Skip to main content Accessibility help
  • Print publication year: 2009
  • Online publication date: May 2010

Chapter 5 - Coagulopathy-related intracerebral hemorrhage


1.Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillations. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154: 1449–1457.
2. Broderick JP, Brott T, Tomsick T, Huster G, Miller R. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med 1992; 326: 733–736.
3. Qureshi AI, Saad M, Zaidat OO, et al. Intracerebral hemorrhages associated with neurointerventional procedures using a combination of antithrombotic agents including abciximab. Stroke 2002; 33: 1916–1919.
4. Cannegieter SC, Rosendaal FR, Wintzen AR, et al. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11–17.
5. 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: 511–520.
6. 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: 423–428.
7. 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: 524–529.
8. 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: 1557–1562.
9. Butler AC, Tait RC. Management of oral anticoagulant-induced intracranial haemorrhage. Blood Rev 1998; 12: 35–44.
10. Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke 1995; 26: 1471–1477.
11. Franke CL, de Jonge J, van Swieten JC, Op de Coul AA, van Gijn J. Intracerebral hematomas during anticoagulant treatment. Stroke 1990; 21: 726–730.
12. 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: 880–884.
13.Bleeding during antithrombotic therapy in patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Arch Intern Med 1996; 156: 409–416.
14. Flibotte JJ, Hagan N, O'Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004; 63: 1059–1064.
15. Vasishta S, Toor F, Johansen A, Hasan M. Stroke prevention in atrial fibrillation: physicians' attitudes to anticoagulation in older people. Arch Gerontol Geriatr 2001; 33: 219–226.
16. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370–2375.
17. Flaherty ML, Haverbusch M, Sekar P, et al. Location and outcome of anticoagulant-associated intracerebral hemorrhage. Neurocrit Care 2006; 5: 197–201.
18. Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68: 116–121.
19. Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997; 28: 1–5.
20. Juvela S. Risk factors for impaired outcome after spontaneous intracerebral hemorrhage. Arch Neurol 1995; 52: 1193–1200.
21. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 1993; 24: 987–993.
22. Nilsson OG, Lindgren A, Brandt L, Saveland H. Prediction of death in patients with primary intracerebral hemorrhage: a prospective study of a defined population. J Neurosurg 2002; 97: 531–536.
23. Kazui S, Minematsu K, Yamamoto H, Sawada T, Yamaguchi T. Predisposing factors to enlargement of spontaneous intracerebral hematoma. Stroke 1997; 28: 2370–2375.
24. Daverat P, Castel JP, Dartigues JF, Orgogozo JM. Death and functional outcome after spontaneous intracerebral hemorrhage. A prospective study of 166 cases using multivariate analysis. Stroke 1991; 22: 1–6.
25. Tuhrim S, Dambrosia JM, Price TR, et al. Prediction of intracerebral hemorrhage survival. Ann Neurol 1988; 24: 258–263.
26. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897–902.
27. Berwaerts J, Dijkhuizen RS, Robb OJ, Webster J. Prediction of functional outcome and in-hospital mortality after admission with oral anticoagulant-related intracerebral hemorrhage. Stroke 2000; 31: 2558–2562.
28. Mathiesen T, Benediktsdottir K, Johnsson H, Lindqvist M, von Holst H. Intracranial traumatic and non-traumatic haemorrhagic complications of warfarin treatment. Acta Neurol Scand 1995; 91: 208–214.
29. Sjöblom L, Hardemark HG, Lindgren A, et al. Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study. Stroke 2001; 32: 2567–2574.
30. 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: 1495–1500.
31. Hart RG. What causes intracerebral hemorrhage during warfarin therapy? Neurology 2000; 55: 907–908.
32. Roob G, Schmidt R, Kapeller P, et al. MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology 1999; 52: 991–994.
33. Revesz T, Ghiso J, Lashley T, et al. Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol 2003; 62: 885–898.
34. Rosand J, Hylek EM, O'Donnell HC, Greenberg SM. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 2000; 55: 947–951.
35. Yasaka M, Minematsu K, Yamaguchi T. Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation. Intern Med 2001; 40: 1183–1188.
36. Gorter JW. Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups. Neurology 1999; 53: 1319–1327.
37.A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. Ann Neurol 1997; 42: 857–865.
38. Makris M, Greaves M, Phillips WS, et al. 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: 477–480.
39. Hirsh J, Dalen J, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001; 119: 8S–21S.
40. Hanley JP. Warfarin reversal. J Clin Pathol 2004; 57: 1132–1139.
41. Hellstern P. Production and composition of prothrombin complex concentrates: correlation between composition and therapeutic efficiency. Thromb Res 1999; 95: S7–12.
42. Rost S, Fregin A, Ivaskevicius V, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 2004; 427: 537–541.
43. Fregin A, Rost S, Wolz W, et al. Homozygosity mapping of a second gene locus for hereditary combined deficiency of vitamin K-dependent clotting factors to the centromeric region of chromosome 16. Blood 2002; 100: 3229–3232.
44. Oldenburg J, von Brederlow B, Fregin A, et al. Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex. Thromb Haemost 2000; 84: 937–941.
45. O'Donnell HC, Rosand J, Knudsen KA, et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med 2000; 342: 240–245.
46. Mendelow AD, Gregson BA, Fernandes HM, et al.; STICH investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral hematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005; 365 (9457): 387–397.
47. Lipton RB, Berger AR, Lesser ML, Lantos G, Portenoy RK. Lobar vs thalamic and basal ganglion hemorrhage: clinical and radiographic features. J Neurol 1987; 234: 86–90.
48. Fujii Y, Tanaka R, Takeuchi S, et al. Hematoma enlargement in spontaneous intracerebral hemorrhage. J Neurosurg 1994; 80: 51–57.
49. Gebel JM, Sila CA, Sloan MA, et al. Thrombolysis-related intracranial hemorrhage: a radiographic analysis of 244 cases from the GUSTO-1 trial with clinical correlation. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. Stroke 1998; 29: 563–569.
50. Huttner HB, Steiner T, Hartmann M, et al. Comparison of ABC/2 estimation technique to computer-assisted planimetric analysis in warfarin related intracerebral parenchymal hemorrhage. Stroke 2006; 47: 404–408.
51. Kothari RU, Brott T, Broderick JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996; 27: 1304–1305.
52. Kwak R, Kadoya S, Suzuki T. Factors affecting the prognosis in thalamic hemorrhage. Stroke 1983; 14: 493–500.
53. Gebel JM, Sila CA, Sloan MA, et al. Comparison of the ABC/2 estimation technique to computer-assisted volumetric analysis of intraparenchymal and subdural hematomas complicating the GUSTO-1 trial. Stroke 1998; 29: 1799–1801.
54. Becker KJ, Baxter AB, Cohen WA, et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology 2001; 56: 766–772.
55. Becker KJ, Baxter AB, Bybee HM, et al. Extravasation of radiographic contrast is an independent predictor of death in primary intracerebral hemorrhage. Stroke 1999; 30: 2025–2032.
56. Yasaka M, Minematsu K, Naritomi H, Sakata T, Yamaguchi T. Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin. Thromb Haemost 2003; 89: 278–283.
57. Fogelholm R, Eskola K, Kiminkinen T, Kunnamo I. Anticoagulant treatment as a risk factor for primary intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 1992; 55: 1121–1124.
58. Radberg JA, Olsson JE, Radberg CT. Prognostic parameters in spontaneous intracerebral hematomas with special reference to anticoagulant treatment. Stroke 1991; 22: 571–576.
59. Mayer SA. Ultra-early hemostatic therapy for intracerebral hemorrhage. Stroke 2003; 34: 224–229.
60. Sansing LH, Kaznatcheeva EA, Perkins CJ, et al. Edema after intracerebral hemorrhage: correlations with coagulation parameters and treatment. J Neurosurg 2003; 98: 985–992.
61. Schellinger PD, Fiebach JB, Hoffmann K, et al. Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra? Stroke 2003; 34: 1674–1679.
62. Mayer SA, Brun NC, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005; 352: 777–785.
63. Ansell J, Hirsh J, Dalen J, et al. Managing oral anticoagulant therapy. Chest 2001; 119: 22S–38S.
64. Boulis NM, Bobek MP, Schmaier A, Hoff JT. Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery 1999; 45: 1113–1118; discussion 1118–1119.
65. Erhardtsen E, Nony P, Dechavanne M, et al. The effect of recombinant factor VIIa (NovoSeven) in healthy volunteers receiving acenocoumarol to an International Normalized Ratio above 2.0. Blood Coagul Fibrinolysis 1998; 9: 741–748.
66. Deveras RA, Kessler CM. Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Ann Intern Med 2002; 137: 884–888.
67. Baglin TP, Keeling DM, Watson HG. Guidelines on oral anticoagulation (warfarin): third edition–2005 update. Br J Haematol 2006; 132: 277–285.
68. Broderick JP, Connolly ES, Feldman E, et al.; American Heart Association/American Stroke Association Stroke Council; American Heart Association/American Stroke Association 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): 2001–23. Epub2007 May 3.
69. Steiner T, Kaste M, Forsting M, et al. Recommendations for the management of intracranial haemorrhage – part I: spontaneous intracerebral haemorrhage. The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee. Cerebrovasc Dis 2006; 22(4): 294–316. Epub 2006 Jul 28. Erratum in: Cerebrovasc Dis 2006; 22 (5–6): 461. Katse Markku [corrected to Kaste, Markku].
70. Pindur G, Morsdorf S, Schenk JF, et al. The overdosed patient and bleedings with oral anticoagulation. Semin Thromb Hemost 1999; 25: 85–88.
71. Hellstern P, Muntean W, Schramm W, Seifried E, Solheim BG. Practical guidelines for the clinical use of plasma. Thromb Res 2002; 107 Suppl 1: S53–57.
72. Gilstad CW. Anaphylactic transfusion reactions. Curr Opin Hematol 2003; 10: 419–423.
73. Pomper GJ, Wu Y, Snyder EL. Risks of transfusion-transmitted infections: 2003. Curr Opin Hematol 2003; 10: 412–418.
74. Hellstern P, Halbmayer WM, Kohler M, Seitz R, Muller-Berghaus G. Prothrombin complex concentrates: indications, contraindications, and risks: a task force summary. Thromb Res 1999; 95: S3–6.
75. Fredriksson K, Norrving B, Stromblad LG. Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke 1992; 23: 972–977.
76. Seitz R, Dodt J. Virus safety of prothrombin complex concentrates and factor IX concentrates. Thromb Res 1999; 95: S19–23.
77. Sorensen B, Johansen P, Nielsen GL, Sorensen JC, Ingerslev J. Reversal of the International Normalized Ratio with recombinant activated factor VII in central nervous system bleeding during warfarin thromboprophylaxis: clinical and biochemical aspects. Blood Coagul Fibrinolysis 2003; 14: 469–477.
78. Brody DL, Aiyagari V, Shackleford AM, Diringer MN. Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage. Neurocrit Care 2005; 2: 263–267.
79. Boffard KD, Riou B, Warren B, et al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. J Trauma 2005; 59: 8–15; discussion 15–18.
80. Mayer SA, Brun NC, Broderick J, et al. Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage. Stroke 2005; 36: 74–79.
81. Baker RI, Coughlin PB, Gallus AS, et al. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Hemostasis. Med J Aust 2004; 181: 492–497.
82. Wijdicks EF, Schievink WI, Brown RD, Mullany CJ. The dilemma of discontinuation of anticoagulation therapy for patients with intracranial hemorrhage and mechanical heart valves. Neurosurgery 1998; 42: 769–773.
83. Phan TG, Koh M, Wijdicks EF. Safety of discontinuation of anticoagulation in patients with intracranial hemorrhage at high thromboembolic risk. Arch Neurol 2000; 57: 1710–1713.
84. Ananthasubramaniam K, Beattie JN, Rosman HS, Jayam V, Borzak S. How safely and for how long can warfarin therapy be withheld in prosthetic heart valve patients hospitalized with a major hemorrhage? Chest 2001; 119: 478–484.
85. Bertram M, Bonsanto M, Hacke W, Schwab S. Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation. J Neurol 2000; 247: 209–214.
86. Leira R, Davalos A, Silva Y, et al. Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology 2004; 63: 461–467.
87. Phan TG, Koh M, Vierkant RA, Wijdicks EF. Hydrocephalus is a determinant of early mortality in putaminal hemorrhage. Stroke 2000; 31: 2157–2162.
88. Albers GW, Diener HC, Frison L, et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005; 293: 690–698.
89. Fiessinger JN, Huisman MV, Davidson BL, et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA 2005; 293: 681–689.
90. Sorensen B, Johansen P, Christiansen K, Woelke M, Ingerslev J. Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation. J Thromb Haemost 2003; 1: 551–558.
91. Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost 2005; 3: 1843–1853.
92. Bates SM, Weitz JI. New anticoagulants: beyond heparin, low-molecular-weight heparin and warfarin. Br J Pharmacol 2005; 144: 1017–1028.
93. Bates SM, Weitz JI. Coagulation assays. Circulation 2005; 112: e 53–60.
94. Gibaldi M, Wittkowsky AK. Contemporary use of and future roles for heparin in antithrombotic therapy. J Clin Pharmacol 1995; 35: 1031–1045.
95. Sloan MA, Price TR, Petito CK, et al. Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and heparin therapy for acute myocardial infarction: the Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial combined experience. Neurology 1995; 45: 649–658.
96. Schmulling S, Rudolf J, Strotmann-Tack T, et al. Acetylsalicylic acid pretreatment, concomitant heparin therapy and the risk of early intracranial hemorrhage following systemic thrombolysis for acute ischemic stroke. Cerebrovasc Dis 2003; 16: 183–190.
97. Boeer A, Voth E, Henze T, Prange HW. Early heparin therapy in patients with spontaneous intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 1991; 54: 466–467.
98. Kase CS, Furlan AJ, Wechsler LR, et al. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial. Neurology 2001; 57: 1603–1610.
99. Tanne D, Kasner SE, Demchuk AM, et al. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Circulation 2002; 105: 1679–1685.
100. Selim M, Fink JN, Kumar S, et al. Predictors of hemorrhagic transformation after intravenous recombinant tissue plasminogen activator: prognostic value of the initial apparent diffusion coefficient and diffusion-weighted lesion volume. Stroke 2002; 33: 2047–2052.
101. Lapchak PA, Chapman DF, Zivin JA. Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thromboembolic stroke. Stroke 2000; 31: 3034–3040.