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Comparison of Traumatic Intracranial Hemorrhage Expansion and Outcomes Among Patients on Direct Oral Anticoagulants Versus Vitamin k Antagonists



With increasing use of direct oral anticoagulants (DOACs) and availability of new reversal agents, the risk of traumatic intracranial hemorrhage (tICH) requires better understanding. We compared hemorrhage expansion rates, mortality, and morbidity following tICH in patients treated with vitamin k antagonists (VKA: warfarin) and DOACs (apixaban, rivaroxaban, dabigatran).


Retrospective chart review of patients from 2010 to 2017 was performed to identify patients with imaging diagnosis of acute traumatic intraparenchymal, subdural, subarachnoid, and epidural hemorrhage with preadmission use of DOACs or VKAs. We identified 39 patients on DOACs and 97 patients on VKAs. Demographic information, comorbidities, hemorrhage size, and expansion over time, as well as discharge disposition and Glasgow Outcome Scale (GOS) were collected. Primary outcome was development of new or enlargement of tICH within the first 48 h of initial CT imaging.


Of 136 patients with mean (SD) age 78.7 (13.2) years, most common tICH subtype was subdural hematoma (N = 102/136; 75%), and most common mechanism was a fall (N = 130/136; 95.6%). Majority of patients in the DOAC group did not receive reversal agents (66.7%). Hemorrhage expansion or new hemorrhage occurred in 11.1% in DOAC group vs. 14.6% in VKA group (p = 0.77) at a median of 8 and 11 h from initial ED admission, respectively (p = 0.82). Patients in the DOAC group compared to VKA group had higher median discharge GOS (4 vs. 3 respectively, p = 0.03), higher percentage of patients with good outcome (GOS 4–5, 66.7% vs. 40.2% respectively, p = 0.005), and higher rate of discharge to home or rehabilitation (p = 0.04).


We report anticoagulation-associated tICH outcomes predominantly due to fall-related subdural hematomas. Patients on DOACs had lower tICH expansion rates although not statistically significantly different from VKA-treated patients. DOAC-treated patients had favorable outcomes versus VKA group following tICH despite low use of reversal strategies. DOAC use may be a safer alternative to VKA in patients at risk of traumatic brain hemorrhage.

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Dr. Hanley was awarded significant research support through grant numbers 5U01NS062851 for Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage III and for Minimally Invasive Surgery Plus r-tPA for Intracerebral Hemorrhage Evacuation (MISTIE) III 1U01NS080824. Dr. Ziai is supported by grants 5U01NS062851 and 1U01NS080824. Dr. Ziai reports personal fees from CR Bard, Inc. and Portola Pharmaceuticals, outside the submitted work.

Author information

Each of the authors contributed uniquely to the preparation of this manuscript: SS was involved in imaging analysis, data collection, and manuscript preparation; EBM helped in editing and data interpretation; HA contributed to imaging analysis; PAN helped in editing and data interpretation; DFH and MD contributed to editing and data interpretation; WZ was involved in studying concept, statistical analysis, and data interpretation, and he is a senior author.

Correspondence to Wendy C. Ziai.

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Conflict of interest

Dr. Marsh reports sponsored research from the American Heart Association. Dr. Hanley reports sponsored research support from the NIH, and has consulted for BrainScope, Neurotrope, Portola, and Op2Lysis. Dr. Ziai reports sponsored research support from the NIH and has consulted for Bard, Inc. and Portola Pharmaceuticals.

Ethical Approval/Informed Consent

This retrospective study was approved by Johns Hopkins Institutional Review Board. As it was a retrospective data collection, no direct consent was obtained from individual patients.

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Shin, S.S., Marsh, E.B., Ali, H. et al. Comparison of Traumatic Intracranial Hemorrhage Expansion and Outcomes Among Patients on Direct Oral Anticoagulants Versus Vitamin k Antagonists. Neurocrit Care (2020).

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  • Traumatic brain injury
  • TBI
  • Direct oral anticoagulant
  • Novel oral anticoagulant
  • Rivaroxaban
  • Apixaban
  • Dabigatran
  • Intracerebral hemorrhage