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Geographic variation in the reversal of vitamin K antagonist-associated coagulopathy


Serious bleeding is the most feared adverse effect of vitamin K antagonists (VKA) such as warfarin. VKA-treated patients who are bleeding (or found to have a supratherapeutic INR value) can be managed by administering one or more of the following: vitamin K, fresh frozen plasma, recombinant activated factor VII, or prothrombin complex concentrates. Current guidelines and review articles addressing this subject are discordant. We tested the hypothesis that significant clinical practice differences exist between North America and the rest of the world for reversal of VKA-associated coagulopathy.


A survey containing three hypothetical clinical cases was presented to attendees at a meeting of the International Society of Thrombosis and Haemostasis in July 2007. The respondents were primarily physicians with experience in anticoagulant management. The cases involved patients with an elevated INR value and either intracerebral bleeding, gastrointestinal bleeding, or no clinical evidence of bleeding. For each case, the attendee was asked to choose the intervention they would most probably order at their institution.


A total of 119 surveys were distributed and 46 were completed. See Table 1. For patients with intracerebral or gastrointestinal bleeding who required urgent reversal of VKA-associated coagulopathy, there was significantly greater use of fresh frozen plasma and recombinant activated factor VII in North America and significantly greater use of prothrombin complex concentrates in the rest of the world. For patients with an elevated INR but no bleeding, there was no significant difference in practice by geographic region; vitamin K was used consistently in all cases.

Table 1 Comparison by region of respondents recommending prothrombin complex concentrates for each case


Significant geographical differences exist in the way clinicians urgently reverse VKA-associated coagulopathy in bleeding patients. This suggests that randomized trials are needed to define optimal management strategies.

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Neal, M., Crowther, M., Douketis, J. et al. Geographic variation in the reversal of vitamin K antagonist-associated coagulopathy. Crit Care 12 (Suppl 2), P220 (2008).

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