| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 1995;26:1471-1477.)
© 1995 American Heart Association, Inc.
Articles |
Oral Anticoagulants and Intracranial Hemorrhage
Facts and Hypotheses
From the Department of Medicine (Neurology), University of Texas Health Science Center, San Antonio (R.G.H., B.S.B.), and the Department of Neurology, University of Minnesota, Minneapolis (D.C.A.).
Background Intracranial hemorrhage is the most feared and lethal complication of oral anticoagulation. We review the frequency, predictors, and prognosis of this most common neurological complication of oral anticoagulation.
Summary of Review Anticoagulation to conventional intensities increases the risk of intracranial hemorrhage 7- to 10-fold, to an absolute rate of nearly 1%/y for many stroke-prone patients. Most (70%) anticoagulant-related intracranial hemorrhages are intracerebral hematomas (approximately 60% are fatal); the bulk of the remainder are subdural hematomas. Predictors of anticoagulant-related intracerebral hematoma are advanced patient age, prior ischemic stroke, hypertension, and intensity of anticoagulation. In approximately half of anticoagulated patients with intracerebral hematoma the bleeding evolves slowly over 12 to 24 hours, and emergency reversal of anticoagulation is crucial.
Conclusions Both patient factors and anticoagulation intensity importantly influence the rate of anticoagulation-related intracranial hemorrhage. Patient-related risk factors for this complication overlap with those for ischemic stroke. The risk/benefit equation of anticoagulation for elderly, stroke-prone patients is complex and differs from that for younger patients. The absolute rate reduction (not the relative risk reduction) of ischemic stroke by anticoagulation is the critical issue and must offset accentuation of often lethal brain hemorrhage.
Key Words: anticoagulants • cerebral hemorrhage • intracerebral hemorrhage
This article has been cited by other articles:
 |
|
 |
|
  M. H. Eckman, J. Rosand, S. M. Greenberg, and B. F. Gage Cost-Effectiveness of Using Pharmacogenetic Information in Warfarin Dosing for Patients With Nonvalvular Atrial Fibrillation Ann Intern Med, January 20, 2009; 150(2): 73 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Eckman, L. K.S. Wong, Y. O.Y. Soo, W. Lam, S. R. Yang, S. M. Greenberg, and J. Rosand Patient-Specific Decision-Making for Warfarin Therapy in Nonvalvular Atrial Fibrillation: How Will Screening With Genetics and Imaging Help? * Supplemental Appendix Stroke, December 1, 2008; 39(12): 3308 - 3315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. Claassen, N. Kazemi, A. Y. Zubkov, E. F. M. Wijdicks, and A. A. Rabinstein Restarting Anticoagulation Therapy After Warfarin-Associated Intracerebral Hemorrhage Arch Neurol, October 1, 2008; 65(10): 1313 - 1318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Fric-Shamji, M. F. Shamji, J. Cole, and B. G. Benoit Modifiable risk factors for intracerebral hemorrhage: Study of anticoagulated patients Can Fam Physician, August 1, 2008; 54(8): 1138 - 1139.e4. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Dentali and M. A. Crowther Management of Excessive Anticoagulant Effect Due to Vitamin K Antagonists Hematology, January 1, 2008; 2008(1): 266 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Nutescu ASHP Therapeutic Position Statement on Antithrombotic Therapy in Chronic Atrial Fibrillation Am. J. Health Syst. Pharm., November 1, 2007; 64(21): 2281 - 2291. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Broderick, S. Connolly, E. Feldmann, D. Hanley, C. Kase, D. Krieger, M. Mayberg, L. Morgenstern, C. S. Ogilvy, P. Vespa, et al. REPRINT: 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: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, October 16, 2007; 116(16): e391 - e413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Broderick, S. Connolly, E. Feldmann, D. Hanley, C. Kase, D. Krieger, M. Mayberg, L. Morgenstern, C. S. Ogilvy, P. Vespa, 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: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke, June 1, 2007; 38(6): 2001 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Aguilar, R. G. Hart, C. S. Kase, W. D. Freeman, B. J. Hoeben, R. C. Garcia, J. E. Ansell, S. A. Mayer, B. Norrving, J. Rosand, et al. Treatment of Warfarin-Associated Intracerebral Hemorrhage: Literature Review and Expert Opinion Mayo Clin. Proc., January 1, 2007; 82(1): 82 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dawson and M. Walters New and emerging treatments for stroke Br. Med. Bull., November 7, 2006; (2006) ldl011v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Lee, E. M. Manno, K. F. Layton, and E. F.M. Wijdicks Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP. Neurology, October 10, 2006; 67(7): 1272 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. B. Huttner, P. D. Schellinger, M. Hartmann, M. Kohrmann, E. Juettler, J. Wikner, S. Mueller, U. Meyding-Lamade, R. Strobl, U. Mansmann, 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, June 1, 2006; 37(6): 1465 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. Koennecke Cerebral microbleeds on MRI: Prevalence, associations, and potential clinical implications Neurology, January 24, 2006; 66(2): 165 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Saloheimo, M. Ahonen, S. Juvela, J. Pyhtinen, E.-R. Savolainen, and M. Hillbom Regular Aspirin-Use Preceding the Onset of Primary Intracerebral Hemorrhage is an Independent Predictor for Death Stroke, January 1, 2006; 37(1): 129 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Steiner, J. Rosand, and M. Diringer Intracerebral Hemorrhage Associated With Oral Anticoagulant Therapy: Current Practices and Unresolved Questions Stroke, January 1, 2006; 37(1): 256 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G. Butchart, C. Gohlke-Barwolf, M. J. Antunes, P. Tornos, R. De Caterina, B. Cormier, B. Prendergast, B. Iung, H. Bjornstad, C. Leport, et al. Recommendations for the management of patients after heart valve surgery Eur. Heart J., November 2, 2005; 26(22): 2463 - 2471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wani, E. Nga, and R. Navaratnasingham Should a patient with primary intracerebral haemorrhage receive antiplatelet or anticoagulant therapy? BMJ, August 20, 2005; 331(7514): 439 - 442. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Guly, L. Jones, and T. Nokes Trauma in the anticoagulated patient Trauma, July 1, 2005; 7(3): 155 - 161. [Abstract] [PDF]
|
|
|
|
|
|
R. G. Hart, S. B. Tonarelli, and L. A. Pearce Avoiding Central Nervous System Bleeding During Antithrombotic Therapy: Recent Data and Ideas Stroke, July 1, 2005; 36(7): 1588 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Passero, B. Calchetti, and S. Bartalini Intracranial Bleeding in Patients With Vertebrobasilar Dolichoectasia Stroke, July 1, 2005; 36(7): 1421 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Chimowitz, M. J. Lynn, H. Howlett-Smith, B. J. Stern, V. S. Hertzberg, M. R. Frankel, S. R. Levine, S. Chaturvedi, S. E. Kasner, C. G. Benesch, et al. Comparison of Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis N. Engl. J. Med., March 31, 2005; 352(13): 1305 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Manno, J. L. D. Atkinson, J. R. Fulgham, and E. F. M. Wijdicks Emerging Medical and Surgical Management Strategies in the Evaluation and Treatment of Intracerebral Hemorrhage Mayo Clin. Proc., March 1, 2005; 80(3): 420 - 433. [Abstract] [PDF]
|
|
|
|
 |
|
 M. F. Scholten, A. S. Thornton, J. M. Mekel, P. J. Koudstaal, and L. J. Jordaens Anticoagulation in atrial fibrillation and flutter Europace, January 1, 2005; 7(5): 492 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J P Hanley Warfarin reversal J. Clin. Pathol., November 1, 2004; 57(11): 1132 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Mehta, P. S. Mueller, H. L. Gonzalez-Arriaza, V. S. Pankratz, and T. A. Rummans Safety of Electroconvulsive Therapy in Patients Receiving Long-term Warfarin Therapy Mayo Clin. Proc., November 1, 2004; 79(11): 1396 - 1401. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A. Smythe, W. E. Dager, and N. M. Patel Managing Complications of Anticoagulant Therapy Journal of Pharmacy Practice, October 1, 2004; 17(5): 327 - 346. [Abstract] [PDF]
|
|
|
|
|
|
J. J. Flibotte, N. Hagan, J. O'Donnell, S. M. Greenberg, and J. Rosand Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage Neurology, September 28, 2004; 63(6): 1059 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 483S - 512S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Walker, D. F. Broderick, A. L. Kotsenas, and F. A. Rubino Routine Use of Gradient-Echo MRI to Screen for Cerebral Amyloid Angiopathy in Elderly Patients Am. J. Roentgenol., June 1, 2004; 182(6): 1547 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Rockson and G. W. Albers Comparing the guidelines: anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation J. Am. Coll. Cardiol., March 17, 2004; 43(6): 929 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Stollberger, J. Finsterer, M. H. Eckman, J. Rosand, K. A. Knudsen, S. M. Greenberg, and D. E. Singer Antithrombotic Therapy After Cerebral Hemorrhages * Response Stroke, November 1, 2003; 34 (11): e217 - e218. [Full Text] [PDF]
|
|
|
|
 |
|
 S. J.-A. Wilson, P. S. Wells, M. J. Kovacs, G. M. Lewis, J. Martin, E. Burton, and D. R. Anderson Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial Can. Med. Assoc. J., August 19, 2003; 169(4): 293 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Packard, C. S. Kase, A. S. Aly, and G. D. Barest "Computed Tomography-Negative" Intracerebral Hemorrhage: Case Report and Implications for Management Arch Neurol, August 1, 2003; 60(8): 1156 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Eckman, J. Rosand, K. A. Knudsen, D. E. Singer, and S. M. Greenberg Can Patients Be Anticoagulated After Intracerebral Hemorrhage?: A Decision Analysis Stroke, July 1, 2003; 34(7): 1710 - 1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Johnsen, L. Pedersen, S. Friis, W. J. Blot, J. K. McLaughlin, J. H. Olsen, and H. T. Sorensen Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hospitalization for Intracerebral Hemorrhage: A Population-Based Case-Control Study Stroke, February 1, 2003; 34(2): 387 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tsushima, J. Aoki, and K. Endo Brain Microhemorrhages Detected on T2*-Weighted Gradient-Echo MR Images AJNR Am. J. Neuroradiol., January 1, 2003; 24(1): 88 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. I.H. Kwa, J. J. van der Sande, J. Stam, N. Tijmes, and J. L. Vrooland Retinal arterial changes correlate with cerebral small-vessel disease Neurology, November 26, 2002; 59(10): 1536 - 1540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Smith, J. Rosand, K. A. Knudsen, E. M. Hylek, and S. M. Greenberg Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke Neurology, July 23, 2002; 59(2): 193 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Rabinstein, J. L. Atkinson, and E. F.M. Wijdicks Emergency craniotomy in patients worsening due to expanded cerebral hematoma: To what purpose? Neurology, May 14, 2002; 58(9): 1367 - 1372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Woo, L. R. Sauerbeck, B. M. Kissela, J. C. Khoury, J. P. Szaflarski, J. Gebel, R. Shukla, A. M. Pancioli, E. C. Jauch, A. G. Menon, et al. Genetic and Environmental Risk Factors for Intracerebral Hemorrhage: Preliminary Results of a Population-Based Study * Editorial Comment: Preliminary Results of a Population-Based Study Stroke, May 1, 2002; 33(5): 1190 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Man-Son-Hing and A. Laupacis Balancing the Risks of Stroke and Upper Gastrointestinal Tract Bleeding in Older Patients With Atrial Fibrillation Arch Intern Med, March 11, 2002; 162(5): 541 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Kidwell, J. L. Saver, J. P. Villablanca, G. Duckwiler, A. Fredieu, K. Gough, M. C. Leary, S. Starkman, Y. P. Gobin, R. Jahan, et al. Magnetic Resonance Imaging Detection of Microbleeds Before Thrombolysis: An Emerging Application Stroke, January 1, 2002; 33(1): 95 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Torn, MD;, A. Algra, MD;, and F.R. Rosendaal, MD Oral anticoagulation for cerebral ischemia of arterial origin: High initial bleeding risk Neurology, December 11, 2001; 57(11): 1993 - 1999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sjoblom, H.-G. Hardemark, A. Lindgren, B. Norrving, M. Fahlen, M. Samuelsson, L. Stigendal, D. Stockelberg, A. Taghavi, L. Wallrup, et al. Management and Prognostic Features of Intracerebral Hemorrhage During Anticoagulant Therapy: A Swedish Multicenter Study Stroke, November 1, 2001; 32(11): 2567 - 2574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wehinger, C. Stollberger, T. Langer, B. Schneider, and J. Finsterer Evaluation of Risk Factors for Stroke/Embolism and of Complications Due to Anticoagulant Therapy in Atrial Fibrillation Stroke, October 1, 2001; 32(10): 2246 - 2252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. McCarron, J. A.R. Nicoll, M. J. O'Leary, R. J.L. Waugh, A. I. Qureshi, and D. F. Hanley Spontaneous Intracerebral Hemorrhage N. Engl. J. Med., September 6, 2001; 345(10): 769 - 770. [Full Text] [PDF]
|
|
|
|
 |
|
 N Dudley Importance of risk communication and decision making in cardiovascular conditions in older patients: a discussion paper Qual. Saf. Health Care, September 1, 2001; 10(90001): i19 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Castellino, M J Cuadrado, T Godfrey, M A Khamashta, and G R V Hughes Characteristics of patients with antiphospholipid syndrome with major bleeding after oral anticoagulant treatment Ann Rheum Dis, May 1, 2001; 60(5): 527 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Denke Dairy Products and Red Meat : Midwesterners Always Knew They Were Good for Something Circulation, February 13, 2001; 103(6): 784 - 786. [Full Text] [PDF]
|
|
|
|
|
|
G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke Chest, January 1, 2001; 119(1_suppl): 300S - 320S. [Full Text] [PDF]
|
|
|
|
 |
|
 O G Nilsson, A Lindgren, N Stahl, L Brandt, and H Saveland Incidence of intracerebral and subarachnoid haemorrhage in southern Sweden J. Neurol. Neurosurg. Psychiatry, November 1, 2000; 69(5): 601 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Hart What causes intracerebral hemorrhage during warfarin therapy? Neurology, October 10, 2000; 55(7): 907 - 908. [Full Text] [PDF]
|
|
|
|
|
|
J. Rosand, E. M. Hylek, H. C. O'Donnell, and S. M. Greenberg Warfarin-associated hemorrhage and cerebral amyloid angiopathy: A genetic and pathologic study Neurology, October 10, 2000; 55(7): 947 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Crawley, D. Bevan, and D. Wren Management of intracranial bleeding associated with anticoagulation: balancing the risk of further bleeding against thromboembolism from prosthetic heart valves J. Neurol. Neurosurg. Psychiatry, September 1, 2000; 69(3): 396 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Berwaerts and J. Webster Analysis of risk factors involved in oral-anticoagulant-related intracranial haemorrhages QJM, August 1, 2000; 93(8): 513 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Wong, V. Mok, W. W. M. Lam, R. Kay, A. Tang, Y. L. Chan, and J. Woo Aspirin-associated intracerebral hemorrhage: Clinical and radiologic features Neurology, June 27, 2000; 54(12): 2298 - 2301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Palareti, J. Hirsh, C. Legnani, C. Manotti, A. D'Angelo, V. Pengo, M. Moia, G. Guazzaloca, S. Musolesi, and S. Coccheri Oral Anticoagulation Treatment in the Elderly: A Nested, Prospective, Case-Control Study Arch Intern Med, February 28, 2000; 160(4): 470 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Halperin, S. J. Fry, and S. L. Houser Case 37-1999 -- A 72-Year-Old Woman with a Prosthetic Aortic Valve and Intracranial Hemorrhage N. Engl. J. Med., December 9, 1999; 341(24): 1829 - 1835. [Full Text] [PDF]
|
|
|
|
|
|
J. W. Gorter Major bleeding during anticoagulation after cerebral ischemia: Patterns and risk factors Neurology, October 1, 1999; 53(6): 1319 - 1319. [Abstract] [Full Text]
|
|
|
|
|
|
M. Man-Son-Hing, G. Nichol, A. Lau, and A. Laupacis Choosing Antithrombotic Therapy for Elderly Patients With Atrial Fibrillation Who Are at Risk for Falls Arch Intern Med, April 12, 1999; 159(7): 677 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kronmal, R. G. Hart, T.A. Manolio, R.L. Talbert, N.J. Beauchamp, and A. Newman Aspirin Use and Incident Stroke in the Cardiovascular Health Study Stroke, May 1, 1998; 29(5): 887 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aessopos, D. Farmakis, M. Karagiorga, I. Rombos, and D. Loucopoulos Pseudoxanthoma Elasticum Lesions and Cardiac Complications as Contributing Factors for Strokes in ß-Thalassemia Patients Stroke, December 1, 1997; 28(12): 2421 - 2424. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. J. Ackermann Anticoagulant Therapy in Patients Aged 80 Years or More With Atrial Fibrillation: More Caution Is Needed Arch Fam Med, March 1, 1997; 6(2): 105 - 110. [Abstract] [PDF]
|
|