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Original Investigation |

Early Clinical and Radiological Course, Management, and Outcome of Intracerebral Hemorrhage Related to New Oral Anticoagulants

Jan C. Purrucker, MD1; Kirsten Haas, MPH, PhD2; Timolaos Rizos, MD1; Shujah Khan1; Marcel Wolf, MD3; Michael G. Hennerici, MD4; Sven Poli, MD, MSc5; Christoph Kleinschnitz, MD6; Thorsten Steiner, MD, MME1,7; Peter U. Heuschmann, MD, MPH2,8; Roland Veltkamp, MD1,9
[+] Author Affiliations
1Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
2Institute of Clinical Epidemiology and Biometry, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany
3Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
4Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany
5Department of Neurology and Stroke, Tübingen University, Tübingen, Germany
6Department of Neurology, University Hospital Würzburg, Würzburg, Germany
7Department of Neurology, Frankfurt Hoechst Hospital, Frankfurt am Main, Germany
8Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany
9Department of Stroke Medicine, Imperial College London, London, England
JAMA Neurol. 2016;73(2):169-177. doi:10.1001/jamaneurol.2015.3682.
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Importance  Intracerebral hemorrhage (ICH) is the most devastating adverse event in patients receiving oral anticoagulation. There is only sparse evidence regarding ICH related to the use of non–vitamin K antagonist oral anticoagulant (NOAC) agents.

Objective  To evaluate the early clinical and radiological course, acute management, and outcome of ICH related to NOAC use.

Design, Setting, and Participants  Prospective investigator-initiated, multicenter observational study. All diagnostic and treatment decisions, including administration of hemostatic factors (eg, prothrombin complex concentrate), were left to the discretion of the treating physicians. The setting was 38 stroke units across Germany (February 1, 2012, to December 31, 2014). The study included 61 consecutive patients with nontraumatic NOAC-associated ICH, of whom 45 (74%) qualified for the hematoma expansion analysis.

Main Outcomes and Measures  Hematoma expansion, intraventricular hemorrhage, and reversal of anticoagulation during the acute phase. Recorded were the 3-month functional outcome, factors associated with an unfavorable outcome (modified Rankin Scale score, 3-6), any new intraventricular extension or an increase in the modified Graeb score by at least 2 points, and the frequency of substantial hematoma expansion (defined as relative [≥33%] or absolute [≥6-mL] volume increase).

Results  In total, 41% (25 of 61) of patients with NOAC-associated ICH were female, and the mean (SD) patient age was 76.1 (11.6) years. At admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range, 4-18). The mean (SD) baseline hematoma volume was 23.7 (31.3) mL. In patients with sequential imaging for the hematoma expansion analysis, substantial hematoma expansion occurred in 38% (17 of 45). New or increased intraventricular hemorrhage was observed in 18% (8 of 45). Overall mortality was 28% (17 of 60 [follow-up data were missing in 1 patient]) at 3 months, and 65% (28 of 43) of survivors had an unfavorable outcome (modified Rankin Scale score, 3-6). Overall, 57% (35 of 61) of the patients received prothrombin complex concentrate, with no statistically significant effect on the frequency of substantial hematoma expansion (43% [12 of 28] for prothrombin complex concentrate vs 29% [5 of 17] for no prothrombin complex concentrate, P = .53), or on the occurrence of an unfavorable outcome (modified Rankin Scale score, 3-6) (odds ratio, 1.20; 95% CI, 0.37-3.87; P = .76).

Conclusions and Relevance  Non–vitamin K antagonist oral anticoagulant–associated ICH has a high mortality and an unfavorable outcome, and hematoma expansion is frequent. Larger-scale prospective studies are needed to determine whether the early administration of specific antidotes can improve the poor prognosis of NOAC-associated ICH.

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Functional Outcome in Patients With Intracerebral Hemorrhage Associated With Non–Vitamin K Antagonist Oral Anticoagulant Use

The modified Rankin Scale (mRS) score was recorded before the intracerebral hemorrhage and 90 days after the stroke (0 indicates no symptoms, and 6 indicates death). Before intracerebral hemorrhage, functional status was missing in 2 patients. Outcome at day 90 was missing in 1 patient.

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