Semin Neurol 2016; 36(03): 274-287
DOI: 10.1055/s-0036-1582133
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Diagnosis and Management of Coagulopathy-Related Intracerebral Hemorrhage

Joshua VanDerWerf
1   Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
,
Monisha A. Kumar
1   Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
› Author Affiliations
Further Information

Publication History

Publication Date:
23 May 2016 (online)

Abstract

Coagulopathy, defined as impaired clot formation, is common in intensive care units (ICUs). Many physiological derangements lead to dysfunctional hemostasis in the ICU; most of these are acquired rather than congenital. Coagulopathies in the ICU are often related to systemic diseases, autoimmune dysfunction, acute infection, organ dysfunction, therapeutic medications, and/or other medical treatments. A significant complication of coagulopathy in the critically ill is major bleeding, defined as fatal hemorrhage, hemodynamic instability, transfusion requirement, or intracranial hematomas. Coagulopathy in the ICU often poses complex management dilemmas, especially when coagulopathy coexists with a thrombotic state. Coagulopathy associated with intracerebral hemorrhage (ICH) bears directly on neurologic prognosis and functional outcome. There is a paucity of high-quality evidence for the management of coagulopathies in neurocritical care; however, data derived from studies of patients with ICH may inform treatment decisions. This article focuses on acquired conditions such as pharmacological therapies, organ failure, and platelet dysfunction that are often associated with defective clot formation in the ICU that result in or exacerbate ICH.

 
  • References

  • 1 Chakraverty R, Davidson S, Peggs K, Stross P, Garrard C, Littlewood TJ. The incidence and cause of coagulopathies in an intensive care population. Br J Haematol 1996; 93 (2) 460-463
  • 2 Walsh TS, Stanworth SJ, Prescott RJ, Lee RJ, Watson DM, Wyncoll D ; Writing Committee of the Intensive Care Study of Coagulopathy Investigators. Prevalence, management, and outcomes of critically ill patients with prothrombin time prolongation in United Kingdom intensive care units. Crit Care Med 2010; 38 (10) 1939-1946
  • 3 Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med 2014; 370 (9) 847-859
  • 4 Flibotte JJ, Hagan N, O'Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004; 63 (6) 1059-1064
  • 5 Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P, Investigators C ; CHANT Investigators. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008; 39 (11) 2993-2996
  • 6 Béjot Y, Cordonnier C, Durier J, Aboa-Eboulé C, Rouaud O, Giroud M. Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study. Brain 2013; 136 (Pt 2): 658-664
  • 7 Berwaerts J, Webster J. Analysis of risk factors involved in oral-anticoagulant-related intracranial haemorrhages. QJM 2000; 93 (8) 513-521
  • 8 Fogelholm R, Eskola K, Kiminkinen T, Kunnamo I. Anticoagulant treatment as a risk factor for primary intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 1992; 55 (12) 1121-1124
  • 9 Rådberg JA, Olsson JE, Rådberg CT. Prognostic parameters in spontaneous intracerebral hematomas with special reference to anticoagulant treatment. Stroke 1991; 22 (5) 571-576
  • 10 Brouwers HB, Chang Y, Falcone GJ , et al. Predicting hematoma expansion after primary intracerebral hemorrhage. JAMA Neurol 2014; 71 (2) 158-164
  • 11 Franke CL, de Jonge J, van Swieten JC, Op de Coul AA, van Gijn J. Intracerebral hematomas during anticoagulant treatment. Stroke 1990; 21 (5) 726-730
  • 12 Kase CS, Robinson RK, Stein RW , et al. Anticoagulant-related intracerebral hemorrhage. Neurology 1985; 35 (7) 943-948
  • 13 Brott T, Broderick J, Kothari R , et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997; 28 (1) 1-5
  • 14 Juvela S. Risk factors for impaired outcome after spontaneous intracerebral hemorrhage. Arch Neurol 1995; 52 (12) 1193-1200
  • 15 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 (8) 880-884
  • 16 Flaherty ML, Kissela B, Woo D , et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68 (2) 116-121
  • 17 Cannegieter SC, Rosendaal FR, Briët E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 1994; 89 (2) 635-641
  • 18 Chesebro JH, Fuster V. Optimal antithrombotic therapy for mechanical prosthetic heart valves. Circulation 1996; 94 (9) 2055-2056
  • 19 Fihn SD, McDonell M, Martin D , et al; Warfarin Optimized Outpatient Follow-up Study Group. Risk factors for complications of chronic anticoagulation. A multicenter study. Ann Intern Med 1993; 118 (7) 511-520
  • 20 Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005; 36 (7) 1588-1593
  • 21 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 (5) 553-558
  • 22 Palareti G, Leali N, Coccheri S , et al; Italian Study on Complications of Oral Anticoagulant Therapy. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet 1996; 348 (9025) 423-428
  • 23 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 (8) 524-529
  • 24 van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briët E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993; 153 (13) 1557-1562
  • 25 Fang MC, Go AS, Chang Y , et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007; 120 (8) 700-705
  • 26 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 (10) 745-752
  • 27 Eckman MH, Rosand J, Knudsen KA, Singer DE, Greenberg SM. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke 2003; 34 (7) 1710-1716
  • 28 Neau JP, Couderq C, Ingrand P, Blanchon P, Gil R, Group VGPS ; VGP Study Group. Intracranial hemorrhage and oral anticoagulant treatment. Cerebrovasc Dis 2001; 11 (3) 195-200
  • 29 Punthakee X, Doobay J, Anand SS. Oral-anticoagulant-related intracerebral hemorrhage. Thromb Res 2002; 108 (1) 31-36
  • 30 Sjöblom L, Hårdemark HG, Lindgren A , et al. Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study. Stroke 2001; 32 (11) 2567-2574
  • 31 Hylek EM. Complications of oral anticoagulant therapy: bleeding and nonbleeding, rates and risk factors. Semin Vasc Med 2003; 3 (3) 271-278
  • 32 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 2006; 37 (6) 1465-1470
  • 33 Fredriksson K, Norrving B, Strömblad LG. Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke 1992; 23 (7) 972-977
  • 34 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 2005; 59 (5) 1131-1137 , discussion 1137–1139
  • 35 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 (8) 824-836
  • 36 Hanger HC, Geddes JA, Wilkinson TJ, Lee M, Baker AE. Warfarin-related intracerebral haemorrhage: better outcomes when reversal includes prothrombin complex concentrates. Intern Med J 2013; 43 (3) 308-316
  • 37 Broderick J, Connolly S, Feldmann E , et al; American Heart Association; American Stroke Association Stroke Council; High Blood Pressure Research Council; Quality of Care and Outcomes in Research Interdisciplinary Working Group. 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 (6) 2001-2023
  • 38 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 (1) 145-149
  • 39 Whitling AM, Bussey HI, Lyons RM. Comparing different routes and doses of phytonadione for reversing excessive anticoagulation. Arch Intern Med 1998; 158 (19) 2136-2140
  • 40 Nee R, Doppenschmidt D, Donovan DJ, Andrews TC. Intravenous versus subcutaneous vitamin K1 in reversing excessive oral anticoagulation. Am J Cardiol 1999; 83 (2) 286-288 , A6–A7
  • 41 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 (1) 25-30
  • 42 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 (6) 643-648
  • 43 Butler AC, Tait RC. Management of oral anticoagulant-induced intracranial haemorrhage. Blood Rev 1998; 12 (1) 35-44
  • 44 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 (22) 2721-2724
  • 45 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 (4) 400-406
  • 46 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 (7–8) 869-875
  • 47 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 2006; 37 (1) 151-155
  • 48 Ilyas C, Beyer GM, Dutton RP, Scalea TM, Hess JR. Recombinant factor VIIa for warfarin-associated intracranial bleeding. J Clin Anesth 2008; 20 (4) 276-279
  • 49 Lee SB, Manno EM, Layton KF, Wijdicks EF. Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP. Neurology 2006; 67 (7) 1272-1274
  • 50 Parry-Jones AR, Di Napoli M, Goldstein JN , et al. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage. Ann Neurol 2015; 78 (1) 54-62
  • 51 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 Neurosurgery 2014; 51 (1) 110-115
  • 52 Sarode R, Milling Jr TJ, 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 (11) 1234-1243
  • 53 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 (3) 491-497
  • 54 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 (4) 662-672
  • 55 Brody DL, Aiyagari V, Shackleford AM, Diringer MN. Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage. Neurocrit Care 2005; 2 (3) 263-267
  • 56 Cervera A, Amaro S, Chamorro A. Oral anticoagulant-associated intracerebral hemorrhage. J Neurol 2012; 259 (2) 212-224
  • 57 Hanley JP. Warfarin reversal. J Clin Pathol 2004; 57 (11) 1132-1139
  • 58 Bechtel BF, Nunez TC, Lyon JA, Cotton BA, Barrett TW. Treatments for reversing warfarin anticoagulation in patients with acute intracranial hemorrhage: a structured literature review. Int J Emerg Med 2011; 4 (1) 40
  • 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 (3) 397-406
  • 60 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 (2) 233-239
  • 61 Dowlatshahi D, Butcher KS, Asdaghi N , et al; Canadian PCC Registry (CanPro) Investigators. Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke 2012; 43 (7) 1812-1817
  • 62 Vigué B, Ract C, Tremey B , et al. Ultra-rapid management of oral anticoagulant therapy-related surgical intracranial hemorrhage. Intensive Care Med 2007; 33 (4) 721-725
  • 63 Safaoui MN, Aazami R, Hotz H, Wilson MT, Margulies DR. A promising new alternative for the rapid reversal of warfarin coagulopathy in traumatic intracranial hemorrhage. Am J Surg 2009; 197 (6) 785-790
  • 64 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 (6) 770-774
  • 65 Cartmill M, Dolan G, Byrne JL, Byrne PO. Prothrombin complex concentrate for oral anticoagulant reversal in neurosurgical emergencies. Br J Neurosurg 2000; 14 (5) 458-461
  • 66 Imberti D, Barillari G, Biasioli C , et al. Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage. Blood Transfus 2011; 9 (2) 148-155
  • 67 Imberti D, Barillari G, Biasioli C , et al. Prothrombin complex concentrates for urgent anticoagulation reversal in patients with intracranial haemorrhage. Pathophysiol Haemost Thromb 2008; 36 (5) 259-265
  • 68 Lankiewicz MW, Hays J, Friedman KD, Tinkoff G, Blatt PM. Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost 2006; 4 (5) 967-970
  • 69 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 (2 Suppl): e152S-184S
  • 70 Morgenstern LB, Hemphill III JC, Anderson C , et al; American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41 (9) 2108-2129
  • 71 Dentali F, Marchesi C, Giorgi Pierfranceschi M , et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost 2011; 106 (3) 429-438
  • 72 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 (12) 1495-1500
  • 73 Mayer SA, Brun NC, Begtrup K , et al; FAST Trial Investigators. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008; 358 (20) 2127-2137
  • 74 Mayer SA, Brun NC, Broderick J , et al; United States NovoSeven ICH Trial Investigators. Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA trial. Neurocrit Care 2006; 4 (3) 206-214
  • 75 Illanes S, Zhou W, Schwarting S, Heiland S, Veltkamp R. Comparative effectiveness of hemostatic therapy in experimental warfarin-associated intracerebral hemorrhage. Stroke 2011; 42 (1) 191-195
  • 76 Hemphill III JC, Greenberg SM, Anderson CS , et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46 (7) 2032-2060
  • 77 Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol 2012; 110 (3) 453-460
  • 78 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 2012; 43 (6) 1511-1517
  • 79 Caldeira D, Rodrigues FB, Barra M , et al. Non-vitamin K antagonist oral anticoagulants and major bleeding-related fatality in patients with atrial fibrillation and venous thromboembolism: a systematic review and meta-analysis. Heart 2015; 101 (15) 1204-1211
  • 80 van Ryn J, Stangier J, Haertter S , et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103 (6) 1116-1127
  • 81 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 (14) 1573-1579
  • 82 Siegal DM, Cuker A. Reversal of novel oral anticoagulants in patients with major bleeding. J Thromb Thrombolysis 2013; 35 (3) 391-398
  • 83 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; [Epub ahead of print]
  • 84 Jauch EC, Pineda JA , Claude Hemphill J. Emergency neurological life support: intracerebral hemorrhage. Neurocrit Care 2015; 23 (Suppl. 02) 83-93
  • 85 Stangier J, Rathgen K, Stähle 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 (4) 259-268
  • 86 Pollack Jr CV, Reilly PA, Eikelboom J , et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015; 373 (6) 511-520
  • 87 Patel MR, Mahaffey KW, Garg J , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
  • 88 Hylek EM, Held C, Alexander JH , et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol 2014; 63 (20) 2141-2147
  • 89 Perzborn E, Gruber A, Tinel H , et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost 2013; 110 (1) 162-172
  • 90 Ansell JE. Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants. J Thromb Thrombolysis 2016; 41 (2) 248-252
  • 91 Siegal DM, Curnutte JT, Connolly SJ , et al. Andexanet alfa for the reversal of Factor Xa inhibitor activity. N Engl J Med 2015; 373 (25) 2413-2424
  • 92 Ansell JE, Bakhru SH, Laulicht BE , et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014; 371 (22) 2141-2142
  • 93 Schulman S, Beyth RJ, Kearon C, Levine MN. Physicians ACoC. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 Suppl): 257S-298S
  • 94 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 (2) 181-188
  • 95 Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 1999; 130 (10) 800-809
  • 96 International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet 1997; 349 (9065) 1569-1581
  • 97 Hoffmann P, Keller F. Increased major bleeding risk in patients with kidney dysfunction receiving enoxaparin: a meta-analysis. Eur J Clin Pharmacol 2012; 68 (5) 757-765
  • 98 Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3, Suppl): 188S-203S
  • 99 Hu Q, Brady JO. Recombinant activated factor VII for treatment of enoxaparin-induced bleeding. Mayo Clin Proc 2004; 79 (6) 827
  • 100 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 (8) 582-589
  • 101 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 (2) 350-355
  • 102 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 (5) 796-798
  • 103 He J, Whelton PK, Vu B, Klag MJ. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA 1998; 280 (22) 1930-1935
  • 104 Committee CS ; CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348 (9038) 1329-1339
  • 105 Wiviott SD, Braunwald E, McCabe CH , et al; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357 (20) 2001-2015
  • 106 Becker RC, Bassand JP, Budaj A , et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2011; 32 (23) 2933-2944
  • 107 Bhatt DL, Lincoff AM, Gibson CM , et al; CHAMPION PLATFORM Investigators. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009; 361 (24) 2330-2341
  • 108 Harrington RA, Stone GW, McNulty S , et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009; 361 (24) 2318-2329
  • 109 Connolly S, Pogue J, Hart R , et al; ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367 (9526) 1903-1912
  • 110 Carlson SE, Aldrich MS, Greenberg HS, Topol EJ. Intracerebral hemorrhage complicating intravenous tissue plasminogen activator treatment. Arch Neurol 1988; 45 (10) 1070-1073
  • 111 Jauch EC, Saver JL, Adams Jr HP , et al; American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology. 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 (3) 870-947
  • 112 Moreau D, Timsit JF, Vesin A , et al. Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays. Chest 2007; 131 (6) 1735-1741
  • 113 Nijsten MW, ten Duis HJ, Zijlstra JG , et al. Blunted rise in platelet count in critically ill patients is associated with worse outcome. Crit Care Med 2000; 28 (12) 3843-3846
  • 114 Bonfiglio MF, Traeger SM, Kier KL, Martin BR, Hulisz DT, Verbeck SR. Thrombocytopenia in intensive care patients: a comprehensive analysis of risk factors in 314 patients. Ann Pharmacother 1995; 29 (9) 835-842
  • 115 Shalansky SJ, Verma AK, Levine M, Spinelli JJ, Dodek PM. Risk markers for thrombocytopenia in critically ill patients: a prospective analysis. Pharmacotherapy 2002; 22 (7) 803-813
  • 116 Napolitano LM, Warkentin TE, Almahameed A, Nasraway SA. Heparin-induced thrombocytopenia in the critical care setting: diagnosis and management. Crit Care Med 2006; 34 (12) 2898-2911
  • 117 Visentin GP, Liu CY. Drug-induced thrombocytopenia. Hematol Oncol Clin North Am 2007; 21 (4) 685-696 , vi vi
  • 118 Mavrommatis AC, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med 2000; 28 (2) 451-457
  • 119 Shander A. Anemia in the critically ill. Crit Care Clin 2004; 20 (2) 159-178
  • 120 Carey PJ. Drug-induced myelosuppression: diagnosis and management. Drug Saf 2003; 26 (10) 691-706
  • 121 Curtis BR, Kaliszewski J, Marques MB , et al. Immune-mediated thrombocytopenia resulting from sensitivity to oxaliplatin. Am J Hematol 2006; 81 (3) 193-198
  • 122 Hanes SD, Quarles DA, Boucher BA. Incidence and risk factors of thrombocytopenia in critically ill trauma patients. Ann Pharmacother 1997; 31 (3) 285-289
  • 123 Pedersen-Bjergaard U, Andersen M, Hansen PB. Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs. Eur J Clin Pharmacol 1998; 54 (9–10) 701-706
  • 124 Pedersen-Bjergaard U, Andersen M, Hansen PB. Drug-induced thrombocytopenia: clinical data on 309 cases and the effect of corticosteroid therapy. Eur J Clin Pharmacol 1997; 52 (3) 183-189
  • 125 Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med 2006; 355 (8) 809-817
  • 126 Llevadot J, Coulter SA, Giugliano RP. A practical approach to the diagnosis and management of thrombocytopenia associated with glycoprotein IIb/IIIa receptor inhibitors. J Thromb Thrombolysis 2000; 9 (2) 175-180
  • 127 Warkentin TE. Drug-induced immune-mediated thrombocytopenia—from purpura to thrombosis. N Engl J Med 2007; 356 (9) 891-893
  • 128 Chan KH, Mann KS, Chan TK. The significance of thrombocytopenia in the development of postoperative intracranial hematoma. J Neurosurg 1989; 71 (1) 38-41
  • 129 Slichter SJ. Evidence-based platelet transfusion guidelines. Hematology (Am Soc Hematol Educ Program) 2007; 172-178
  • 130 Levi M, Dörffler-Melly J, Reitsma P , et al. Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C-deficient mice. Blood 2003; 101 (12) 4823-4827
  • 131 Schwartzman RJ, Hill JB. Neurologic complications of disseminated intravascular coagulation. Neurology 1982; 32 (8) 791-797
  • 132 Wijdicks EF, Scott JP. Stroke in the medical intensive-care unit. Mayo Clin Proc 1998; 73 (7) 642-646
  • 133 Voves C, Wuillemin WA, Zeerleder S. International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients. Blood Coagul Fibrinolysis 2006; 17 (6) 445-451
  • 134 Angstwurm MW, Dempfle CE, Spannagl M. New disseminated intravascular coagulation score: a useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores. Crit Care Med 2006; 34 (2) 314-320 , quiz 328
  • 135 Baglin T. Disseminated intravascular coagulation: diagnosis and treatment. BMJ 1996; 312 (7032) 683-687
  • 136 Levi M, Toh CH, Thachil J, Watson HG ; British Committee for Standards in Haematology. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br J Haematol 2009; 145 (1) 24-33
  • 137 Gando S, Nanzaki S, Kemmotsu O. Coagulofibrinolytic changes after isolated head injury are not different from those in trauma patients without head injury. J Trauma 1999; 46 (6) 1070-1076 , discussion 1076–1077
  • 138 Selladurai BM, Vickneswaran M, Duraisamy S, Atan M. Coagulopathy in acute head injury—a study of its role as a prognostic indicator. Br J Neurosurg 1997; 11 (5) 398-404
  • 139 Sawada Y, Sadamitsu D, Sakamoto T, Ikemura K, Yoshioka T, Sugimoto T. Lack of correlation between delayed traumatic intracerebral haematoma and disseminated intravascular coagulation. J Neurol Neurosurg Psychiatry 1984; 47 (10) 1125-1127
  • 140 Touho H, Hirakawa K, Hino A, Karasawa J, Ohno Y. Relationship between abnormalities of coagulation and fibrinolysis and postoperative intracranial hemorrhage in head injury. Neurosurgery 1986; 19 (4) 523-531
  • 141 Cortiana M, Zagara G, Fava S, Seveso M. Coagulation abnormalities in patients with head injury. J Neurosurg Sci 1986; 30 (3) 133-138
  • 142 Olson JD, Kaufman HH, Moake J , et al. The incidence and significance of hemostatic abnormalities in patients with head injuries. Neurosurgery 1989; 24 (6) 825-832
  • 143 Sørensen JV, Jensen HP, Rahr HB , et al. Haemostatic activation in patients with head injury with and without simultaneous multiple trauma. Scand J Clin Lab Invest 1993; 53 (7) 659-665
  • 144 Bredbacka S, Edner G. Soluble fibrin and D-dimer as detectors of hypercoagulability in patients with isolated brain trauma. J Neurosurg Anesthesiol 1994; 6 (2) 75-82
  • 145 Stein SC, Chen XH, Sinson GP, Smith DH. Intravascular coagulation: a major secondary insult in nonfatal traumatic brain injury. J Neurosurg 2002; 97 (6) 1373-1377
  • 146 Piek J, Chesnut RM, Marshall LF , et al. Extracranial complications of severe head injury. J Neurosurg 1992; 77 (6) 901-907
  • 147 Scherer RU, Spangenberg P. Procoagulant activity in patients with isolated severe head trauma. Crit Care Med 1998; 26 (1) 149-156
  • 148 Talving P, Benfield R, Hadjizacharia P, Inaba K, Chan LS, Demetriades D. Coagulopathy in severe traumatic brain injury: a prospective study. J Trauma 2009; 66 (1) 55-61 , discussion 61–62
  • 149 Harhangi BS, Kompanje EJ, Leebeek FW, Maas AI. Coagulation disorders after traumatic brain injury. Acta Neurochir (Wien) 2008; 150 (2) 165-175 , discussion 175
  • 150 Laroche M, Kutcher ME, Huang MC, Cohen MJ, Manley GT. Coagulopathy after traumatic brain injury. Neurosurgery 2012; 70 (6) 1334-1345
  • 151 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134 (5) 1087-1097
  • 152 Eddleston M, de la Torre JC, Oldstone MB, Loskutoff DJ, Edgington TS, Mackman N. Astrocytes are the primary source of tissue factor in the murine central nervous system. A role for astrocytes in cerebral hemostasis. J Clin Invest 1993; 92 (1) 349-358
  • 153 Pathak A, Dutta S, Marwaha N, Singh D, Varma N, Mathuriya SN. Change in tissue thromboplastin content of brain following trauma. Neurol India 2005; 53 (2) 178-182
  • 154 Morel N, Morel O, Petit L , et al. Generation of procoagulant microparticles in cerebrospinal fluid and peripheral blood after traumatic brain injury. J Trauma 2008; 64 (3) 698-704
  • 155 Kumar MA. Coagulopathy associated with traumatic brain injury. Curr Neurol Neurosci Rep 2013; 13 (11) 391
  • 156 Nekludov M, Bellander BM, Blombäck M, Wallen HN. Platelet dysfunction in patients with severe traumatic brain injury. J Neurotrauma 2007; 24 (11) 1699-1706
  • 157 Cohen MJ, Brohi K, Ganter MT, Manley GT, Mackersie RC, Pittet JF. Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway. J Trauma 2007; 63 (6) 1254-1261 , discussion 1261–1262
  • 158 Shakur H, Roberts I, Bautista R , et al; CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376 (9734) 23-32
  • 159 CRASH-2 Collaborators, Intracranial Bleeding Study. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ 2011; 343: d3795
  • 160 Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, Thinkamrop B, Phuenpathom N, Lumbiganon P. Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emerg Med 2013; 13: 20
  • 161 Kluger Y, Riou B, Rossaint R , et al. Safety of rFVIIa in hemodynamically unstable polytrauma patients with traumatic brain injury: post hoc analysis of 30 patients from a prospective, randomized, placebo-controlled, double-blind clinical trial. Crit Care 2007; 11 (4) R85
  • 162 Narayan RK, Maas AI, Marshall LF, Servadei F, Skolnick BE, Tillinger MN ; rFVIIa Traumatic ICH Study Group. Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial. Neurosurgery 2008; 62 (4) 776-786 , discussion 786–788
  • 163 Joseph B, Hadjizacharia P, Aziz H , et al. Prothrombin complex concentrate: an effective therapy in reversing the coagulopathy of traumatic brain injury. J Trauma Acute Care Surg 2013; 74 (1) 248-253
  • 164 Jeger V, Zimmermann H, Exadaktylos AK. Can RapidTEG accelerate the search for coagulopathies in the patient with multiple injuries?. J Trauma 2009; 66 (4) 1253-1257
  • 165 Walsh M, Thomas SG, Howard JC , et al. Blood component therapy in trauma guided with the utilization of the perfusionist and thromboelastography. J Extra Corpor Technol 2011; 43 (3) 162-167
  • 166 Lisman T, Leebeek FW. Hemostatic alterations in liver disease: a review on pathophysiology, clinical consequences, and treatment. Dig Surg 2007; 24 (4) 250-258
  • 167 Tripodi A, Salerno F, Chantarangkul V , et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41 (3) 553-558
  • 168 Stravitz RT, Lisman T, Luketic VA , et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol 2012; 56 (1) 129-136
  • 169 Stravitz RT, Bowling R, Bradford RL , et al. Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure. Hepatology 2013; 58 (1) 304-313
  • 170 Habib M, Roberts LN, Patel RK, Wendon J, Bernal W, Arya R. Evidence of rebalanced coagulation in acute liver injury and acute liver failure as measured by thrombin generation. Liver Int 2014; 34 (5) 672-678
  • 171 Vaquero J, Fontana RJ, Larson AM , et al. Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transpl 2005; 11 (12) 1581-1589
  • 172 Blei AT, Olafsson S, Webster S, Levy R. Complications of intracranial pressure monitoring in fulminant hepatic failure. Lancet 1993; 341 (8838) 157-158
  • 173 Krisl JC, Meadows HE, Greenberg CS, Mazur JE. Clinical usefulness of recombinant activated factor VII in patients with liver failure undergoing invasive procedures. Ann Pharmacother 2011; 45 (11) 1433-1438
  • 174 Meadows HB, Krisl JC, Greenberg CS, Mazur JE. The use of activated recombinant factor VII in a patient with fulminant hepatic failure requiring placement of an intracranial pressure monitor. Ann Pharmacother 2011; 45 (11) e60
  • 175 Kamat P, Kunde S, Vos M , et al. Invasive intracranial pressure monitoring is a useful adjunct in the management of severe hepatic encephalopathy associated with pediatric acute liver failure. Pediatr Crit Care Med 2012; 13 (1) e33-e38
  • 176 Shami VM, Caldwell SH, Hespenheide EE, Arseneau KO, Bickston SJ, Macik BG. Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl 2003; 9 (2) 138-143
  • 177 Dickneite G. Prothrombin complex concentrate versus recombinant factor VIIa for reversal of coumarin anticoagulation. Thromb Res 2007; 119 (5) 643-651
  • 178 Kitchens CS. To bleed or not to bleed? Is that the question for the PTT?. J Thromb Haemost 2005; 3 (12) 2607-2611
  • 179 Segal JB, Dzik WH ; Transfusion Medicine/Hemostasis Clinical Trials Network. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005; 45 (9) 1413-1425
  • 180 Davis JW, Davis IC, Bennink LD , et al. Placement of intracranial pressure monitors: are “normal” coagulation parameters necessary?. J Trauma 2004; 57 (6) 1173-1177
  • 181 Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 2006; 46 (8) 1279-1285
  • 182 Rabiner SF. Bleeding in uremia. Med Clin North Am 1972; 56 (1) 221-233
  • 183 Hedges SJ, Dehoney SB, Hooper JS, Amanzadeh J, Busti AJ. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol 2007; 3 (3) 138-153
  • 184 Remuzzi G. Bleeding in renal failure. Lancet 1988; 1 (8596) 1205-1208
  • 185 Pavord S, Myers B. Bleeding and thrombotic complications of kidney disease. Blood Rev 2011; 25 (6) 271-278
  • 186 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 (1) 8-12
  • 187 Köhler M, Hellstern P, Tarrach H, Bambauer R, Wenzel E, Jutzler GA. Subcutaneous injection of desmopressin (DDAVP): evaluation of a new, more concentrated preparation. Haemostasis 1989; 19 (1) 38-44
  • 188 Zhu J, Guo WM, Yao YY , et al. Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents. Leukemia 1999; 13 (7) 1062-1070
  • 189 Kwaan HC, Cull EH. The coagulopathy in acute promyelocytic leukaemia—what have we learned in the past twenty years. Best Pract Res Clin Haematol 2014; 27 (1) 11-18
  • 190 O'Connell PA, Madureira PA, Berman JN, Liwski RS, Waisman DM. Regulation of S100A10 by the PML-RAR-α oncoprotein. Blood 2011; 117 (15) 4095-4105
  • 191 Kwaan HC, Wang J, Weiss I. Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin. J Thromb Haemost 2004; 2 (2) 306-312