SPECIAL ARTICLE
Treatment of Warfarin-Associated Intracerebral Hemorrhage: Literature Review and Expert Opinion

https://doi.org/10.4065/82.1.82Get rights and content

Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent decades. In contrast to spontaneous ICH, the duration of bleeding is 12 to 24 hours in many patients, offering a longer opportunity for intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor VIIa only (2 experts) to recombinant factor VIIa along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.

Section snippets

METHODS

A computerized search of the OVID database from January 1996 to January 2006 combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage was undertaken. The reference lists from recent review articles were also examined. From the elicited sources, 4 of the coauthors (R.G.H., C.S.K., M.I.A., and W.D.F.) drafted the narrative review of the recent literature. Because information about the practical clinical pharmacology of prothrombin complex

Frequency of Warfarin-Associated ICH

Warfarin-associated ICH is not rare at hospitals that serve large numbers of patients undergoing anticoagulation and appears to be increasing.2 A survey of consecutive patients with supratentorial ICH admitted to the Massachusetts General Hospital between 1994 and 2001 found that 24% were taking warfarin, an average of 1 patient per month with warfarin-associated ICH admitted to this tertiary care hospital.16 Other studies of ICH in the middle to late 1990s reported that approximately 12%

DISCUSSION

Warfarin-associated ICH is a devastating iatrogenic problem whose frequency is increasing because more elderly people are receiving anticoagulation. It is a tragic irony that anticoagulation given to prevent ischemic stroke can be complicated by severe, usually lethal, hemorrhagic stroke as its most dreaded complication. In the absence of randomized trials, management is based on a combination of anecdotal experience, pathophysiologic constructs, and expert opinion. Not surprisingly, the

CONCLUSION

Reasonable management of warfarin-associated ICH includes a range of treatments in the absence of adequate data, as defined by the expert opinions delineated herein. Time to reversal of anticoagulation is crucial, and whatever treatment strategy is endorsed should be planned in advance in collaboration with local emergency medicine physicians and be used expeditiously. Randomized trials that address the management of warfarin-associated ICH are needed.

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    NovoNordisk manufactures recombinant factor VIIa. Drs Mayer, Rosand, and Steiner have served as consultants to NovoNordisk and are members of the Recombinant Factor VII ICH Study Team.

    All authored materials constitute the personal statements of Maj Barbara J. Hoeben and are not intended to constitute an endorsement by Wilford Hall Medical Center, Lackland AFB, or any other federal government entity.

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