Skip to main content

Advertisement

Log in

Treatment of Coagulopathy in Intracranial Hemorrhage

  • Critical Care Neurology
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

Intracranial hemorrhage (ICH) complicated by coagulopathy is a medical emergency, which can delay neurosurgical intervention, lead to larger hematoma size, and increase mortality until the coagulopathy is corrected. Prompt recognition of coagulopathy during ICH is essential for correct, rapid treatment to reduce ongoing bleeding and improve survival. The proper treatment of a coagulopathic ICH patient is centered on rapid identification of the coagulopathic defect and correction of the underlying coagulopathy to stop acute bleeding. Patients with coagulopathic ICH require admission to a neuro-intensive unit care with management of airway, oxygenation, and systemic arterial and cerebral perfusion pressure; optimization of serum glucose; aggressive treatment of fever; and rehabilitation. Once the coagulopathic defect is reversed, some patients benefit from emergent neurosurgical intervention to prevent secondary brain injury from raised intracranial pressure, hydrocephalus, or mass effect. The management of ICH patients prescribed common antithrombotics such as aspirin, clopidogrel, warfarin, or heparin, as well as thrombolytic agents such as tissue plasminogen activator, is the focus of this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Anderson CS, Chakera TM, Stewart-Wynne EG, Jamrozik KD: Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989–90: incidence and outcome. J Neurol Neurosurg Psychiatry 1994, 57:936–940.

    Article  PubMed  CAS  Google Scholar 

  2. Broderick JP, Brott T, Tomsick T, et al.: Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 1993, 78:188–191.

    Article  PubMed  CAS  Google Scholar 

  3. Counsell C, Boonyakarnkul S, Dennis M, et al.: Primary intracerebral haemorrhage in the Oxfordshire community stroke project, 2: prognosis. Cerebrovasc Dis 1995, 5:26–34.

    Article  Google Scholar 

  4. Brott T, Broderick J, Kothari R, et al.: Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997, 28:1–5.

    PubMed  CAS  Google Scholar 

  5. Broderick JP, Brott TG, Duldner JE, et al.: Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 1993, 24:987–993.

    PubMed  CAS  Google Scholar 

  6. Hart RG, Tonarelli SB, Pearce LA: Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005, 36:1588–1593.

    Article  PubMed  Google Scholar 

  7. Toyoda K, Yasaka M, Nagata K, et al.: Antithrombotic therapy influences location, enlargement, and mortality from intracerebral hemorrhage. The Bleeding with Antithrombotic Therapy (BAT) Retrospective Study. Cerebrovasc Dis 2009, 27:151–159.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Freeman WD, Calvo P, Aduen JF, et al.: Recombinant factor VIIa for warfarin-related ICH: 50 patients [abstract 014]. Presented at the 4th Annual Meeting of the Neurocritical Care Society. Baltimore, MD; November 5, 2006.

  10. Hart RG, Boop BS, Anderson DC: Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke 1995, 26:1471–1477.

    PubMed  CAS  Google Scholar 

  11. 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, 141:745–752.

    PubMed  Google Scholar 

  12. Flaherty ML, Haverbusch M, Sekar P, et al.: Long-term mortality after intracerebral hemorrhage. Neurology 2006, 66:1182–1186.

    Article  PubMed  CAS  Google Scholar 

  13. Sjoblom 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.

    Article  PubMed  CAS  Google Scholar 

  14. Cucchiara B, Messe S, Sansing L, et al.: Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008, 39:2993–2996.

    Article  PubMed  CAS  Google Scholar 

  15. Flaherty ML, Tao H, Haverbusch M, et al.: Warfarin use leads to larger intracerebral hematomas. Neurology 2008, 71:1084–1089.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Flaherty ML, Kissela B, Woo D, et al.: The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007, 68:116–121.

    Article  PubMed  CAS  Google Scholar 

  18. Falk RH: Atrial fibrillation. N Engl J Med 2001, 344:1067–1078.

    Article  PubMed  CAS  Google Scholar 

  19. Aguilar MI, Hart RG, Kase CS, et al.: Treatment of warfarin- associated intracerebral hemorrhage: literature review and expert opinion. Mayo Clin Proc 2007, 82:82–92.

    Article  PubMed  CAS  Google Scholar 

  20. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. N Engl J Med 1990, 323:1505–1511.

  21. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet 1993, 342:1255–1262.

  22. Hart RG, Halperin JL, Pearce LA, et al.: Lessons from the stroke prevention in atrial fibrillation trials. Ann Intern Med 2003, 138:831–838.

    PubMed  Google Scholar 

  23. Hart RG, Pearce LA, Aguilar MI: Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007, 146:857–867.

    PubMed  Google Scholar 

  24. Smith NL, Psaty BM, Furberg CD, et al.: Temporal trends in the use of anticoagulants among older adults with atrial fibrillation. Arch Intern Med 1999, 159:1574–1578.

    Article  PubMed  CAS  Google Scholar 

  25. Schulman S, Beyth RJ, Kearon C, et al.: Hemorrhagic complications of anticoagulant and thrombolytic treatment: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:257S–298S.

    Article  PubMed  CAS  Google Scholar 

  26. Hylek EM, Evans-Molina C, Shea C, et al.: Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007, 115:2689–2696.

    Article  PubMed  CAS  Google Scholar 

  27. Goldstein LB, Simel DL: Is this patient having a stroke? JAMA 2005, 293:2391–2402.

    Article  PubMed  CAS  Google Scholar 

  28. 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, 38:2001–2023.

    Article  PubMed  Google Scholar 

  29. Ecker RD, Wijdicks EF: Footprints of coagulopathy. J Neurol Neurosurg Psychiatry 2002, 73:534.

    Article  PubMed  CAS  Google Scholar 

  30. Ichikawa K, Yanagihara C: Sedimentation level in acute intracerebral hematoma in a patient receiving anticoagulation therapy: an autopsy study. Neuroradiology 1998, 40:380–382.

    Article  PubMed  CAS  Google Scholar 

  31. Laissy JP, Normand G, Monroc M, et al.: Spontaneous intracerebral hematomas from vascular causes. Predictive value of CT compared with angiography. Neuroradiology 1991, 33:291–295.

    Article  PubMed  CAS  Google Scholar 

  32. Berwaerts J, Robb OJ, Jeffers TA, Webster J: Intracerebral haemorrhages and oral anticoagulation in the north of Scotland. Scott Med J 2000, 45:101–104.

    PubMed  CAS  Google Scholar 

  33. Yasaka M, Oomura M, Ikeno K, et al.: Effect of prothrombin complex concentrate on INR and blood coagulation system in emergency patients treated with warfarin overdose. Ann Hematol 2003, 82:121–123.

    PubMed  CAS  Google Scholar 

  34. Flibotte JJ, Hagan N, O’Donnell J, et al.: Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004, 63:1059–1064.

    PubMed  CAS  Google Scholar 

  35. Yasaka M, Minematsu K, Naritomi H, et al.: Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin. Thromb Haemost 2003, 89:278–283.

    PubMed  CAS  Google Scholar 

  36. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996, 348:633–638.

  37. ESPRIT: Oral anticoagulation in patients after cerebral ischemia of arterial origin and risk of intracranial hemorrhage. Stroke 2003, 34:e45–e46.

  38. Gullov AL, Koefoed BG, Petersen P: Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation. Arch Intern Med 1999, 159:1322–1328.

    Article  PubMed  CAS  Google Scholar 

  39. Yamaguchi T: Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation: a multicenter, prospective, randomized trial. Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study Group. Stroke 2000, 31:817–821.

    PubMed  CAS  Google Scholar 

  40. Freeman WD, Aguilar MI: Management of warfarin-related intracerebral hemorrhage. Expert Rev Neurother 2008, 8(2):271–290.

    Article  PubMed  CAS  Google Scholar 

  41. Flaherty ML, Adeoye O, Sekar P, et al.: The challenge of designing a treatment trial for warfarin-associated intracerebral hemorrhage. Stroke 2009, 40:1738–1742.

    Article  PubMed  CAS  Google Scholar 

  42. Stafford DW: The vitamin K cycle. J Thromb Haemost 2005, 3:1873–1878.

    Article  PubMed  CAS  Google Scholar 

  43. Ansell J, Hirsh J, Dalen J, et al.: Managing oral anticoagulant therapy. Chest 2001, 119:22S–38S.

    Article  PubMed  CAS  Google Scholar 

  44. Fredriksson K, Norrving B, Stromblad LG: Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke 1992, 23:972–977.

    PubMed  CAS  Google Scholar 

  45. 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.

    Article  PubMed  Google Scholar 

  46. Lacy CF, Armstrong LL, Goldman MP, Lance LL: Drug Information Handbook, edn 11. Hudson, OH: Lexi-Comp, Inc.; 2003.

    Google Scholar 

  47. Riegert-Johnson DL, Volcheck GW: The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review. Ann Allergy Asthma Immunol 2002, 89:400–406.

    Article  PubMed  CAS  Google Scholar 

  48. Fiore LD, Scola MA, Cantillon CE, Brophy MT: Anaphylactoid reactions to vitamin K. J Thromb Thrombolysis 2001, 11:175–183.

    Article  PubMed  CAS  Google Scholar 

  49. 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, 37:151–155.

    Article  PubMed  Google Scholar 

  50. Lee SB, Manno EM, Layton KF, Wijdicks EF: Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP. Neurology 2006, 67:1272–1274.

    Article  PubMed  CAS  Google Scholar 

  51. Schulman S: Clinical practice. Care of patients receiving long-term anticoagulant therapy. N Engl J Med 2003, 349:675–683.

    Article  PubMed  Google Scholar 

  52. 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.

    PubMed  CAS  Google Scholar 

  53. Mayer SA, Brun NC, Begtrup K, et al.: Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005, 352:777–785.

    Article  PubMed  CAS  Google Scholar 

  54. 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, 358:2127–2137.

    Article  PubMed  CAS  Google Scholar 

  55. Deveras RA, Kessler CM: Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Ann Intern Med 2002, 137:884–888.

    PubMed  CAS  Google Scholar 

  56. 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.

    Article  PubMed  CAS  Google Scholar 

  57. Earnshaw SR, Joshi AV, Wilson MR, Rosand J: Cost-effectiveness of recombinant activated factor VII in the treatment of intracerebral hemorrhage. Stroke 2006, 37:2751–2758.

    Article  PubMed  Google Scholar 

  58. Ardelt AA, Arenberg S, Kulesza P, Streiff MB: Anticoagulation reversal in patients with intracerebral hemorrhage, a survey of Neurocritical Care Society members [abstract 053]. Abstracts from the 4th Annual Meeting of the Neurocritical Care Society. Baltimore, MD; 2006:240.

  59. Hellstern P: Production and composition of prothrombin complex concentrates: correlation between composition and therapeutic efficiency. Thromb Res 1999, 95:S7–S12.

    Article  PubMed  CAS  Google Scholar 

  60. Hellstern P, Halbmayer WM, Kohler M, et al.: Prothrombin complex concentrates: indications, contraindications, and risks: a task force summary. Thromb Res 1999, 95:S3–S6.

    Article  PubMed  CAS  Google Scholar 

  61. 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, 333:1581–1587.

  62. Derex L, Hermier M, Adeleine P, et al.: Clinical and imaging predictors of intracerebral haemorrhage in stroke patients treated with intravenous tissue plasminogen activator. J Neurol Neurosurg Psychiatry 2005, 76:70–75.

    Article  PubMed  CAS  Google Scholar 

  63. Demchuk AM, Morgenstern LB, Krieger DW, et al.: Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke 1999, 30:34–39.

    PubMed  CAS  Google Scholar 

  64. Gebel JM, Brott TG, Sila CA, et al.: Decreased perihematomal edema in thrombolysis-related intracerebral hemorrhage compared with spontaneous intracerebral hemorrhage. Stroke 2000, 31:596–600.

    PubMed  CAS  Google Scholar 

  65. Mahaffey KW, Granger CB, Sloan MA, et al.: Neurosurgical evacuation of intracranial hemorrhage after thrombolytic therapy for acute myocardial infarction: experience from the GUSTO-I trial. Global Utilization of Streptokinase and Tissue-plasminogen activator (tPA) for Occluded Coronary Arteries. Am Heart J 1999, 138:493–499.

    Article  PubMed  CAS  Google Scholar 

  66. Hanger HC, Fletcher VJ, Wilkinson TJ, et al.: Effect of aspirin and warfarin on early survival after intracerebral haemorrhage. J Neurol 2008, 255:347–352.

    Article  PubMed  CAS  Google Scholar 

  67. Creutzfeldt CJ, Weinstein JR, Longstreth WT Jr, et al.: Prior antiplatelet therapy, platelet infusion therapy, and outcome after intracerebral hemorrhage. J Stroke Cerebrovasc Dis 2009, 18:221–228.

    Article  PubMed  Google Scholar 

  68. 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, 40:2398–2401.

    Article  PubMed  Google Scholar 

  69. Naidech AM, Bendok BR, Garg RK, et al.: Reduced platelet activity is associated with more intraventricular hemorrhage. Neurosurgery 2009, 65:684–688.

    Article  PubMed  Google Scholar 

  70. Naidech AM, Bassin SL, Bernstein RA, et al.: Reduced platelet activity is more common than reported anti-platelet medication use in patients with intracerebral hemorrhage. Neurocrit Care 2009, 11:307–310.

    Article  CAS  Google Scholar 

  71. Kobrinsky NL, Israels ED, Gerrard JM, et al.: Shortening of bleeding time by 1-deamino-8-D-arginine vasopressin in various bleeding disorders. Lancet 1984, 1:1145–1148.

    Article  PubMed  CAS  Google Scholar 

  72. Demaerschalk BM, Aguilar MI: Treatment of acute intracerebral hemorrhage. Curr Treat Options Neurol 2008, 10:455–467.

    Article  PubMed  Google Scholar 

  73. Steiner T, Diringer MN, Schneider D, et al.: Dynamics of intraventricular hemorrhage in patients with spontaneous intracerebral hemorrhage: risk factors, clinical impact, and effect of hemostatic therapy with recombinant activated factor VII. Neurosurgery 2006, 59:767–773, discussion 773–774.

    Article  PubMed  Google Scholar 

  74. Sugg RM, Gonzales NR, Matherne DE, et al.: Myocardial injury in patients with intracerebral hemorrhage treated with recombinant factor VIIa. Neurology 2006, 67:1053–1055.

    Article  PubMed  CAS  Google Scholar 

  75. Fernandes HM, Gregson B, Siddique S, Mendelow AD: Surgery in intracerebral hemorrhage. The uncertainty continues. Stroke 2000, 31:2511–2516.

    PubMed  CAS  Google Scholar 

  76. Mendelow AD, Gregson BA, Fernandes HM, et al.: Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematoma s in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005, 365:387–397.

    PubMed  Google Scholar 

  77. Duncan PW, Zorowitz R, Bates B, et al.: Management of adult stroke rehabilitation care: a clinical practice guideline. Stroke 2005, 36:e100–e143.

    Article  PubMed  Google Scholar 

  78. Schulman S, Bijsterveld NR: Anticoagulants and their reversal. Transfus Med Rev 2007, 21(1):37–48.

    Article  PubMed  Google Scholar 

  79. Aiyagaru V: Correction of coagulopathy secondary to oral and parenteral anticoagulants. Continuum 2009, 15(3):138–157.

    Google Scholar 

  80. Mathews M, Newman R, Chappell ET: Management of coagulopathy in the setting of acute neurosurgical disease and injury. Neurocrit Care 2006, 5(2):141–152.

    Article  PubMed  CAS  Google Scholar 

  81. Mannucci PM, Vicente V, Vianello L, et al.: Controlled trial of desmopressin (DDAVP) in the treatment of conditions associated with prolonged bleeding time. Blood 1986, 67:1148–1153.

    PubMed  CAS  Google Scholar 

  82. Hillbom ME, Huhtakangas JT: Platelet transfusion in acute intracerebral hemorrhage. NCT 00699621. Available at ClinicalTrials.gov.

  83. Kobinsky NL, Gergard JM, Watson CM, et al.: Shortening of bleeding time by 1-deamino-8-D-arginine vasopressin in various bleeding disorders. Lancet 1984, 323:1145–1148.

    Article  Google Scholar 

Download references

Acknowledgment

The authors thank Tejal Patel, MD, Mayo Clinic Hematology Consultant, for her careful review of Tables 2 and 3 and clarification of hematologic tests.

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria I. Aguilar MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aguilar, M.I., Freeman, W.D. Treatment of Coagulopathy in Intracranial Hemorrhage. Curr Treat Options Neurol 12, 113–128 (2010). https://doi.org/10.1007/s11940-010-0061-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-010-0061-1

Keywords

Navigation