to the media at

Editor’s Note: This work was supported by a research grant from the Johannes and Frieda Marohn Foundation, University of Erlangen, Germany. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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