Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage

详细信息    查看全文

• 作者：Jennifer A. Frontera ; John J. Lewin III ; Alejandro A. Rabinstein…
• 关键词：Anticoagulant ; Antiplatelet ; Antithrombotic ; Intracranial hemorrhage ; Intracerebral hemorrhage ; Intraparenchymal hemorrhage ; ICH ; Subarachnoid hemorrhage ; SAH ; Subdural hematoma ; SDH ; Reversal ; Antidote ; Vitamin K antagonist ; VKA ; Warfarin ; Coumadin ; Direct thrombin inhibitor ; DTI ; Dabigatran ; Factor Xa inhibitor ; Apixaban ; Rivaroxaban ; Edoxaban ; Low ; molecular weight heparin ; Heparin ; Heparinoid ; Pentasaccharide ; Fondaparinux ; TPA ; rtPA ; Alteplase ; Thrombolytic ; Plasminogen activator ; Aspirin ; C
• 刊名：Neurocritical Care
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：24
• 期：1
• 页码：6-46
• 全文大小：662 KB
• 参考文献：1.Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology. 2007;68:116–21.PubMed CrossRef
  2.Veltkamp R, Rizos T, Horstmann S. Intracerebral bleeding in patients on antithrombotic agents. Semin Thromb Hemost. 2013;39:963–71.PubMed CrossRef
  3.Franke CL, de Jonge J, van Swieten JC, Op de Coul AA, van Gijn J. Intracerebral hematomas during anticoagulant treatment. Stroke J Cereb Circ. 1990;21:726–30.CrossRef
  4.Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med. 2004;164:880–4.PubMed CrossRef
  5.Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63:1059–64.PubMed CrossRef
  6.Jaeschke R, Guyatt GH, Dellinger P, et al. Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. BMJ. 2008;337:a744.PubMed CrossRef
  7.Alexander PE, Gionfriddo MR, Li SA, et al. A number of factors explain why WHO guideline developers make strong recommendations inconsistent with GRADE guidance. J Clin Epidemiol. 2015. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​26399903 .
  8.Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64:380–2.PubMed CrossRef
  9.Guyatt GH, Schunemann HJ, Djulbegovic B, Akl EA. Guideline panels should not GRADE good practice statements. J Clin Epidemiol. 2015;68:597–600.PubMed CrossRef
  10.Brozek JL, Akl EA, Alonso-Coello P, et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. An overview of the GRADE approach and grading quality of evidence about interventions. Allergy. 2009;64:669–77.PubMed CrossRef
  11.Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke J Cereb Circ. 2005;36:1588–93.CrossRef
  12.Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S–98S.PubMed CrossRef
  13.Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89:635–41.PubMed CrossRef
  14.Chesebro JH, Fuster V. Optimal antithrombotic therapy for mechanical prosthetic heart valves. Circulation. 1996;94:2055–6.PubMed CrossRef
  15.Fihn SD, McDonell M, Martin D, et al. Risk factors for complications of chronic anticoagulation. A multicenter study. Warfarin Optimized Outpatient Follow-up Study Group. Ann Intern Med. 1993;118:511–20.PubMed CrossRef
  16.Wintzen AR, de Jonge H, Loeliger EA, Bots GT. The risk of intracerebral hemorrhage during oral anticoagulant treatment: a population study. Ann Neurol. 1984;16:553–8.PubMed CrossRef
  17.Palareti G, Leali N, Coccheri S, et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet. 1996;348:423–8.PubMed CrossRef
  18.Turpie AG, Gent M, Laupacis A, et al. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Engl J Med. 1993;329:524–9.PubMed CrossRef
  19.van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briet E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med. 1993;153:1557–62.PubMed CrossRef
  20.Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004;141:745–52.PubMed CrossRef
  21.Eckman MH, Rosand J, Knudsen KA, Singer DE, Greenberg SM. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke J Cereb Circ. 2003;34:1710–6.CrossRef
  22.Neau JP, Couderq C, Ingrand P, Blanchon P, Gil R, Group VGPS. Intracranial hemorrhage and oral anticoagulant treatment. Cerebrovasc Dis. 2001;11:195–200.PubMed CrossRef
  23.Punthakee X, Doobay J, Anand SS. Oral-anticoagulant-related intracerebral hemorrhage. Thromb Res. 2002;108:31–6.PubMed CrossRef
  24.Sjoblom L, Hardemark HG, Lindgren A, et al. Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study. Stroke J Cereb Circ. 2001;32:2567–74.CrossRef
  25.Hylek EM. Complications of oral anticoagulant therapy: bleeding and nonbleeding, rates and risk factors. Sem Vasc Med. 2003;3:271–8.CrossRef
  26.Fang MC, Go AS, Chang Y, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med. 2007;120:700–5.PubMedCentral PubMed CrossRef
  27.Berwaerts J, Webster J. Analysis of risk factors involved in oral-anticoagulant-related intracranial haemorrhages. QJM Mon J Assoc Phys. 2000;93:513–21.
  28.Fogelholm R, Eskola K, Kiminkinen T, Kunnamo I. Anticoagulant treatment as a risk factor for primary intracerebral haemorrhage. J Neurol Neurosurg Psychiatr. 1992;55:1121–4.PubMedCentral PubMed CrossRef
  29.Radberg JA, Olsson JE, Radberg CT. Prognostic parameters in spontaneous intracerebral hematomas with special reference to anticoagulant treatment. Stroke J Cereb Circ. 1991;22:571–6.CrossRef
  30.Kase CS, Robinson RK, Stein RW, et al. Anticoagulant-related intracerebral hemorrhage. Neurology. 1985;35:943–8.PubMed CrossRef
  31.Bair H, Ivascu F, Janczyk R, Nittis T, Bendick P, Howells G. Nurse driven protocol for head injured patients on warfarin. J Trauma nurs. 2005;12:120–6.PubMed CrossRef
  32.Hanger HC, Geddes JA, Wilkinson TJ, Lee M, Baker AE. Warfarin-related intracerebral haemorrhage: better outcomes when reversal includes prothrombin complex concentrates. Inter Med J. 2013;43:308–16.CrossRef
  33.Huttner HB, Schellinger PD, Hartmann M, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke J Cereb Circ. 2006;37:1465–70.CrossRef
  34.Fredriksson K, Norrving B, Stromblad LG. Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke J Cereb Circ. 1992;23:972–7.CrossRef
  35.Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality. J Trauma Injury Infect Crit Care. 2005;59(5):1131–9.CrossRef
  36.Kuramatsu JB, Gerner ST, Schellinger PD, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA. 2015;313:824–36.PubMed CrossRef
  37.Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P, Investigators C. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke J Cereb Circ. 2008;39:2993–6.CrossRef
  38.Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke J Cereb Circ. 2011;42:227–76.CrossRef
  39.Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke J Cereb Circ. 2011;42:1158–92.CrossRef
  40.Einhaupl K, Stam J, Bousser MG, et al. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol. 2010;17:1229–35.PubMed CrossRef
  41.Malhotra OP, Nesheim ME, Mann KG. The kinetics of activation of normal and gamma-carboxyglutamic acid-deficient prothrombins. J Biol Chem. 1985;260:279–87.PubMed
  42.Friedman PA, Rosenberg RD, Hauschka PV, Fitz-James A. A spectrum of partially carboxylated prothrombins in the plasmas of coumarin-treated patients. Biochim Biophys Acta. 1977;494:271–6.PubMed CrossRef
  43.Crowther MA, Wilson S. Vitamin K for the treatment of asymptomatic coagulopathy associated with oral anticoagulant therapy. J Thromb Thrombolysis. 2003;16:69–72.PubMed CrossRef
  44.Ageno W, Crowther M, Steidl L, et al. Low dose oral vitamin K to reverse acenocoumarol-induced coagulopathy: a randomized controlled trial. Thromb Haemost. 2002;88:48–51.PubMed
  45.Ageno W, Garcia D, Silingardi M, Galli M, Crowther M. A randomized trial comparing 1 mg of oral vitamin K with no treatment in the management of warfarin-associated coagulopathy in patients with mechanical heart valves. J Am Coll Cardiol. 2005;46:732–3.PubMed CrossRef
  46.Crowther MA, Ageno W, Schnurr T, et al. Oral vitamin K produces a normal INR within 24 hours of its administration in most patients discontinuing warfarin. Haematologica. 2005;90:137–9.PubMed
  47.Pengo V, Banzato A, Garelli E, Zasso A, Biasiolo A. Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation. Blood Coagul Fibrinolysis Int J Haemost Thromb. 1993;4:739–41.CrossRef
  48.Raj G, Kumar R, McKinney WP. Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione. Arch Intern Med. 1999;159:2721–4.PubMed CrossRef
  49.Lubetsky A, Hoffman R, Zimlichman R, et al. Efficacy and safety of a prothrombin complex concentrate (Octaplex) for rapid reversal of oral anticoagulation. Thromb Res. 2004;113:371–8.PubMed CrossRef
  50.Hung A, Singh S, Tait RC. A prospective randomized study to determine the optimal dose of intravenous vitamin K in reversal of over-warfarinization. Br J Haematol. 2000;109:537–9.PubMed CrossRef
  51.Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke J Cereb Circ. 1997;28:1–5.CrossRef
  52.Yasaka M, Sakata T, Minematsu K, Naritomi H. Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication. Thromb Res. 2002;108:25–30.PubMed CrossRef
  53.Lubetsky A, Yonath H, Olchovsky D, Loebstein R, Halkin H, Ezra D. Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch Intern Med. 2003;163:2469–73.PubMed CrossRef
  54.Watson HG, Baglin T, Laidlaw SL, Makris M, Preston FE. A comparison of the efficacy and rate of response to oral and intravenous Vitamin K in reversal of over-anticoagulation with warfarin. Br J Haematol. 2001;115:145–9.PubMed CrossRef
  55.Shetty HG, Backhouse G, Bentley DP, Routledge PA. Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1. Thromb Haemost. 1992;67:13–5.PubMed
  56.Cosgriff SW. The effectiveness of an oral vitamin K1 in controlling excessive hypoprothrombinemia during anticoagulant therapy. Ann Intern Med. 1956;45:14–22.PubMed CrossRef
  57.Yasaka M, Naritomi H, Minematsu K. Ischemic stroke associated with brief cessation of warfarin. Thromb Res. 2006;118:290–3.PubMed CrossRef
  58.Kalina M, Tinkoff G, Gbadebo A, Veneri P, Fulda G. A protocol for the rapid normalization of INR in trauma patients with intracranial hemorrhage on prescribed warfarin therapy. Am Surg. 2008;74:858–61.PubMed
  59.Frontera JA, Gordon E, Zach V, et al. Reversal of coagulopathy using prothrombin complex concentrates is associated with improved outcome compared to fresh frozen plasma in warfarin-associated intracranial hemorrhage. Neurocrit Care. 2014;21:397–406.PubMed CrossRef
  60.Whitling AM, Bussey HI, Lyons RM. Comparing different routes and doses of phytonadione for reversing excessive anticoagulation. Arch Intern Med. 1998;158:2136–40.PubMed CrossRef
  61.Nee R, Doppenschmidt D, Donovan DJ, Andrews TC. Intravenous versus subcutaneous vitamin K1 in reversing excessive oral anticoagulation. Am J Cardiol. 1999;83(286–8):A6–7.
  62.Mi YN, Ping NN, Xiao X, Zhu YB, Liu J, Cao YX. The severe adverse reaction to vitamin k1 injection is anaphylactoid reaction but not anaphylaxis. PLoS ONE. 2014;9:e90199.PubMedCentral PubMed CrossRef
  63.Riegert-Johnson DL, Volcheck GW. The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review. Ann Allergy Asthma Immunol. 2002;89:400–6.PubMed CrossRef
  64.Choonara IA, Scott AK, Haynes BP, Cholerton S, Breckenridge AM, Park BK. Vitamin K1 metabolism in relation to pharmacodynamic response in anticoagulated patients. Br J Clin Pharmacol. 1985;20:643–8.PubMedCentral PubMed CrossRef
  65.Butler JM, Groeger AW, Fletcher JS. Characterization of monochlorinated biphenyl products formed by Paul’s Scarlet Rose cells. Bull Environ Contam Toxicol. 1992;49:821–6.PubMed CrossRef
  66.de la Rubia J, Grau E, Montserrat I, Zuazu I, Paya A. Anaphylactic shock and vitamin K1. Ann Intern Med. 1989;110:943.PubMed CrossRef
  67.Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy: current practices and unresolved questions. Stroke J Cereb Circ. 2006;37:256–62.CrossRef
  68.Parry-Jones AR, Di Napoli M, Goldstein JN, et al. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage. Ann Neurol. 2015;78:54–62.PubMedCentral PubMed CrossRef
  69.Woo CH, Patel N, Conell C, et al. Rapid warfarin reversal in the setting of intracranial hemorrhage: a comparison of plasma, recombinant activated factor VII, and prothrombin complex concentrate. World Neurosurg. 2014;81:110–5.PubMed CrossRef
  70.Goldstein JN, Thomas SH, Frontiero V, et al. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke J Cereb Circ. 2006;37:151–5.CrossRef
  71.Ilyas C, Beyer GM, Dutton RP, Scalea TM, Hess JR. Recombinant factor VIIa for warfarin-associated intracranial bleeding. J Clin Anesth. 2008;20:276–9.PubMed CrossRef
  72.Lee SB, Manno EM, Layton KF, Wijdicks EF. Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP. Neurology. 2006;67:1272–4.PubMed CrossRef
  73.Chapman SA, Irwin ED, Beal AL, Kulinski NM, Hutson KE, Thorson MA. Prothrombin complex concentrate versus standard therapies for INR reversal in trauma patients receiving warfarin. Ann Pharmacother. 2011;45:869–75.PubMed CrossRef
  74.Makris M, Greaves M, Phillips WS, Kitchen S, Rosendaal FR, Preston EF. Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost. 1997;77:477–80.PubMed
  75.Hanley JP. Warfarin reversal. J Clin Pathol. 2004;57:1132–9.PubMedCentral PubMed CrossRef
  76.O’Shaughnessy DF, Atterbury C, Bolton Maggs P, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol. 2004;126:11–28.PubMed CrossRef
  77.Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S–98S.PubMed CrossRef
  78.Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009;145:24–33.PubMed CrossRef
  79.Chowdary P, Saayman AG, Paulus U, Findlay GP, Collins PW. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol. 2004;125:69–73.PubMed CrossRef
  80.Santagostino E, Mancuso ME, Morfini M, et al. Solvent/detergent plasma for prevention of bleeding in recessively inherited coagulation disorders: dosing, pharmacokinetics and clinical efficacy. Haematologica. 2006;91:634–9.PubMed
  81.Holland LL, Brooks JP. Toward rational fresh frozen plasma transfusion: the effect of plasma transfusion on coagulation test results. Am J Clin Pathol. 2006;126:133–9.PubMed CrossRef
  82.Dzik W, Rao A. Why do physicians request fresh frozen plasma? Transfusion. 2004;44:1393–4.PubMed CrossRef
  83.Ciavarella N, Antoncecchi S. D’Elia N [Dipyridamole and warfarin in patients with artificial heart valve prosthesis: double-blind tests]. Cardiologia. 1985;30:301–7.PubMed
  84.O’Reilly RA, Aggeler PM. Studies on coumarin anticoagulant drugs. Initiation of warfarin therapy without a loading dose. Circulation. 1968;38:169–77.PubMed CrossRef
  85.Sarode R, Milling TJ Jr, Refaai MA, et al. 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. Circulation. 2013;128:1234–43.PubMed
  86.Brody DL, Aiyagari V, Shackleford AM, Diringer MN. Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage. Neurocrit Care. 2005;2:263–7.PubMedCentral PubMed CrossRef
  87.Menzin J, White LA, Friedman M, et al. Factors associated with failure to correct the international normalised ratio following fresh frozen plasma administration among patients treated for warfarin-related major bleeding. An analysis of electronic health records. Thromb Haemost. 2012;107:662–72.PubMed CrossRef
  88.Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015;385(9982):2077–87.PubMed CrossRef
  89.Cervera A, Amaro S, Chamorro A. Oral anticoagulant-associated intracerebral hemorrhage. J Neurol. 2012;259:212–24.PubMed CrossRef
  90.Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation. 2013;128:360–4.PubMed CrossRef
  91.Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141:e152S–84S.PubMedCentral PubMed CrossRef
  92.Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke J Cereb Circ. 2010;41:2108–29.CrossRef
  93.Dowlatshahi D, Butcher KS, Asdaghi N, et al. Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke J Cereb Circ. 2012;43:1812–7.CrossRef
  94.Kuwashiro T, Yasaka M, Itabashi R, et al. Effect of prothrombin complex concentrate on hematoma enlargement and clinical outcome in patients with anticoagulant-associated intracerebral hemorrhage. Cerebrovasc Dis. 2011;31:170–6.PubMed CrossRef
  95.Steiner T, Freiberger A, Griebe M, et al. International normalised ratio normalisation in patients with coumarin-related intracranial haemorrhages–the INCH trial: a randomised controlled multicentre trial to compare safety and preliminary efficacy of fresh frozen plasma and prothrombin complex–study design and protocol. Int J Stroke. 2011;6:271–7.PubMed CrossRef
  96.Siddiq F, Jalil A, McDaniel C, et al. Effectiveness of Factor IX complex concentrate in reversing warfarin associated coagulopathy for intracerebral hemorrhage. Neurocrit Care. 2008;8:36–41.PubMed CrossRef
  97.Majeed A, Meijer K, Larrazabal R, et al. Mortality in vitamin K antagonist-related intracerebral bleeding treated with plasma or 4-factor prothrombin complex concentrate. Thromb Haemost. 2014;111:233–9.PubMed CrossRef
  98.Edavettal M, Rogers A, Rogers F, Horst M, Leng W. Prothrombin complex concentrate accelerates international normalized ratio reversal and diminishes the extension of intracranial hemorrhage in geriatric trauma patients. Am Surg. 2014;80:372–6.PubMed
  99.Cabral KP, Fraser GL, Duprey J, et al. Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding. Clin Neurol Neurosurg. 2013;115:770–4.PubMed CrossRef
  100.Switzer JA, Rocker J, Mohorn P, et al. Clinical experience with three-factor prothrombin complex concentrate to reverse warfarin anticoagulation in intracranial hemorrhage. Stroke J Cereb Circ. 2012;43:2500–2.CrossRef
  101.Wojcik C, Schymik ML, Cure EG. Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy. Int J Emerg Med. 2009;2:217–25.PubMedCentral PubMed CrossRef
  102.Stewart WS, Pettit H. Experiences with an activated 4-factor prothrombin complex concentrate (FEIBA) for reversal of warfarin-related bleeding. Am J Emerg Med. 2013;31:1251–4.PubMed CrossRef
  103.CSL Behring. Full Prescribing Information: Kcentra® Prothrombin Complex Concentrate (Human). CSL Behring Gmbh; 2014.
  104.Sarode R, Matevosyan K, Bhagat R, Rutherford C, Madden C, Beshay JE. Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage. J Neurosurg. 2012;116:491–7.PubMed CrossRef
  105.Aledort LM. Factor VIII inhibitor bypassing activity (FEIBA)—addressing safety issues. Haemophilia. 2008;14:39–43.PubMed CrossRef
  106.Freeman WD, Brott TG, Barrett KM, et al. Recombinant factor VIIa for rapid reversal of warfarin anticoagulation in acute intracranial hemorrhage. Mayo Clin Proc. 2004;79:1495–500.PubMed CrossRef
  107.Jaffe J, AlKhawam L, Du H, et al. Outcome predictors and spectrum of treatment eligibility with prospective protocolized management of intracerebral hemorrhage. Neurosurgery. 2009;64:436–45; discussion 45–6.
  108.Pinner NA, Hurdle AC, Oliphant C, Reaves A, Lobo B, Sills A. Treatment of warfarin-related intracranial hemorrhage: a comparison of prothrombin complex concentrate and recombinant activated factor VII. World Neurosurg. 2010;74:631–5.PubMed CrossRef
  109.Brown CV, Sowery L, Curry E, et al. Recombinant factor VIIa to correct coagulopathy in patients with traumatic brain injury presenting to outlying facilities before transfer to the regional trauma center. Am Surg. 2012;78:57–60.PubMed
  110.Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity. J Thromb Haemost. 2004;2:1700–8.PubMed CrossRef
  111.Butenas S, Brummel KE, Branda RF, Paradis SG, Mann KG. Mechanism of factor VIIa-dependent coagulation in hemophilia blood. Blood. 2002;99:923–30.PubMed CrossRef
  112.O’Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA. 2006;295:293–8.PubMed CrossRef
  113.Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–37.PubMed CrossRef
  114.Refaai MA, Goldstein JN, Lee ML, Durn BL, Milling TJ Jr, Sarode R. Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal. Transfusion. 2015;15(11):2722–9.CrossRef
  115.Guest JF, Watson HG, Limaye S. Modeling the cost-effectiveness of prothrombin complex concentrate compared with fresh frozen plasma in emergency warfarin reversal in the United kingdom. Clin Ther. 2010;32:2478–93.PubMed CrossRef
  116. Jones CA, Ducis K, Petrozzino J, et al. Prevention of treatment-related fluid overload reduces estimated effective cost of prothrombin complex concentrate in patients requiring rapid vitamin K antagonist reversal. Expert Rev Pharmacoecon Outcomes Res. 2015:1–5.
  117.Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A, Ostermann H. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost. 2008;6(4):622–31.PubMed CrossRef
  118.Voils SA, Baird B. Systematic review: 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal: does it matter? Thromb Res. 2012;130(6):833–40.PubMed CrossRef
  119.Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369:799–808.PubMed CrossRef
  120.Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699–708.PubMed CrossRef
  121.Bruins Slot KM, Berge E. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. The. Cochrane Database Syst Rev. 2013;8:CD008980.PubMed
  122.Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17.PubMed CrossRef
  123.Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.PubMed CrossRef
  124.Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.PubMed CrossRef
  125.Hokusai VTEI, Buller HR, Decousus H, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406–15.CrossRef
  126.Investigators E, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510.CrossRef
  127.Investigators E-P, Buller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287–97.CrossRef
  128.Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.PubMed CrossRef
  129.Kaatz S, Kouides PA, Garcia DA, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(Suppl 1):S141–5.PubMed CrossRef
  130.Wang X, Mondal S, Wang J, et al. Effect of activated charcoal on apixaban pharmacokinetics in healthy subjects. Am J Cardiovasc Drugs. 2014;14:147–54.PubMedCentral PubMed CrossRef
  131.Food and Drug Administration. Advisory committee briefing book: rivaroxaban. 2015. http://​www.​fda.​gov/​downloads/​AdvisoryCommitte​es/​CommitteesMeetin​gMaterials/​Drugs/​Cardiovascular/​Cardiovascularan​dRenalDrugsAdvis​ory%20​Commitee/​UCM138385.​pdf ). Accessed 2 Feb 2015.
  132.Crowther M, Crowther MA. Antidotes for novel oral anticoagulants: current status and future potential. Arterioscler Thromb Vasc Biol. 2015;35(8):1736–45.PubMed CrossRef
  133.Zhou W, Zorn M, Nawroth P, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke J Cereb Circ. 2013;44:771–8.CrossRef
  134.Perzborn E, Gruber A, Tinel H, et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost. 2013;110:162–72.PubMed CrossRef
  135.Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–9.PubMed CrossRef
  136.Perzborn E, Heitmeier S, Laux V, Buchmuller A. Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro. Thromb Res. 2014;133:671–81.PubMed CrossRef
  137.Dinkelaar J, Molenaar PJ, Ninivaggi M, de Laat B, Brinkman HJ, Leyte A. In vitro assessment, using thrombin generation, of the applicability of prothrombin complex concentrate as an antidote for Rivaroxaban. J Thromb Haemost. 2013;11:1111–8.PubMed CrossRef
  138.Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012;108:217–24.PubMed CrossRef
  139.Herrmann R, Thom J, Wood A, Phillips M, Muhammad S, Baker R. Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban. Thromb Haemost. 2014;111:989–95.PubMed CrossRef
  140.Arellano-Rodrigo E, Lopez-Vilchez I, Galan AM, et al. Coagulation factor concentrates fail to restore alterations in fibrin formation caused by rivaroxaban or dabigatran in studies with flowing blood from treated healthy volunteers. Transfus Med Rev. 2015;29:242–9.PubMed CrossRef
  141.Dibu JR, Weimer JM, Ahrens C, Manno E, Frontera JA. The role of FEIBA in reversing novel oral anticoagulants in intracerebral hemorrhage. Neurocrit Care. 2015. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​26545367 .
  142.Maurice-Szamburski A, Graillon T, Bruder N. Favorable outcome after a subdural hematoma treated with feiba in a 77-year-old patient treated by rivaroxaban. J Neurosurg Anesthesiol. 2014;26:183.PubMed CrossRef
  143.Kiraly A, Lyden A, Periyanayagam U, Chan J, Pang PS. Management of hemorrhage complicated by novel oral anticoagulants in the emergency department: case report from the northwestern emergency medicine residency. Am J Ther. 2013;20:300–6.PubMed
  144.Korber MK, Langer E, Ziemer S, Perzborn E, Gericke C, Heymann C. Measurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro study. Clin Appl Thromb Hemost. 2014;20:735–40.PubMed CrossRef
  145.Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E, et al. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood. PLoS ONE. 2013;8:e78696.PubMedCentral PubMed CrossRef
  146.Godier A, Miclot A, Le Bonniec B, et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology. 2012;116:94–102.PubMed CrossRef
  147.Martin AC, Le Bonniec B, Fischer AM, et al. Evaluation of recombinant activated factor VII, prothrombin complex concentrate, and fibrinogen concentrate to reverse apixaban in a rabbit model of bleeding and thrombosis. Int J Cardiol. 2013;168:4228–33.PubMed CrossRef
  148.Fukuda T, Honda Y, Kamisato C, Morishima Y, Shibano T. Reversal of anticoagulant effects of edoxaban, an oral, direct factor Xa inhibitor, with haemostatic agents. Thromb Haemost. 2012;107:253–9.PubMed CrossRef
  149.Halim AB, Samama MM, Mendell J. Ex vivo reversal of the anticoagulant effects of edoxaban. Thromb Res. 2014;134:909–13.PubMed CrossRef
  150.Herzog E, Kaspereit F, Krege W, et al. Effective reversal of edoxaban-associated bleeding with four-factor prothrombin complex concentrate in a rabbit model of acute hemorrhage. Anesthesiology. 2015;122:387–98.PubMed CrossRef
  151.Zahir H, Brown KS, Vandell AG, et al. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation. 2015;131:82–90.PubMed CrossRef
  152.Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.PubMed CrossRef
  153.Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342–52.PubMed CrossRef
  154.Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368:709–18.PubMed CrossRef
  155.Lewis BE, Wallis DE, Leya F, Hursting MJ, Kelton JG, Argatroban I. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003;163:1849–56.PubMed CrossRef
  156.Hart RG, Diener HC, Yang S, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke J Cereb Circ. 2012;43:1511–7.CrossRef
  157.Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206–14.PubMed CrossRef
  158.Zhou W, Schwarting S, Illanes S, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke J Cereb Circ. 2011;42:3594–9.CrossRef
  159.Lauer A, Cianchetti FA, Van Cott EM, et al. Anticoagulation with the oral direct thrombin inhibitor dabigatran does not enlarge hematoma volume in experimental intracerebral hemorrhage. Circulation. 2011;124:1654–62.PubMedCentral PubMed CrossRef
  160.Tanoue S, Inamasu J, Yamada M, Toyama H, Hirose Y. Does Dabigatran Increase the Risk of Delayed Hematoma Expansion in a Rat Model of Collagenase-induced Intracerebral Hemorrhage? J Stroke Cerebrovasc Dis. 2015;24:374–80.PubMed CrossRef
  161.Lexi-comp. Lexicomp Online. Hudson, OH, 2015.
  162.Komori M, Yasaka M, Kokuba K, et al. Intracranial hemorrhage during dabigatran treatment. Circ J. 2014;78:1335–41.PubMed CrossRef
  163.van Ryn J, Seiger P, Kink-Eiband M, Gansser D, Clemens A. Adsorption of dabigatran etexilate in water or dabigatran in pooled human plasma by activated charcoal in vitro. [Abstract no 1065] In: 51st ASH annual meeting and exposition [website]. New Orleans, LA: American Society of Hematology; 2009. http://​ash.​confex.​com/​ash/​2009/​webprogram/​Paper21383.​html .
  164.Food and Drug Administration. Idaruczumab. 2015. http://​www.​fda.​gov/​Drugs/​InformationOnDru​gs/​ApprovedDrugs/​ucm467396.​htm . Accessed 12 Nov 2015.
  165.Pharmaceuticals BI. Full Prescribing Information: Praxbind®. Boehringer Ingelheim International GmbH; 2015.
  166.Schiele F, van Ryn J, Canada K, et al. A specific antidote for dabigatran: functional and structural characterization. Blood. 2013;121:3554–62.PubMed CrossRef
  167.van Ryn JS, Schmoll M, Pillu H, et al. Effect of dabigatran on the ability to generate fibrin at a wound site and its reversal by idarucizumab, the antidote to dabigatran, in healthy volunteers: an exploratory marker of blood loss. Circulation. 2014;130(Suppl 2):18403.
  168.Grottke O, van Ryn J, Spronk HM, Rossaint R. Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care. 2014;18:R27.PubMedCentral PubMed CrossRef
  169. Honickel M, Treutler S, van Ryn J, Tillmann S, Rossaint R, Grottke O. Reversal of dabigatran anticoagulation ex vivo: porcine study comparing prothrombin complex concentrates and idarucizumab. Thromb Haemost. 2015;113(4):728–40.PubMed CrossRef
  170.Glund S, Moschetti V, Norris S, et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015;113:943–51.PubMed CrossRef
  171.Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015;386(9994):680–90.PubMed CrossRef
  172.Glund SS, J.; Schmohl, M.; et. al. Idarucizumab, a specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in elderly and renally impaired subjects. Am Soc Hematol. 2014;344 (abstract).
  173.Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511–20.PubMed CrossRef
  174.Greinacher A, Thiele T, Selleng K. Reversal of anticoagulants: an overview of current developments. Thromb Haemost. 2015;113:931–42.PubMed CrossRef
  175.Herzog E, Kaspereit FJ, Krege W, et al. Thrombotic safety of prothrombin complex concentrate (Beriplex P/N) for dabigatran reversal in a rabbit model. Thromb Res. 2014;134:729–36.PubMed CrossRef
  176.Lambourne MD, Eltringham-Smith LJ, Gataiance S, Arnold DM, Crowther MA, Sheffield WP. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost. 2012;10:1830–40.PubMed CrossRef
  177.Pragst I, Zeitler SH, Doerr B, et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. J Thromb Haemost. 2012;10:1841–8.PubMed CrossRef
  178.Khoo TL, Weatherburn C, Kershaw G, Reddel CJ, Curnow J, Dunkley S. The use of FEIBA(R) in the correction of coagulation abnormalities induced by dabigatran. Int J Lab Hematol. 2013;35:222–4.PubMed CrossRef
  179.Hoffman M, Volovyk Z, Monroe DM. Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate. Anesthesiology. 2015;122:353–62.PubMed CrossRef
  180.Lindahl TL, Wallstedt M, Gustafsson KM, Persson E, Hillarp A. More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate. Thromb Res. 2015;135:544–7.PubMed CrossRef
  181.Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity. Crit Care Med. 2013;41:e42–6.PubMed CrossRef
  182.Puttick T, Bahl R, Mohamedbhai H. Emergency reversal of dabigatran for emergency surgery. BMJ Case Rep. 2015. http://​casereports.​bmj.​com/​content/​2015/​bcr-2014-209057.​full.​pdf .
  183.Wong H, Keeling D. Activated prothrombin complex concentrate for the prevention of dabigatran-associated bleeding. Br J Haematol. 2014;166:152–3.PubMed CrossRef
  184.Schulman S, Ritchie B, Goy JK, Nahirniak S, Almutawa M, Ghanny S. Activated prothrombin complex concentrate for dabigatran-associated bleeding. Br J Haematol. 2014;164:308–10.PubMed CrossRef
  185.Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625–51.PubMed CrossRef
  186.Weitz JI, Quinlan DJ, Eikelboom JW. Periprocedural management and approach to bleeding in patients taking dabigatran. Circulation. 2012;126:2428–32.PubMed CrossRef
  187.Bobbitt L, Merriman E, Raynes J, Henderson R, Blacklock H, Chunilal S. PROTHROMBINEX((R))-VF (PTX-VF) usage for reversal of coagulopathy: prospective evaluation of thrombogenic risk. Thromb Res. 2011;128:577–82.PubMed CrossRef
  188.Dentali F, Marchesi C, Pierfranceschi MG, et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A Meta-analysis. Thromb Haemost. 2011;106:429–38.PubMed CrossRef
  189.Franchini M, Lippi G. Prothrombin complex concentrates: an update. Blood Transfus = Trasfusione del sangue. 2010;8:149–54.PubMed
  190.Imberti D, Magnacavallo A, Dentali F, et al. Emergency reversal of anticoagulation with vitamin K antagonists with 3-factor prothrombin complex concentrates in patients with major bleeding. J Thromb Thrombolysis. 2013;36:102–8.PubMed CrossRef
  191.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. Thromb Res. 2012;129:146–51.PubMed CrossRef
  192.Song HK, Tibayan FA, Kahl EA, et al. Safety and efficacy of prothrombin complex concentrates for the treatment of coagulopathy after cardiac surgery. J Thorac Cardiovasc Surg. 2014;147:1036–40.PubMed CrossRef
  193.Song MM, Warne CP, Crowther MA. Prothrombin complex concentrate (PCC, Octaplex) in patients requiring immediate reversal of vitamin K antagonist anticoagulation. Thromb Res. 2012;129:526–9.PubMed CrossRef
  194.Toth P, Makris M. Prothrombin complex concentrate-related thrombotic risk following anticoagulation reversal. Thromb Haemost. 2012;107:599.PubMed CrossRef
  195.Kumar R, Smith RE, Henry BL. A review of and recommendations for the management of patients with life-threatening dabigatran-associated hemorrhage: a single-center university hospital experience. J Intensive Care Med. 2015;30(8):462–72.PubMed CrossRef
  196.Singh T, Maw TT, Henry BL, et al. Extracorporeal therapy for dabigatran removal in the treatment of acute bleeding: a single center experience. Clin J Am Soc Nephrol. 2013;8:1533–9.PubMedCentral PubMed CrossRef
  197.Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49:259–68.PubMed CrossRef
  198.Khadzhynov D, Wagner F, Formella S, et al. Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in patients with end-stage renal disease. Thromb Haemost. 2013;109:596–605.PubMed CrossRef
  199.Chang DN, Dager WE, Chin AI. Removal of dabigatran by hemodialysis. Am J Kidney Dis. 2013;61:487–9.PubMed CrossRef
  200.Osgood M, Compton R, Carandang R, Hall W, Kershaw G, Muehlschlegel S. Rapid unexpected brain herniation in association with renal replacement therapy in acute brain injury: caution in the neurocritical care unit. Neurocrit Care. 2015;22:176–83.PubMed CrossRef
  201.Davenport A. Changing the hemodialysis prescription for hemodialysis patients with subdural and intracranial hemorrhage. Hemodialysis Int Symp Home Hemodialysis. 2013;17(Suppl 1):S22–7.CrossRef
  202.Fletcher JJ, Bergman K, Carlson G, Feucht EC, Blostein PA. Continuous renal replacement therapy for refractory intracranial hypertension? J Trauma. 2010;68:1506–9.PubMed CrossRef
  203.Fletcher JJ, Bergman K, Feucht EC, Blostein P. Continuous renal replacement therapy for refractory intracranial hypertension. Neurocrit Care. 2009;11:101–5.PubMed CrossRef
  204.Lin CM, Lin JW, Tsai JT, et al. Intracranial pressure fluctuation during hemodialysis in renal failure patients with intracranial hemorrhage. Acta Neurochir Suppl. 2008;101:141–4.PubMed CrossRef
  205.Antman EM, Morrow DA, McCabe CH, et al. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006;354:1477–88.PubMed CrossRef
  206.Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996;334:677–81.PubMed CrossRef
  207.Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med. 1996;334:682–7.PubMed CrossRef
  208.Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997;337:447–52.PubMed CrossRef
  209.Racanelli A, Fareed J. Neutralization of the antithrombotic effects of heparin and Fraxiparin by protamine sulfate. Thromb Res. 1992;68:211–22.PubMed CrossRef
  210.Michalski R, Lane DA, Pepper DS, Kakkar VV. Neutralization of heparin in plasma by platelet factor 4 and protamine sulphate. Br J Haematol. 1978;38:561–71.PubMed CrossRef
  211.Levy JH, Cormack JG, Morales A. Heparin neutralization by recombinant platelet factor 4 and protamine. Anesth Analg. 1995;81:35–7.PubMed
  212.Silver PJ, Broughton R, Bouthillier J, Quinn TA, Wallace AM, Weishaar RE. Neutralase reverses the anti-coagulant but not the anti-thrombotic activity of heparin in a rabbit model of venous thrombosis. Thromb Res. 1998;91:143–50.PubMed CrossRef
  213.Jaques LB, Charles A, Best C. The administration of heparin. Acta Med Scand. 1938;90:190.
  214.Chargaff E, Olson KB. Studies on the chemistry of blood coagulation: studies on the action of heparin and other anti-coagulants; the influence of protamine on the anticoagulant effect in vivo. J Biol Chem. 1937;122:153–67.
  215.Lillehei CW, Sterns LP, Long DM, Lepley D. Comparative study of polybrene and protamine for heparin neutralization in open heart surgery. Ann Surg. 1960;151(1):11–6.PubMedCentral PubMed
  216.Lindblad B, Borgstrom A, Wakefield TW, Whitehouse WM Jr, Stanley JC. Haemodynamic and haematologic alterations with protamine reversal of anticoagulation: comparison of standard heparin and a low molecular weight heparin fragment. Eur J Vasc Sur. 1987;1:181–5.CrossRef
  217.Racanelli A, Fareed J. Ex vivo activity of heparin is not predictive of blood loss after neutralization by protamine. Thromb Res. 1992;67:263–73.PubMed CrossRef
  218.Parkin TW, Kvale WF. Neutralization of the anticoagulant effects of heparin with protamine (salmine). Am Heart J. 1949;37:333–42.PubMed CrossRef
  219.Andrassy K, Eschenfelder V, Weber E. Neutralization of the anticoagulant activity of low molecular weight heparin LU 47311 (Clivarin) in man by protamine chloride. Thromb Res. 1994;73:85–93.PubMed CrossRef
  220.Kikura M, Lee MK, Levy JH. Heparin neutralization with methylene blue, hexadimethrine, or vancomycin after cardiopulmonary bypass. Anesth Analg. 1996;83:223–7.PubMed
  221.Dehmer GJ, Haagen D, Malloy CR, Schmitz JM. Anticoagulation with heparin during cardiac catheterization and its reversal by protamine. Cathet Cardiovasc Diagn. 1987;13:16–21.PubMed CrossRef
  222.Dehmer GJ, Lange RA, Tate DA, et al. Randomized trial of recombinant platelet factor 4 versus protamine for the reversal of heparin anticoagulation in humans. Circulation. 1996;94:II347–52.PubMed
  223.Stafford-Smith M, Lefrak EA, Qazi AG, et al. Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass. Anesthesiology. 2005;103:229–40.PubMed CrossRef
  224.Wolzt M, Weltermann A, Nieszpaur-Los M, et al. Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man. Thromb Haemost. 1995;73:439–43.PubMed
  225.Gatti G, Pugliese P. Heparin reversal in off-pump coronary artery bypass surgery: complete, partial, or no reversal? Cardiovasc Surg. 2002;10:245–50.PubMed CrossRef
  226.Dorman BH, Elliott BM, Spinale FG, et al. Protamine use during peripheral vascular surgery: a prospective randomized trial. J Vasc Surg. 1995;22:248–55 discussion 56.PubMed CrossRef
  227.Hull RD, Raskob GE, Hirsh J, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis. N Engl J Med. 1986;315:1109–14.PubMed CrossRef
  228.Hawksley M. De-heparinisation of blood after cardiopulmonary bypass. Lancet. 1966;1:563–5.PubMed CrossRef
  229.Lowary LR, Smith FA, Coyne E, Dunham NW. Comparative neutralization of lung- and mucosal-derived heparin by protamine sulfate using in vitro and in vivo methods. J Pharm Sci. 1971;60:638–40.PubMed CrossRef
  230.Jaques LB. A study of the toxicity of the protamine, salmine. Br J Pharmacol Chemother. 1949;4:135–44.PubMedCentral PubMed CrossRef
  231.Estes JW. The kinetics of heparin. Ann N Y Acad Sci. 1971;179:187–204.PubMed CrossRef
  232.Guffin AV, Dunbar RW, Kaplan JA, Bland JW Jr. Successful use of a reduced dose of protamine after cardiopulmonary bypass. Anesth Analg. 1976;55:110–3.PubMed CrossRef
  233.Cushman M, Lim W, Zakai NA. 2011 Clinical Practice guide on anticoagulant dosing and management of anticoagulant-associated bleeding complications in Adults. Am Soc Hematol. 2011. http://​www.​hematology.​org/​Clinicians/​Guidelines-Quality/​Quick-Ref/​525.​aspx . Accessed 12 Nov 2015.
  234.Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: american College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:141S–59S.PubMed CrossRef
  235.Pharmacists ASoH-S. Protamine sulfate: antiheparin agents. Bethesda, MD: American Society of Health-system Pharmacists;1999.
  236.Fresenius Kabi USA. Full Prescribing Information: Protamine Sulfate Injection, USP. PremierPro Rx; 2013.
  237.Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e227S–77S.PubMedCentral PubMed CrossRef
  238.Adkins JR, Hardy JD. Sodium heparin neutralization and the anticoagulant effects of protamine sulfate. Arch Surg. 1967;94:175–7.PubMed CrossRef
  239.Egerton WS, Robinson CL. The anti-heparin, anticoagulant and hypotensive properties of hexadimethrine and protamine. Lancet. 1961;2:635–7.PubMed CrossRef
  240.Andersen MN, Mendelow M, Alfano GA. Experimental studies of heparin-protamine activity with special reference to protamine inhibition of clotting. Surgery. 1959;46:1060–8.PubMed
  241.Hirsh J, Guyatt G, Albers GW, Harrington R, Schunemann HJ, American College of Chest P. Antithrombotic and thrombolytic therapy: american college of chest physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133:110S–2S.PubMed CrossRef
  242.Chen KC, Payne D, Lazo-Langner A, Ross I, Kiaii B. Successful intraoperative reversal of heparin with factor VII in a patient with protamine reaction. Innovations. 2011;6:48–50.PubMed
  243.Lauritzen B, Hedner U, Johansen PB, Tranholm M, Ezban M. Recombinant human factor VIIa and a factor VIIa-analogue reduces heparin and low molecular weight heparin (LMWH)-induced bleeding in rats. J Thromb Haemost. 2008;6:804–11.PubMed CrossRef
  244.Jaschinski U, Ried M, Lichtwarck-Aschoff M, Forst H. Bleeding diathesis due to failed antagonism of heparin: successful treatment with recombinant factor VIIa. Anesth Analg. 2004;99:1872.PubMed CrossRef
  245.von Heymann C, Hotz H, Konertz W, Kox WJ, Spies C. Successful treatment of refractory bleeding with recombinant factor VIIa after redo coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2002;16:615–6.CrossRef
  246.Garcia DA, Baglin TP, Weitz JI, Samama MM, American College of Chest P. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141:e24S–43S.PubMedCentral PubMed CrossRef
  247.Dolovich LR, Ginsberg JS, Douketis JD, Holbrook AM, Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med. 2000;160:181–8.PubMed CrossRef
  248.van Dongen CJ, van den Belt AGM, Prins MH, Lensing AWA. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. 2004. doi:10.​1002/​14651858.​CD001100.​pub2 .PubMed
  249.Group PIftCCCT, the A, New Zealand Intensive Care Society Clinical Trials G, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011;364:1305–14.
  250.Sherman DG, Albers GW, Bladin C, et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Lancet. 2007;369:1347–55.PubMed CrossRef
  251.Diener HC, Ringelstein EB, von Kummer R, et al. Prophylaxis of thrombotic and embolic events in acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the PROTECT Trial. Stroke J Cereb Circul. 2006;37:139–44.CrossRef
  252.Shorr AF, Jackson WL, Sherner JH, Moores LK. Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis. Chest. 2008;133:149–55.PubMed CrossRef
  253.Agnelli G, Piovella F, Buoncristiani P, et al. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med. 1998;339:80–5.PubMed CrossRef
  254.Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med. 1999;341:793–800.PubMed CrossRef
  255.Douketis J, Cook D, Meade M, et al. Prophylaxis against deep vein thrombosis in critically ill patients with severe renal insufficiency with the low-molecular-weight heparin dalteparin: an assessment of safety and pharmacodynamics: the DIRECT study. Arch Intern Med. 2008;168:1805–12.PubMed CrossRef
  256.Gatt A, van Veen JJ, Woolley AM, Kitchen S, Cooper P, Makris M. Thrombin generation assays are superior to traditional tests in assessing anticoagulation reversal in vitro. Thromb Haemost. 2008;100:350–5.PubMed
  257.Crowther MA, Berry LR, Monagle PT, Chan AK. Mechanisms responsible for the failure of protamine to inactivate low-molecular-weight heparin. Br J Haematol. 2002;116:178–86.PubMed CrossRef
  258.Holst J, Lindblad B, Bergqvist D, et al. Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers. Blood Coagul Fibrinolysis Int J Haemost Thromb. 1994;5:795–803.CrossRef
  259.Xu Y, Cai C, Chandarajoti K, et al. Homogeneous low-molecular-weight heparins with reversible anticoagulant activity. Nat Chem Biol. 2014;10:248–50.PubMedCentral PubMed CrossRef
  260.Harenberg J, Siegele M, Dempfle CE, Stehle G, Heene DL. Protamine neutralization of the release of tissue factor pathway inhibitor activity by heparins. Thromb Haemost. 1993;70:942–5.PubMed
  261.Holst J, Lindblad B, Bergqvist D, Hedner U, Nordfang O, Ostergaard P. The effect of protamine sulphate on plasma tissue factor pathway inhibitor released by intravenous and subcutaneous unfractionated and low molecular weight heparin in man. Thromb Res. 1997;86:343–8.PubMed CrossRef
  262.Massonnet-Castel S, Pelissier E, Bara L, et al. Partial reversal of low molecular weight heparin (PK 10169) anti-Xa activity by protamine sulfate: in vitro and in vivo study during cardiac surgery with extracorporeal circulation. Haemostasis. 1986;16:139–46.PubMed
  263.Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ. Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin. Blood. 1991;78:2337–43.PubMed
  264.Diness V, Ostergaard PB. Neutralization of a low molecular weight heparin (LHN-1) and conventional heparin by protamine sulfate in rats. Thromb Haemost. 1986;56:318–22.PubMed
  265.Van Ryn-McKenna J, Cai L, Ofosu FA, Hirsh J, Buchanan MR. Neutralization of enoxaparine-induced bleeding by protamine sulfate. Thromb Haemost. 1990;63:271–4.PubMed
  266.van Veen JJ, Maclean RM, Hampton KK, et al. Protamine reversal of low molecular weight heparin: clinically effective? Blood Coagul Fibrinolysis Int J Haemost Thromb. 2011;22:565–70.CrossRef
  267.Makris M, Hough RE, Kitchen S. Poor reversal of low molecular weight heparin by protamine. Br J Haematol. 2000;108:884–5.PubMed CrossRef
  268.Sanofi-Aventis U.S. Full Prescribing Information: Lovenox®. Sanofi-Aventis U.S., LLC; 2013.
  269.Pfizer, Inc. Full Prescribing Information: Fragmin®. Pfizer Labs; 2015.
  270.Leo Pharmaceutical Products. Full Prescribing Information: Innohep®. Leo Pharma, Inc.; 2008.
  271.Gerotziafas GT, Zafiropoulos A, Van Dreden P, et al. Inhibition of factor VIIa generation and prothrombin activation by treatment with enoxaparin in patients with unstable angina. Br J Haematol. 2003;120:611–7.PubMed CrossRef
  272.Young G, Yonekawa KE, Nakagawa PA, Blain RC, Lovejoy AE, Nugent DJ. Recombinant activated factor VII effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin ex vivo as measured using thromboelastography. Blood Coagul Fibrinolysis Int J Haemost Thromb. 2007;18:547–53.CrossRef
  273.Chan S, Kong M, Minning DM, Hedner U, Marder VJ. Assessment of recombinant factor VIIa as an antidote for bleeding induced in the rabbit by low molecular weight heparin. J Thromb Haemost. 2003;1:760–5.PubMed CrossRef
  274.Firozvi K, Deveras RA, Kessler CM. Reversal of low-molecular-weight heparin-induced bleeding in patients with pre-existing hypercoagulable states with human recombinant activated factor VII concentrate. Am J Hematol. 2006;81:582–9.PubMed CrossRef
  275.Wang CH, Chen YC, Tsao CW, Yang SS. Dalteparin-associated catastrophic retroperitoneal hematoma successfully treated with recombinant factor VIIa. Int Urol Nephrol. 2012;44:1091–5.PubMed CrossRef
  276.Cherfan A, Arabi Y. Al Askar A, Al Shimemeri A. Recombinant activated factor VII treatment of retroperitoneal hematoma in a patient with renal failure receiving enoxaparin and clopidogrel. Pharmacotherapy. 2007;27:755–9.PubMed CrossRef
  277.Byrne M, Zumberg M. Intentional low-molecular-weight heparin overdose: a case report and review. Blood Coagul Fibrinolysis Int J Haemost Thromb. 2012;23:772–4.CrossRef
  278.Vavra KA, Lutz MF, Smythe MA. Recombinant factor VIIa to manage major bleeding from newer parenteral anticoagulants. Ann Pharmacother. 2010;44:718–26.PubMed CrossRef
  279.Ng HJ, Koh LP, Lee LH. Successful control of postsurgical bleeding by recombinant factor VIIa in a renal failure patient given low molecular weight heparin and aspirin. Ann Hematol. 2003;82:257–8.PubMed
  280.Culic S, Kuljis D, Armanda V, Jankovic S. Successful management of bleeding with recombinant factor VIIa (NovoSeven) in a patient with Burkitt lymphoma and thrombosis of the left femoral and left common iliac veins. Pediatr Blood Cancer. 2007;49:332–5.PubMed CrossRef
  281.Hu Q, Brady JO. Recombinant activated factor VII for treatment of enoxaparin-induced bleeding. Mayo Clin Proc. 2004;79:827.PubMed CrossRef
  282.Schmid P, Brodmann D, Odermatt Y, Fischer AG, Wuillemin WA. Study of bioaccumulation of dalteparin at a therapeutic dose in patients with renal insufficiency. J Thromb Haemost. 2009;7:1629–32.PubMed CrossRef
  283.Oudemans-van Straaten HM, Bosman RJ, Koopmans M, et al. Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med. 2009;37:545–52.PubMed CrossRef
  284.Schmid P, Brodmann D, Fischer AG, Wuillemin WA. Study of bioaccumulation of dalteparin at a prophylactic dose in patients with various degrees of impaired renal function. J Thromb Haemost. 2009;7:552–8.PubMed CrossRef
  285.Chawla LS, Moore G, Seneff MG. Incomplete reversal of enoxaparin toxicity by protamine: implications of renal insufficiency, obesity, and low molecular weight heparin sulfate content. Obes Surg. 2004;14:695–8.PubMed CrossRef
  286.Egger SS, Sawatzki MG, Drewe J, Krahenbuhl S. Life-threatening hemorrhage after dalteparin therapy in a patient with impaired renal function. Pharmacotherapy. 2005;25:881–5.PubMed CrossRef
  287.Mismetti P, Laporte-Simitsidis S, Navarro C, et al. Aging and venous thromboembolism influence the pharmacodynamics of the anti-factor Xa and anti-thrombin activities of a low molecular weight heparin (nadroparin). Thromb Haemost. 1998;79:1162–5.PubMed
  288.Lim W, Cook DJ, Crowther MA. Safety and efficacy of low molecular weight heparins for hemodialysis in patients with end-stage renal failure: a meta-analysis of randomized trials. J Am Soc Nephrol. 2004;15:3192–206.PubMed CrossRef
  289.Oudemans-van Straaten HM, van Schilfgaarde M, Molenaar PJ, Wester JP, Leyte A. Hemostasis during low molecular weight heparin anticoagulation for continuous venovenous hemofiltration: a randomized cross-over trial comparing two hemofiltration rates. Crit Care. 2009;13:R193.PubMedCentral PubMed CrossRef
  290.Nigten J, de Groot KA, Grootendorst DC, Koolen SL, Herruer MH, Schut NH. Pharmacokinetics of dalteparin during haemodialysis. Nephron Clin Pract. 2013;124:179–83.PubMed CrossRef
  291.de Valk HW, Banga JD, Wester JW, et al. Comparing subcutaneous danaparoid with intravenous unfractionated heparin for the treatment of venous thromboembolism. A randomized controlled trial. Ann Intern Med. 1995;123:1–9.PubMed CrossRef
  292.Meuleman DG. Orgaran (Org 10172): its pharmacological profile in experimental models. Haemostasis. 1992;22:58–65.PubMed
  293.Funk DM. Coagulation assays and anticoagulant monitoring. Hematology/the Education Program of the American Society of Hematology American Society of Hematology Education Program; 2012:460–5.
  294.Turpie AG, Gent M, Cote R, et al. A low-molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study. Ann Intern Med. 1992;117:353–7.PubMed CrossRef
  295.Dumas R, Woitinas F, Kutnowski M, et al. A multicentre, double-blind, randomized study to compare the safety and efficacy of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein thrombosis in patients with acute ischaemic stroke. Age Ageing. 1994;23:512–6.PubMed CrossRef
  296.Low molecular weight heparinoid. ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. JAMA. 1998;279:1265–72.CrossRef
  297.Schmahl KS, Ganjoo AK, Harloff MG. Orgaran (Org 10172) for cardiopulmonary bypass in heparin-induced thrombocytopenia: role of adjunctive plasmapheresis. J Cardiothorac Vasc Anesth. 1997;11:262–3.PubMed CrossRef
  298.Decousus H, Prandoni P, Mismetti P, et al. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. N Engl J Med. 2010;363:1222–32.PubMed CrossRef
  299.Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141:e152S–84S.PubMedCentral PubMed CrossRef
  300.Nagler M, Haslauer M, Wuillemin WA. Fondaparinux—data on efficacy and safety in special situations. Thromb Res. 2012;129:407–17.PubMed CrossRef
  301.Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ. 2006;332:325–9.PubMedCentral PubMed CrossRef
  302.Choay J, Petitou M, Lormeau JC, Sinay P, Casu B, Gatti G. Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem Biophys Res Commun. 1983;116:492–9.PubMed CrossRef
  303.Beguin S, Choay J, Hemker HC. The action of a synthetic pentasaccharide on thrombin generation in whole plasma. Thromb Haemost. 1989;61:397–401.PubMed
  304.Buller HR, Davidson BL, Decousus H, et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003;349:1695–702.PubMed CrossRef
  305.Warkentin TE, Crowther MA. Reversing anticoagulants both old and new. Can J Anaesth. 2002;49:S11–25.PubMed
  306.Elmer J, Wittels KA. Emergency reversal of pentasaccharide anticoagulants: a systematic review of the literature. Transfus Med. 2012;22:108–15.PubMed CrossRef
  307.Desmurs-Clavel H, Huchon C, Chatard B, Negrier C, Dargaud Y. Reversal of the inhibitory effect of fondaparinux on thrombin generation by rFVIIa, aPCC and PCC. Thromb Res. 2009;123:796–8.PubMed CrossRef
  308.Corbonnois G, Martin M, Hacquard M, et al. Fondaparinux reversal with activated prothrombin complex concentrate in anesthetised bleeding rats. Thromb Haemost. 2013;109:560–3.PubMed CrossRef
  309.Godier A, Durand M, Emmerich J, Dizier B, Lecompte T, Samama CM. Efficacy of prothrombin complex concentrate to reverse the anticoagulant effect of the pentasaccharide fondaparinux in a rabbit model. Thromb Haemost. 2011;105:161–8.PubMed CrossRef
  310.Bijsterveld NR, Moons AH, Boekholdt SM, et al. Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation. 2002;106:2550–4.PubMed CrossRef
  311.Bijsterveld NR, Vink R, van Aken BE, et al. Recombinant factor VIIa reverses the anticoagulant effect of the long-acting pentasaccharide idraparinux in healthy volunteers. Br J Haematol. 2004;124:653–8.PubMed CrossRef
  312.Lisman T, Bijsterveld NR, Adelmeijer J, et al. Recombinant factor VIIa reverses the in vitro and ex vivo anticoagulant and profibrinolytic effects of fondaparinux. J Thromb Haemost. 2003;1:2368–73.PubMed CrossRef
  313.Gerotziafas GT, Depasse F, Chakroun T, Samama MM, Elalamy I. Recombinant factor VIIa partially reverses the inhibitory effect of fondaparinux on thrombin generation after tissue factor activation in platelet rich plasma and whole blood. Thromb Haemost. 2004;91:531–7.PubMed
  314.Lisman T, Adelmeijer J, Nieuwenhuis HK, de Groot PG. Enhancement of fibrinolytic potential in vitro by anticoagulant drugs targeting activated factor X, but not by those inhibiting thrombin or tissue factor. Blood Coagul Fibrinolysis Int J Haemost Thromb. 2003;14:557–62.CrossRef
  315.Luporsi P, Chopard R, Janin S, et al. Use of recombinant factor VIIa (NovoSeven((R))) in 8 patients with ongoing life-threatening bleeding treated with fondaparinux. Acute Card Care. 2011;13:93–8.PubMed CrossRef
  316.Moser M, Nordt T, Peter K, et al. Platelet function during and after thrombolytic therapy for acute myocardial infarction with reteplase, alteplase, or streptokinase. Circulation. 1999;100:1858–64.PubMed CrossRef
  317.Sun X, Berthiller J, Trouillas P, Derex L, Diallo L, Hanss M. Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis. J Neurol Sci. 2015;351:109–14.PubMed CrossRef
  318.Sun X, Berthiller J, Derex L, Trouillas P, Diallo L, Hanss M. Post-thrombolysis haemostasis changes after rt-PA treatment in acute cerebral infarct. Correlations with cardioembolic aetiology and outcome. J Neurol Sci. 2015;349:77–83.PubMed CrossRef
  319.Mueller HS, Rao AK, Forman SA. Thrombolysis in myocardial infarction (TIMI): comparative studies of coronary reperfusion and systemic fibrinogenolysis with two forms of recombinant tissue-type plasminogen activator. J Am Coll Cardiol. 1987;10:479–90.PubMed CrossRef
  320.Topol EJ, Morris DC, Smalling RW, et al. A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (activase) in acute myocardial infarction. J Am Coll Cardiol. 1987;9:1205–13.PubMed CrossRef
  321.Matrat A, De Mazancourt P, Derex L, et al. Characterization of a severe hypofibrinogenemia induced by alteplase in two patients thrombolysed for stroke. Thromb Res. 2013;131:e45–8.PubMed CrossRef
  322.Trouillas P, Derex L, Philippeau F, et al. Early fibrinogen degradation coagulopathy is predictive of parenchymal hematomas in cerebral rt-PA thrombolysis: a study of 157 cases. Stroke J Cereb Circ. 2004;35:1323–8.CrossRef
  323.Beer J, Coller BS. Evidence that platelet glycoprotein IIIa has a large disulfide-bonded loop that is susceptible to proteolytic cleavage. J Biol Chem. 1989;264:17564–73.PubMed
  324.Hoffmann JJ. Blood viscosity and platelet function in thrombolytic therapy of acute myocardial infarction. Eur Heart J. 1990;11(Suppl F):29–35.
  325.Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581–7.
  326.Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke J Cereb Circ. 2013;44:870–947.CrossRef
  327.Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317–29.PubMed CrossRef
  328.Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347:1143–50.PubMed CrossRef
  329.O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61:e78–140.PubMed CrossRef
  330.Semba CP, Bakal CW, Calis KA, et al. Alteplase as an alternative to urokinase. Advisory panel on catheter-directed thrombolytic therapy. J Vasc Interv Radiol. 2000;11:279–87.PubMed CrossRef
  331.Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006;113:e463–654.PubMed CrossRef
  332.Bruen KJ, Ballard JR, Morris SE, Cochran A, Edelman LS, Saffle JR. Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy. Arch Surg. 2007;142:546–51 discussion 51-3.PubMed CrossRef
  333.Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann HJ. Executive summary: antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:7S–47S.PubMedCentral PubMed CrossRef
  334.Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:2440–92.PubMed CrossRef
  335.Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365:518–26.PubMed CrossRef
  336.Cohen A. Pharmacokinetics of the recombinant thrombolytic agents: what is the clinical significance of their different pharmacokinetic parameters? BioDrugs Clin Immunother Biopharm Gene Ther. 1999;11:115–23.
  337.Eisenberg PR, Sherman LA, Tiefenbrunn AJ, Ludbrook PA, Sobel BE, Jaffe AS. Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation. Thromb Haemost. 1987;57:35–40.PubMed
  338.Larsen GR, Metzger M, Henson K, Blue Y, Horgan P. Pharmacokinetic and distribution analysis of variant forms of tissue-type plasminogen activator with prolonged clearance in rat. Blood. 1989;73:1842–50.PubMed
  339.Longstaff C, Williams S, Thelwell C. Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem. 2008;6:212–23.PubMed CrossRef
  340.Nilsson S, Einarsson M, Ekvarn S, Haggroth L, Mattsson C. Turnover of tissue plasminogen activator in normal and hepatectomized rabbits. Thromb Res. 1985;39:511–21.PubMed CrossRef
  341.Tanswell P, Modi N, Combs D, Danays T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet. 2002;41:1229–45.PubMed CrossRef
  342.Chapman DF, Lyden P, Lapchak PA, Nunez S, Thibodeaux H, Zivin J. Comparison of TNK with wild-type tissue plasminogen activator in a rabbit embolic stroke model. Stroke J Cereb Circ. 2001;32:748–52.CrossRef
  343.Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384:1929–35.PubMedCentral PubMed CrossRef
  344.Hill MD, Buchan AM, Canadian Alteplase for Stroke Effectiveness Study I. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ Canad Med Assoc = journal journal de l’Association medicale canadienne. 2005;172:1307–12.CrossRef
  345.Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA. 2000;283:1145–50.PubMed CrossRef
  346.Mazya M, Egido JA, Ford GA, et al. Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score. Stroke. 2012;43:1524–31.PubMed CrossRef
  347. http://​online.​lexi.​com/​lco/​action/​api/​find/​globalid/​5595?​utd=​1 ). Accessed 8 July 2015.
  348.Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317–29.PubMed CrossRef
  349.Goldstein JN, Marrero M, Masrur S, et al. Management of thrombolysis-associated symptomatic intracerebral hemorrhage. Arch Neurol. 2010;67:965–9.PubMedCentral PubMed CrossRef
  350.Yaghi S, Boehme AK, Dibu J, et al. Treatment and outcome of thrombolysis-related hemorrhage: a multicenter retrospective study. JAMA Neurol. 2015;26:1–7.
  351.Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007;38:2001–23.PubMed CrossRef
  352.Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:870–947.PubMed CrossRef
  353.Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004;104:1243–52.PubMed CrossRef
  354.Spahn DR, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17:R76.PubMedCentral PubMed CrossRef
  355.Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion. 2014;54:1389–405 (quiz 8).PubMed CrossRef
  356.Alderazi YJ, Barot NV, Peng H, et al. Clotting factors to treat thrombolysis-related symptomatic intracranial hemorrhage in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23:e207–14.PubMedCentral PubMed CrossRef
  357.Yaghi S, Eisenberger A, Willey JZ. Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis with intravenous recombinant tissue plasminogen activator: a review of natural history and treatment. JAMA Neurol. 2014;71:1181–5.PubMedCentral PubMed CrossRef
  358.French KF, White J, Hoesch RE. Treatment of intracerebral hemorrhage with tranexamic acid after thrombolysis with tissue plasminogen activator. Neurocrit Care. 2012;17:107–11.PubMed CrossRef
  359.Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Predictors of mortality in trauma patients with intracranial hemorrhage on preinjury aspirin or clopidogrel. J Trauma. 2008;65:785–8.PubMed CrossRef
  360.Roquer J, Rodriguez Campello A, Gomis M, Ois A, Puente V, Munteis E. Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage. J Neurol. 2005;252:412–6.PubMed CrossRef
  361.Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen ER, Hillbom M. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke. 2006;37:129–33.PubMed CrossRef
  362.Toyoda K, Okada Y, Minematsu K, et al. Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage. Neurology. 2005;65:1000–4.PubMed CrossRef
  363.Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J Trauma. 2008;65:1303–8.PubMed CrossRef
  364.Ahmed N, Bialowas C, Kuo YH, Zawodniak L. Impact of preinjury anticoagulation in patients with traumatic brain injury. South Med J. 2009;102:476–80.PubMed CrossRef
  365.Fortuna GR, Mueller EW, James LE, Shutter LA, Butler KL. The impact of preinjury antiplatelet and anticoagulant pharmacotherapy on outcomes in elderly patients with hemorrhagic brain injury. Surgery. 2008;144:598–603 (Discussion-5).PubMed CrossRef
  366.Sansing LH, Messe SR, Cucchiara BL, et al. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology. 2009;72:1397–402.PubMedCentral PubMed CrossRef
  367.Caso V, Paciaroni M, Venti M, et al. Effect of on-admission antiplatelet treatment on patients with cerebral hemorrhage. Cerebrovasc Dis. 2007;24:215–8.PubMed CrossRef
  368.Moussouttas M, Malhotra R, Fernandez L, et al. Role of antiplatelet agents in hematoma expansion during the acute period of intracerebral hemorrhage. Neurocrit Care. 2010;12:24–9.PubMed CrossRef
  369.Memon MA, Blankenship JC, Wood GC, Frey CM, Menapace FJ. Incidence of intracranial hemorrhage complicating treatment with glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis of major clinical trials. Am J Med. 2000;109:213–7.PubMed CrossRef
  370.Campbell PG, Sen A, Yadla S, Jabbour P, Jallo J. Emergency reversal of antiplatelet agents in patients presenting with an intracranial hemorrhage: a clinical review. World Neurosurg. 2010;74:279–85.PubMed CrossRef
  371.Sinzinger H, Fitscha P, Peskar BA. Platelet half-life, plasma thromboxane-B2 and circulating endothelial-cells in peripheral vascular-disease. Angiology. 1986;37:112–8.PubMed CrossRef
  372.Grossman CM, Macewan AM, Dilley J. The halflife of human platelet phosphatide. Nature. 1960;188:950–1.PubMed CrossRef
  373.Li X, Sun Z, Zhao W, et al. Effect of acetylsalicylic acid usage and platelet transfusion on postoperative hemorrhage and activities of daily living in patients with acute intracerebral hemorrhage. J Neurosurg. 2013;118:94–103.PubMed CrossRef
  374.Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005;365:387–97.PubMed CrossRef
  375.Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013;382(9890):397–408.PubMedCentral PubMed CrossRef
  376.Naidech AM, Liebling SM, Rosenberg NF, et al. Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage. Neurocrit Care. 2012;16:82–7.PubMed CrossRef
  377.Washington CW, Schuerer DJ, Grubb RL Jr. Platelet transfusion: an unnecessary risk for mild traumatic brain injury patients on antiplatelet therapy. J Trauma. 2011;71:358–63.PubMed CrossRef
  378.Joseph B, Pandit V, Sadoun M, et al. A prospective evaluation of platelet function in patients on antiplatelet therapy with traumatic intracranial hemorrhage. J Trauma Acute Care. 2013;75:990–4.CrossRef
  379.Ducruet AF, Hickman ZL, Zacharia BE, et al. Impact of platelet transfusion on hematoma expansion in patients receiving antiplatelet agents before intracerebral hemorrhage. Neurol Res. 2010;32:706–10.PubMed CrossRef
  380.Leong LB, David TK. Is platelet transfusion effective in patients taking antiplatelet agents who suffer an intracranial hemorrhage? J Emerg Med. 2015;49(4):561–72.PubMed CrossRef
  381.Kim DY, O’Leary M, Nguyen A, et al. The effect of platelet and desmopressin administration on early radiographic progression of traumatic intracranial hemorrhage. J Neurotrauma. 2015;32:1815–21.PubMed CrossRef
  382.Naidech AM, Rosenberg NF, Bernstein RA, Batjer HH. Aspirin use or reduced platelet activity predicts craniotomy after intracerebral hemorrhage. Neurocrit Care. 2011;15:442–6.PubMed CrossRef
  383.Naidech AM, Bendok BR, Garg RK, et al. Reduced platelet activity is associated with more intraventricular hemorrhage. Neurosurgery. 2009;65:684–8 (Discussion 8).PubMed CrossRef
  384.Naidech AM, Bernstein RA, Levasseur K, et al. Platelet activity and outcome after intracerebral hemorrhage. Ann Neurol. 2009;65:352–6.PubMed CrossRef
  385.Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med. 2010;362:600–13.PubMedCentral PubMed CrossRef
  386.Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood. 2009;113:3406–17.PubMed CrossRef
  387.Creutzfeldt CJ, Weinstein JR, Longstreth WT Jr, Becker KJ, McPharlin TO, Tirschwell DL. Prior antiplatelet therapy, platelet infusion therapy, and outcome after intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2009;18:221–8.PubMedCentral PubMed CrossRef
  388.Naidech AM, Jovanovic B, Liebling S, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke. 2009;40:2398–401.PubMed CrossRef
  389.Tcheng JE. Clinical challenges of platelet glycoprotein IIb/IIIa receptor inhibitor therapy: bleeding, reversal, thrombocytopenia, and retreatment. Am Heart J. 2000;139:S38–45.PubMed CrossRef
  390.Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404–13.PubMed CrossRef
  391.Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366:20–33.PubMed CrossRef
  392.de Gans K, de Haan RJ, Majoie CB, et al. PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial. BMC Neurol. 2010;10:19.PubMedCentral PubMed CrossRef
  393.Zeigler ZR, Megaludis A, Fraley DS. Desmopressin (d-DAVP) effects on platelet rheology and von Willebrand factor activities in uremia. Am J Hematol. 1992;39:90–5.PubMed CrossRef
  394.Gordz S, Mrowietz C, Pindur G, Park JW, Jung F. Effect of desmopressin (DDAVP) on platelet membrane glycoprotein expression in patients with von Willebrand’s disease. Clin Hemorheol Microcirc. 2005;32:83–7.PubMed
  395.Calmer S, Ferkau A, Larmann J, et al. Desmopressin (DDAVP) improves recruitment of activated platelets to collagen but simultaneously increases platelet endothelial interactions in vitro. Platelets. 2014;25:8–15.PubMed CrossRef
  396.Mannucci PM, Remuzzi G, Pusineri F, et al. Deamino-8-d -arginine vasopressin shortens the bleeding time in uremia. N Engl J Med. 1983;308:8–12.PubMed CrossRef
  397.Kim JH, Baek CH, Min JY, Kim JS, Kim SB, Kim H. Desmopressin improves platelet function in uremic patients taking antiplatelet agents who require emergent invasive procedures. Ann Hematol. 2015;94:1457–61.PubMed CrossRef
  398.Reiter R, Jilma-Stohlawetz P, Horvath M, Jilma B. Additive effects between platelet concentrates and desmopressin in antagonizing the platelet glycoprotein IIb/IIIa inhibitor eptifibatide. Transfusion. 2005;45:420–6.PubMed CrossRef
  399.Reiter RA, Mayr F, Blazicek H, et al. Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. Blood. 2003;102:4594–9.PubMed CrossRef
  400.Naidech AM, Maas MB, Levasseur-Franklin KE, et al. Desmopressin improves platelet activity in acute intracerebral hemorrhage. Stroke J Cereb Circ. 2014;45:2451–3.CrossRef
  401.Cattaneo M, Lombardi R, Bettega D, Lecchi A, Mannucci PM. Shear-induced platelet aggregation is potentiated by desmopressin and inhibited by ticlopidine. Arterioscler Thromb. 1993;13:393–7.PubMed CrossRef
  402.Leithauser B, Zielske D, Seyfert UT, Jung F. Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel. Clin Hemorheol Microcirc. 2008;39:293–302.PubMed
  403.Mannucci PM, Vicente V, Vianello L, et al. Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time. Blood. 1986;67:1148–53.PubMed
  404.Ranucci M, Nano G, Pazzaglia A, Bianchi P, Casana R, Tealdi DG. Platelet mapping and desmopressin reversal of platelet inhibition during emergency carotid endarterectomy. J Cardiothorac Vasc Anesth. 2007;21:851–4.PubMed CrossRef
  405.Teng R, Mitchell PD, Butler K. The effect of desmopressin on bleeding time and platelet aggregation in healthy volunteers administered ticagrelor. J Clin Pharm Ther. 2014;39:186–91.PubMed CrossRef
  406.Flordal PA, Sahlin S. Use of desmopressin to prevent bleeding complications in patients treated with aspirin. Br J Surg. 1993;80:723–4.PubMed CrossRef
  407.Keyl C, Kmitta E, Kueri S, Zietak T, Trenk D. Effects of aspirin and desmopressin on platelet reactivity in patients undergoing cardiac surgery with extracorporeal circulation. Thromb Haemost. 2011;105:113–21.PubMed CrossRef
  408.Lethagen S, Olofsson L, Frick K, Berntorp E, Bjorkman S. Effect kinetics of desmopressin-induced platelet retention in healthy volunteers treated with aspirin or placebo. Haemophilia. 2000;6:15–20.PubMed CrossRef
  409.Schulz-Stubner S, Zielske D, Rossaint R. Comparison between nasal and intravenous desmopressin for the treatment of aminosalicylic acid-induced platelet dysfunction. Eur J Anaesthesiol. 2002;19:647–51.PubMed CrossRef
  410.Tsui PY, Cheung CW, Lee Y, Leung SW, Ng KF. The effectiveness of low-dose desmopressin in improving hypothermia-induced impairment of primary haemostasis under influence of aspirin—a randomized controlled trial. BMC Anesthesiol. 2015;15:80.PubMedCentral PubMed CrossRef
  411.Swieringa F, Lance MD, Fuchs B, et al. Desmopressin treatment improves platelet function under flow in patients with postoperative bleeding. J Thromb Haemost. 2015;13:1503–13.PubMed CrossRef
  412.Wademan BH, Galvin SD. Desmopressin for reducing postoperative blood loss and transfusion requirements following cardiac surgery in adults. Interact CardioVasc Thorac Surg. 2014;18:360–70.PubMedCentral PubMed CrossRef
  413.Jin L, Ji HW. Effect of desmopressin on platelet aggregation and blood loss in patients undergoing valvular heart surgery. Chin Med J (Engl). 2015;128:644–7.CrossRef
  414.Ansell J, Klassen V, Lew R, et al. Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study. J Thorac Cardiovasc Surg. 1992;104:117–23.PubMed
  415.Clagett GP, Valentine RJ, Myers SI, Chervu A, Heller J. Does desmopressin improve hemostasis and reduce blood loss from aortic surgery? A randomized, double-blind study. J Vasc Surg. 1995;22:223–9 discussion 9-30.PubMed CrossRef
  416.Kapapa T, Rohrer S, Struve S, et al. Desmopressin acetate in intracranial haemorrhage. Neurol Res Int. 2014;2014:298767.PubMedCentral PubMed CrossRef
  417.Van Herzeele C, De Bruyne P, Evans J, et al. Safety profile of desmopressin tablet for enuresis in a prospective study. Adv Ther. 2014;31:1306–16.PubMed CrossRef
  418.Desmopressin. 2015. http://​www.​wolterskluwercdi​.​com/​lexicomp-online/​ . Accessed 8 July 2015.
  419.Altman R, Scazziota A. M DELH, Gonzalez C. Recombinant factor VIIa reverses the inhibitory effect of aspirin or aspirin plus clopidogrel on in vitro thrombin generation. J Thromb Haemost. 2006;4:2022–7.PubMed CrossRef
  420.McMillian WD, Rogers FB. Management of prehospital antiplatelet and anticoagulant therapy in traumatic head injury: a review. J Trauma. 2009;66:942–50.PubMed CrossRef
  421.Li YF, Spencer FA, Becker RC. Comparative efficacy of fibrinogen and platelet supplementation on the in vitro reversibility of competitive glycoprotein IIb/IIIa receptor-directed platelet inhibition. Am Heart J. 2002;143:725–32.PubMed CrossRef
  422.Schunemann HJ, Oxman AD, Brozek J, et al. GRADE: assessing the quality of evidence for diagnostic recommendations. ACP J Club. 2008;149:2.PubMed
  423.Micromedex. Micromedex healthcare series. 2015 ed. Greenwood Village, CO.: Thomson Micromedex.; 2015.
  424.Ansell JE, Bakhru SH, Laulicht BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014;371:2141–2.PubMed CrossRef
  425.Bakhru SH, Laulicht B, Jiang X, et al. Reversal of anticoagulant-induced bleeding in external and internal bleeding models by PER977, a small molecule anticoagulant antidote. Circulation. 2014;130:A19361 (abstract).
  426.Laulicht B, Bakhru S, Lee C, et al. Small molecule antidote for anticoagulants. Circulation. 2012;126(21 Supplement):A11395 abstract.
  427.Laulicht BB S, Jiang X, et. al. Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977. Presented at the 24th Congress of the International Society on Thrombosis and Hemostasis, abstract 2013.
  428.Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19:446–51.PubMed CrossRef
  429.Crowther MAK, M; Lorenz, T, et. al. A phase 2 randomized, double blind placebo controlled trial of PRT064445, a novel, universal antidote for direct and indirect factor Xa inhibitors. 55th ASH annual meeting, New Orleans 2013; abstract.
  430.Crowther MA, Lu G, Conley P, et al. Sustained reversal of apixaban anticoagulation with andexanet alpha using a bolus plus infusion regimen in a phase II placebo controlled trial. Eur Heart J. 2014;35(Suppl):137 (abstract).
  431.Crowther MAL, Lu G, et al. A phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of edoxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), a Universal Antidote for Factor Xa (FXa) Inhibitors. ASH 2014; Abstract 4269.
  432.Crowther MAL, Lu G, et al. ANNEXA-A: a phase 3 randomized, double-blind, placebo-controlled trial, demonstrating reversal of apixaban-induced anticoagulation in older subjects by andexanet alfa (PRT064445), a Universal Antidote for Facotr Xa (fXa) Inhibitors. AHA 2014;CS.03 (abstract).
  433.Crowther MAM, V.; Kitt, M; et. al. A phase 2 randomized, double blind placebo controlled trial demonstrating reversal of rivaroxaban-induced anticoagulation in healthy subjects by andexanet alpha (PRT064445), an antidote for factor Xa inhibitors. 55th ASH annual meeting, New Orleans 2013; abstract.
  434.Pollack CV Jr, Reilly PA, Bernstein R, et al. Design and rationale for RE-VERSE AD: a phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost. 2015;114:198–205.PubMed CrossRef
  
• 作者单位：Jennifer A. Frontera (1)
  John J. Lewin III (2)
  Alejandro A. Rabinstein (3)
  Imo P. Aisiku (4)
  Anne W. Alexandrov (5) (6)
  Aaron M. Cook (7)
  Gregory J. del Zoppo (8)
  Monisha A. Kumar (9)
  Ellinor I. B. Peerschke (10)
  Michael F. Stiefel (11)
  Jeanne S Teitelbaum (12)
  Katja E. Wartenberg (13)
  Cindy L. Zerfoss (14)
  
  1. The Cerebrovascular Center, Neurological Institute, Cleveland Clinic and Case Western Reserve University, 9500 Euclid Ave. S80, Cleveland, OH, 44195, USA
  2. The Departments of Pharmacy and Anesthesiology & Critical Care Medicine, The Johns Hopkins Hospital and Johns Hopkins University School of Medicine, Baltimore, MD, USA
  3. The Department of Neurology, Mayo Clinic, Rochester, MN, USA
  4. Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
  5. The University of Tennessee Health Science Center, Memphis, TN, USA
  6. Australian Catholic University, Sydney, Australia
  7. Department of Pharmacy (UK Healthcare) & Department of Pharmacy Practice & Science (UK College of Pharmacy), University of Kentucky, Lexington, KY, USA
  8. The Departments of Medicine (Hematology) and Neurology, University of Washington School of Medicine, Seattle, WA, USA
  9. The Departments of Neurology, Neurosurgery, Anesthesiology & Critical Care, Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
  10. The Department of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical School, New York, NY, USA
  11. The Department of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY, USA
  12. Hôpital du Sacré-Coeur and University of Montreal and Montreal Neurological Institute and McGill University, Montreal, Quebec, Canada
  13. Klinik für Neurologie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany
  14. The Neuroscience and Neurosurgery Departments, Centra Lynchburg General Hospital, Lynchburg, VA, USA
  
• 刊物主题：Internal Medicine; Neurology;
• 出版者：Springer US
• ISSN：1556-0961

文摘

Background The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.