| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Neurology (Drs. Rosand and Greenberg, and H.C. O’Donnell) and Medicine (Dr. Hylek), Massachusetts General Hospital and Harvard Medical School, Boston.
Address correspondence and reprint requests to Dr. S.M. Greenberg, Massachusetts General Hospital, Wang ACC 836, Boston, MA 02114; e-mail: greenberg{at}helix.mgh.harvard.edu
BACKGROUND: Intracerebral hemorrhage (ICH) is the most feared complication of warfarin therapy. The pathogenesis of this often-fatal complication remains obscure. Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar hemorrhage in the elderly and is associated with specific alleles of the APOE gene.
OBJECTIVE: To assess the role of CAA in warfarin-associated ICH.
METHODS: Clinical characteristics and APOE genotype were compared between 41 patients with warfarin-related ICH (from a cohort of 59 consecutive patients aged 
65 years with supratentorial ICH on warfarin) and 66 randomly selected individuals aged 65 years without ICH taking warfarin. In addition, all neuropathologic specimens from ICH patients were reviewed for the presence and severity of CAA.
RESULTS: Hemorrhages tended to be in the lobar regions of the brain, and most (76%) occurred with an international normalized ratio of 
3.0. The APOE 
2 allele was overrepresented among patients with warfarin-associated lobar hemorrhage (allele frequency 0.13 versus 0.04 in control subjects; p = 0.031). After controlling for other variables associated with ICH, carriers of the 2 allele had an OR of 3.8 (95% CI, 1.0 to 14.6) for lobar ICH. CAA was pathologically diagnosed as the cause of lobar hemorrhage in 7 of 11 patients with available tissue samples.
CONCLUSIONS: CAA is an important cause of warfarin-associated lobar ICH in the elderly. Although diagnosis of CAA before hemorrhage is not yet possible, these data offer hope that future patients at high risk for hemorrhage may be identified before initiation of warfarin therapy.
This article has been cited by other articles:
|
|
 |
|
  O. Jolobe Risk factors for anticoagulation-related bleeding complications QJM, May 1, 2008; 101(5): 419 - 419. [Full Text] [PDF]
|
|
|
|
 |
|
 R. O. Hopkins, L. K. Weaver, K. J. Valentine, C. Mower, S. Churchill, and J. Carlquist Apolipoprotein E Genotype and Response of Carbon Monoxide Poisoning to Hyperbaric Oxygen Treatment Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 1001 - 1006. [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. 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]
|
|
|
|
|
|
E. M. Hylek, C. Evans-Molina, C. Shea, L. E. Henault, and S. Regan Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation Circulation, May 29, 2007; 115(21): 2689 - 2696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Thanvi and T. Robinson Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people Age Ageing, November 1, 2006; 35(6): 565 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Chao, A. L. Kotsenas, and D. F. Broderick Cerebral Amyloid Angiopathy: CT and MR Imaging Findings RadioGraphics, September 1, 2006; 26(5): 1517 - 1531. [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]
|
|
|
|
|
|
G. G. Leblanc, J. F. Meschia, D. T. Stuss, and V. Hachinski Genetics of Vascular Cognitive Impairment: The Opportunity and the Challenges Stroke, January 1, 2006; 37(1): 248 - 255. [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]
|
|
|
|
|
|
J. Rosand Editorial Comment--Epistasis Is Coming: Are We Ready? Stroke, September 1, 2005; 36(9): 1879 - 1880. [Full Text] [PDF]
|
|
|
|
|
|
D. Woo, R. Kaushal, R. Chakraborty, J. Woo, M. Haverbusch, P. Sekar, B. Kissela, A. Pancioli, E. Jauch, D. Kleindorfer, et al. Association of Apolipoprotein E4 and Haplotypes of the Apolipoprotein E Gene With Lobar Intracerebral Hemorrhage Stroke, September 1, 2005; 36(9): 1874 - 1879. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 T Hamaguchi, S Okino, N Sodeyama, Y Itoh, A Takahashi, E Otomo, M Matsushita, H Mizusawa, and M Yamada Association of a polymorphism of the transforming growth factor-{beta}1 gene with cerebral amyloid angiopathy J. Neurol. Neurosurg. Psychiatry, May 1, 2005; 76(5): 696 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Ritter, D. W. Droste, K. Hegedus, R. Szepesi, D. G. Nabavi, L. Csiba, and E. B. Ringelstein Role of cerebral amyloid angiopathy in intracerebral hemorrhage in hypertensive patients Neurology, April 12, 2005; 64(7): 1233 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Fang, Y. Chang, E. M. Hylek, J. Rosand, S. M. Greenberg, A. S. Go, and D. E. Singer Advanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for Atrial Fibrillation Ann Intern Med, November 16, 2004; 141(10): 745 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J P Hanley Warfarin reversal J. Clin. Pathol., November 1, 2004; 57(11): 1132 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jeerakathil, P. A. Wolf, A. Beiser, J. K. Hald, R. Au, C. S. Kase, J. M. Massaro, and C. DeCarli Cerebral Microbleeds: Prevalence and Associations With Cardiovascular Risk Factors in the Framingham Study Stroke, August 1, 2004; 35(8): 1831 - 1835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rosand, M. H. Eckman, K. A. Knudsen, D. E. Singer, and S. M. Greenberg The Effect of Warfarin and Intensity of Anticoagulation on Outcome of Intracerebral Hemorrhage Arch Intern Med, April 26, 2004; 164(8): 880 - 884. [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]
|
|
|
|
|
|
K.S. Wong, Y.L. Chan, J.Y. Liu, S. Gao, and W. W.M. Lam Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral hemorrhages Neurology, February 11, 2003; 60(3): 511 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
July 23 Highlights Neurology, July 23, 2002; 59(2): 153 - 155. [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]
|
|
|
|
 |
|
 J.-t. Guo, J. Yu, D. Grass, F. C. de Beer, and M. S. Kindy Inflammation-Dependent Cerebral Deposition of Serum Amyloid A Protein in a Mouse Model of Amyloidosis J. Neurosci., July 15, 2002; 22(14): 5900 - 5909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Coutts, R. Frayne, R. Sevick, and A. Demchuk Microbleeding on MRI as a Marker for Hemorrhage After Stroke Thrombolysis Stroke, June 1, 2002; 33(6): 1457 - 1458. [Full Text] [PDF]
|
|
|
|
 |
|
 O M P Jolobe Chronic subdural haematoma in the elderly J R Soc Med, January 8, 2002; 95(8): 427 - 428. [Full Text] [PDF]
|
|
|
|
|
|
R. G. Hart and J. L. Halperin Atrial Fibrillation and Stroke : Concepts and Controversies Stroke, March 1, 2001; 32(3): 803 - 808. [Full Text] [PDF]
|
|
|
|
 |
|
 Warfarin-Related ICH and Cerebral Amyloid Angiopathy Journal Watch Neurology, January 4, 2001; 2001(104): 5 - 5. [Full Text]
|
|
|
|
|
|
R. G. Hart What causes intracerebral hemorrhage during warfarin therapy? Neurology, October 10, 2000; 55(7): 907 - 908. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
