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Major hemorrhages in patients treated with oral anticoagulants: choice of management in the emergency room

      Millions of people are treated with antithrombotic drugs and major hemorrhages are the most threatening consequence. When this study was performed the prevalence in the general population of people treated with vitamin K-antagonists (VKA) was approximately 1%, and major hemorrhagic events occurred in 2–3% of patients treated with VKA [
      • You J.
      • Singer D.
      • Howard P.
      • Lane D.
      • Eckman M.
      • Fang M.
      • Hilek E.
      • Schulman S.
      • Go A.
      • Hughes M.
      • Spencer F.
      • Manning W.
      • Halperin J.
      • Lip G.
      Antithrombotic therapy for atrial fibrillation: 9 th ed American college of Chest physicians evidence-based clinical practice guideline Chest.
      ,
      • Pisters R.
      • Lane D.
      • Nieuwlaat R.
      • Bde Vos C.
      • Crijns H.
      Lip G A novel user-friendly score (HAS-BLED) to assess 1 year risk of major bleeding in patients with atrial fibrillation: The Euro Heart.
      ,
      • Fang M.C.
      • et al.
      Death and disability from warfarin-associated intracranial and extracranial hemorrhages.
      ]. The mortality of intracranial hemorrhage (ICH) occurring on anticoagulant treatment is 30–55%, with a very high morbidity in surviving patients [
      • You J.
      • Singer D.
      • Howard P.
      • Lane D.
      • Eckman M.
      • Fang M.
      • Hilek E.
      • Schulman S.
      • Go A.
      • Hughes M.
      • Spencer F.
      • Manning W.
      • Halperin J.
      • Lip G.
      Antithrombotic therapy for atrial fibrillation: 9 th ed American college of Chest physicians evidence-based clinical practice guideline Chest.
      ,
      • Pisters R.
      • Lane D.
      • Nieuwlaat R.
      • Bde Vos C.
      • Crijns H.
      Lip G A novel user-friendly score (HAS-BLED) to assess 1 year risk of major bleeding in patients with atrial fibrillation: The Euro Heart.
      ,
      • Fang M.C.
      • et al.
      Death and disability from warfarin-associated intracranial and extracranial hemorrhages.
      ]. When bleeding occurs, treatment to reverse anticoagulation should be started as soon as possible. The reversal effect induced by oral or parenteral vitamin K is achieved no earlier than after 12–24 h and therefore it is not useful in life-threatening bleedings. Fresh frozen plasma (FFP) can be used but caution is necessary for the risk of volume overload. Concentrates containing three or four factors (II, VII, IX, X) of the Prothrombin Complex (CPC) can reverse the anticoagulation effect much more quickly [
      • Imberti D.
      • Barillari G.
      • Biasioli C.
      • Bianchi M.
      • Contino L.
      • Duce R.
      • D'Inca M.
      • Gnani M.
      • Mari E.
      • Ageno W.
      Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage Blood transfusion.
      ,
      • Majeed A.
      • Eelde A.
      • Agren A.
      • Schulman S.
      • Holmstrom M.
      Thromboembolic safety and efficacy of prothrombin complex concentrates in the emergency reversal of warfarin coagulopathy.
      ,
      • Sarode R.
      • Milling T.J.
      • Refaai M.A.
      • Mangione A.
      • Schneider A.
      • Durn B.L.
      • Goldstein J.N.
      Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized plasma controlled, phase IIIb study.
      ,
      • Makris M.
      • Van Veen J.
      Three or four factor prothrombin complex concentrate for emergency anticoagulation reversal?.
      ,
      • Kohler M.
      Thrombogenicity of prothrombin complex concentrates.
      ]. With this background, we performed an observational study in the Emergency Room (ER) of IRCCS Ca’ Granda Policlinico Hospital in Milan in order to evaluate how reversal therapies were used in patients taking VKA who bled. In our hospital, a protocol was developed according broadly to the international guidelines for the neutralization of VKA effects and is currently implemented with the supervision of a specialist of the Hemophilia and Thrombosis Center, who can be consulted 24/24 h. Our therapeutic options for reversal of VKA include vitamin K, CPC (3 or 4 factors) and Factor VII (FVII), whose utilization is at present off-label. FFP is currently hardly used, because CPC is the first-line therapy. In our protocol, the scheme of treatment of major bleeding is: discontinuation of VKA for at least 15 days; vitamin K 10–20 mg i.v.; CPC 35–50 UI/kg (sometime, for 3 factor products, associated to FVII 20 UI/kg), strict monitoring of the INR and the clinical course of the hemorrhage.

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