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Oral anticoagulant-associated intracerebral hemorrhage

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Abstract

The incidence of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) is growing due to the increasing use of warfarin and the older age of treated patients. Recent population studies reveal that OAC-ICH currently occurs at a frequency comparable to that of subarachnoid hemorrhage. Most frequently, OAC-ICH are located in deep or lobar regions of the brain, although it may also occur in the brainstem. These hemorrhages are larger than spontaneous hematomas and may be fatal in at least 50% of cases. The primary cause of brain injury in patients with OAC-ICH is the direct mechanical disruption of the brain tissue but secondary damage may occur through the intervention of matrix metalloproteinases, glutamate, cytokines, heme, iron, and the chemical toxicity of products such as thrombin, which are released from the clot. The pathogenesis of OAC-ICH also includes the effects of aging, the level of anticoagulation, genetic factors, and a high prevalence of concurrent cerebrovascular conditions, such as cerebral amyloid angiopathy, leukoaraiosis or previous strokes. The treatment of OAC-ICH is challenging and involves rapid reversal of anticoagulation with hemostatic drug therapies such as vitamin K, fresh frozen plasma, prothrombin complex concentrates or recombinant factor VIIa. These therapies may not always be sufficient to stabilize the patient’s clinical condition and lacking randomized controlled trials, the best hematological approach to reverse oral anticoagulation is debated. Other difficult decisions reviewed in this article are whether anticoagulation should be restarted after OAC-ICH, and when anticoagulant treatment should be resumed. The newer oral anticoagulants, which are increasingly being introduced for thromboembolism prevention, may confer a lower risk of intracranial bleeding than warfarin, although they do not have an antidote and their anticoagulant effect is difficult to monitor.

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Acknowledgments

Search strategy and selection criteria

References for this Review were identified through searches of PubMed by use of the search terms “warfarin” or “oral anticoagulation” and “intracranial hemorrhage”, from December 1986 to February 2011. Only papers in English were reviewed in detail. Further references were obtained from the bibliographies of the papers identified through our searches. The final reference list was generated on the basis of relevance to the topic of this Review.

Conflict of interest

Á Chamorro has given lectures and received consultancy fees from Servier, Sanofi-Synthelabo, Takeda, Bristol-Myers Squibb and Boehringer Ingelheim. Á Cervera has received consultancy fees from Boehringer Ingelheim. S Amaro declares to have no conflict of interests.

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  1. Comprehensive Stroke Center, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 170 Villarroel, 08036, Barcelona, Spain

    Álvaro Cervera, Sergio Amaro & Ángel Chamorro

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  1. Álvaro Cervera
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Correspondence to Ángel Chamorro.

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Cervera, Á., Amaro, S. & Chamorro, Á. Oral anticoagulant-associated intracerebral hemorrhage. J Neurol 259, 212–224 (2012). https://doi.org/10.1007/s00415-011-6153-3

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