FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 338:1793-1797 June 18, 1998 Number 25 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Idiopathic cerebral-vein thrombosis can cause serious neurologic disability. We evaluated risk factors for this disorder, including genetic risk factors (mutations in the genes encoding factor V and prothrombin) and nongenetic risk factors (such as the use of oral contraceptive agents).

Methods We compared the prevalence of these risk factors in 40 patients with cerebral-vein thrombosis, 80 patients with deep-vein thrombosis of the lower extremities, and 120 healthy controls. The G1691A mutation in the factor V gene and the G20210A prothrombin-gene mutation, which are established genetic risk factors for venous thrombosis, were studied. We also assessed the use of oral contraceptives and other risk factors for thrombosis.

Results The prevalence of the prothrombin-gene mutation was higher in patients with cerebral-vein thrombosis (20 percent) than in healthy controls (3 percent; odds ratio, 10.2; 95 percent confidence interval, 2.3 to 31.0) and was similar to that in patients with deep-vein thrombosis (18 percent). Similar results were obtained for the mutation in the factor V gene. The use of oral contraceptives was more frequent among women with cerebral-vein thrombosis (96 percent) than among controls (32 percent; odds ratio, 22.1; 95 percent confidence interval, 5.9 to 84.2) and among those with deep-vein thrombosis (61 percent; odds ratio, 4.4; 95 percent confidence interval, 1.1 to 17.8). For women who were taking oral contraceptives and who also had the prothrombin-gene mutation (seven patients with cerebral-vein thrombosis but only one control), the odds ratio for cerebral-vein thrombosis rose to 149.3 (95 percent confidence interval, 31.0 to 711.0).

Conclusions Mutations in the prothrombin gene and the factor V gene are associated with cerebral-vein thrombosis. The use of oral contraceptives is also strongly and independently associated with the disorder. The presence of both the prothrombin-gene mutation and oral-contraceptive use raises the risk of cerebral-vein thrombosis further.

Source Information

From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (I.M., E.S., F.D., P.M.M.), Neurology Department (G.L.), and Epidemiology Unit (E.T.), Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Hospital, University of Milan, Milan, Italy.

Address reprint requests to Dr. Martinelli at the Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Via Pace 9, 20122 Milan, Italy.

Full Text of this Article

This article has been cited by other articles:

• Santoro, R. (2009). A Woman With Rectal Sinus and Left Transversal Sinus Thrombosis After Ovarian Stimulation: Case Report. CLIN APPL THROMB HEMOST 15: 711-713 [Abstract]  
• Dangal, G., Thapa, L. B. (2009). Cerebral venous sinus thrombosis presenting in pregnancy and puerperium. BMJ Case Reports 2009: bcr0620092045-bcr0620092045 [Abstract] [Full Text]  
• Coutinho, J. M., Ferro, J. M., Canhao, P., Barinagarrementeria, F., Cantu, C., Bousser, M.-G., Stam, J. (2009). Cerebral Venous and Sinus Thrombosis in Women. Stroke 40: 2356-2361 [Abstract] [Full Text]  
• Martinelli, I., Franchini, M., Mannucci, P. M. (2008). How I treat rare venous thromboses. Blood 112: 4818-4823 [Abstract] [Full Text]  
• Rathbun, S. (2008). Venous thromboembolism in women. Vasc Med 13: 255-266 [Abstract]  
• Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. (2008). Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 630S-669S [Abstract] [Full Text]  
• Wysokinska, E. M., Wysokinski, W. E., Brown, R. D., Karnicki, K., Gosk-Beirska, I., Grill, D., McBane, R. D. II (2008). Thrombophilia differences in cerebral venous sinus and lower extremity deep venous thrombosis. Neurology 70: 627-633 [Abstract] [Full Text]  
• Voetsch, B., Jin, R. C., Bierl, C., Deus-Silva, L., Camargo, E. C.S., Annichino-Bizacchi, J. M., Handy, D. E., Loscalzo, J. (2008). Role of Promoter Polymorphisms in the Plasma Glutathione Peroxidase (GPx-3) Gene as a Risk Factor for Cerebral Venous Thrombosis. Stroke 39: 303-307 [Abstract] [Full Text]  
• Goldstein, L. B., Adams, R., Alberts, M. J., Appel, L. J., Brass, L. M., Bushnell, C. D., Culebras, A., DeGraba, T. J., Gorelick, P. B., Guyton, J. R., Hart, R. G., Howard, G., Kelly-Hayes, M., Nixon, J.V., Sacco, R. L. (2006). Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.. Circulation 113: e873-e923 [Abstract] [Full Text]  
• Goldstein, L. B., Adams, R., Alberts, M. J., Appel, L. J., Brass, L. M., Bushnell, C. D., Culebras, A., DeGraba, T. J., Gorelick, P. B., Guyton, J. R., Hart, R. G., Howard, G., Kelly-Hayes, M., Nixon, J.V., Sacco, R. L. (2006). Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.. Stroke 37: 1583-1633 [Abstract] [Full Text]  
• Morcos, Z., van den Bergh, W. M., van der Schaaf, I., van Gijn, J. (2006). The spectrum of presentations of venous infarction caused by deep cerebral vein thrombosis. Neurology 66: 1284-1284 [Full Text]  
• Bick, R. L. (2006). Hereditary and Acquired Thrombophilic Disorders. CLIN APPL THROMB HEMOST 12: 125-135  
• Dentali, F., Crowther, M., Ageno, W. (2006). Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis. Blood 107: 2766-2773 [Abstract] [Full Text]  
• van den Bergh, W. M., van der Schaaf, I., van Gijn, J. (2005). The spectrum of presentations of venous infarction caused by deep cerebral vein thrombosis. Neurology 65: 192-196 [Abstract] [Full Text]  
• Stam, J. (2005). Thrombosis of the Cerebral Veins and Sinuses. NEJM 352: 1791-1798 [Full Text]  
• Meschia, J. F., Brott, T. G., Brown, R. D. Jr (2005). Genetics of Cerebrovascular Disorders. Mayo Clin Proc. 80: 122-132 [Abstract]  
• Gomes, M. P. V., Deitcher, S. R. (2004). Risk of Venous Thromboembolic Disease Associated With Hormonal Contraceptives and Hormone Replacement Therapy: A Clinical Review. Arch Intern Med 164: 1965-1976 [Abstract] [Full Text]  
• Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. (2004). Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 483S-512S [Abstract] [Full Text]  
• Martinelli, I., Battaglioli, T., Bucciarelli, P., Passamonti, S. M., Mannucci, P. M. (2004). Risk Factors and Recurrence Rate of Primary Deep Vein Thrombosis of the Upper Extremities. Circulation 110: 566-570 [Abstract] [Full Text]  
• Kovalevsky, G., Gracia, C. R., Berlin, J. A., Sammel, M. D., Barnhart, K. T. (2004). Evaluation of the Association Between Hereditary Thrombophilias and Recurrent Pregnancy Loss: A Meta-analysis. Arch Intern Med 164: 558-563 [Abstract] [Full Text]  
• Dunkley, S., Johnston, I. (2004). Thrombophilia as a common predisposing factor in pseudotumor cerebri. Blood 103: 1972-1973 [Full Text]  
• Ou, Y.-C., Kao, Y.-L., Lai, S.-L., Kung, F.-T., Huang, F.-J., Chang, S.-Y., ChangChien, C.-C. (2003). Thromboembolism after ovarian stimulation: successful management of a woman with superior sagittal sinus thrombosis after IVF and embryo transfer: Case report. Hum Reprod 18: 2375-2381 [Abstract] [Full Text]  
• Petitti, D. B. (2003). Combination Estrogen-Progestin Oral Contraceptives. NEJM 349: 1443-1450 [Full Text]  
• Heller, C., Heinecke, A., Junker, R., Knofler, R., Kosch, A., Kurnik, K., Schobess, R., von Eckardstein, A., Strater, R., Zieger, B., Nowak-Gottl, U. (2003). Cerebral Venous Thrombosis in Children: A Multifactorial Origin. Circulation 108: 1362-1367 [Abstract] [Full Text]  
• Martinelli, I., Battaglioli, T., Pedotti, P., Cattaneo, M., Mannucci, P. M. (2003). Hyperhomocysteinemia in cerebral vein thrombosis. Blood 102: 1363-1366 [Abstract] [Full Text]  
• Cosmi, B., Legnani, C., Bernardi, F., Coccheri, S., Palareti, G. (2003). Role of Family History in Identifying Women With Thrombophilia and Higher Risk of Venous Thromboembolism During Oral Contraception. Arch Intern Med 163: 1105-1109 [Abstract] [Full Text]  
• Cakmak, S., Derex, L., Berruyer, M., Nighoghossian, N., Philippeau, F., Adeleine, P., Hermier, M., Froment, J.C., Trouillas, P. (2003). Cerebral venous thrombosis: Clinical outcome and systematic screening of prothrombotic factors. Neurology 60: 1175-1178 [Abstract] [Full Text]  
• Evans, W. E., McLeod, H. L. (2003). Pharmacogenomics -- Drug Disposition, Drug Targets, and Side Effects. NEJM 348: 538-549 [Full Text]  
• Deitcher, S. R, Gomes, M. P. (2003). Hypercoagulable state testing and malignancy screening following venous thromboembolic events. Vasc Med 8: 33-46 [Abstract]  
• Seibert, C., Barbouche, E., Fagan, J., Myint, E., Wetterneck, T., Wittemyer, M. (2003). Prescribing Oral Contraceptives for Women Older Than 35 Years of Age. ANN INTERN MED 138: 54-64 [Abstract] [Full Text]  
• Schafer, A. I., Levine, M. N., Konkle, B. A., Kearon, C. (2003). Thrombotic Disorders: Diagnosis and Treatment. ASH Education Book 2003: 520-539 [Abstract] [Full Text]  
• Bates, S. M., Ginsberg, J. S. (2002). How we manage venous thromboembolism during pregnancy. Blood 100: 3470-3478 [Abstract] [Full Text]  
• Pollak, E. S., Lam, H.-S., Russell, J. E. (2002). The G20210A mutation does not affect the stability of prothrombin mRNA in vivo. Blood 100: 359-362 [Abstract] [Full Text]  
• Thaler, D. E., Frosch, M. P. (2002). Case 16-2002 - A 41-Year-Old Woman with Global Headache and an Intracranial Mass. NEJM 346: 1651-1658 [Full Text]  
• Joffe, H. V, Goldhaber, S. Z (2002). Laboratory thrombophilias and venous thromboembolism. Vasc Med 7: 93-102 [Abstract]  
• Madonna, P., de Stefano, V., Coppola, A., Cirillo, F., Cerbone, A. M., Orefice, G., Di Minno, G. (2002). Hyperhomocysteinemia and Other Inherited Prothrombotic Conditions in Young Adults With a History of Ischemic Stroke. Stroke 33: 51-56 [Abstract] [Full Text]  
• Herrington, D. M., Klein, K. P. (2001). Genome and Hormones: Gender Differences in Physiology: Invited Review: Pharmacogenetics of estrogen replacement therapy. J. Appl. Physiol. 91: 2776-2784 [Abstract] [Full Text]  
• Lynch, J. K., Nelson, K. B., Curry, C. J., Grether, J. K. (2001). Cerebrovascular Disorders in Children With the Factor V Leiden Mutation. J Child Neurol 16: 735-744 [Abstract]  
• Bauer, K. A. (2001). The Thrombophilias: Well-Defined Risk Factors with Uncertain Therapeutic Implications. ANN INTERN MED 135: 367-373 [Abstract] [Full Text]  
• deVeber, G., Andrew, M., Adams, C., Bjornson, B., Booth, F., Buckley, D. J., Camfield, C. S., David, M., Humphreys, P., Langevin, P., MacDonald, E. A., Meaney, B., Shevell, M., Sinclair, D. B., Yager, J., Gillett, J., the Canadian Pediatric Ischemic Stroke Study Group, (2001). Cerebral Sinovenous Thrombosis in Children. NEJM 345: 417-423 [Abstract] [Full Text]  
• KOMAJDA, M., CHARRON, P. (2001). How will the human genome project change cardiovascular medicine?. Heart 86: 123-124 [Full Text]  
• Hankey, G. J., Eikelboom, J. W., van Bockxmeer, F. M., Lofthouse, E., Staples, N., Baker, R. I. (2001). Inherited Thrombophilia in Ischemic Stroke and Its Pathogenic Subtypes. Stroke 32: 1793-1799 [Abstract] [Full Text]  
• Edelberg, J. M., Christie, P. D., Rosenberg, R. D. (2001). Regulation of Vascular Bed-Specific Prothrombotic Potential. Circ. Res. 89: 117-124 [Abstract] [Full Text]  
• CHAK, M, WALLACE, G R, GRAHAM, E M, STANFORD, M R (2001). Thrombophilia: genetic polymorphisms and their association with retinal vascular occlusive disease. Br J Ophthalmol 85: 883-886 [Full Text]  
• Federman, D. G., Kirsner, R. S. (2001). An Update on Hypercoagulable Disorders. Arch Intern Med 161: 1051-1056 [Abstract] [Full Text]  
• Seligsohn, U., Lubetsky, A. (2001). Genetic Susceptibility to Venous Thrombosis. NEJM 344: 1222-1231 [Full Text]  
• Macik, B. G., Rand, J. H., Konkle, B. A. (2001). Thrombophilia: What's a Practitioner to Do?. ASH Education Book 2001: 322-338 [Abstract] [Full Text]  
• Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. (2001). Antithrombotic and Thrombolytic Therapy for Ischemic Stroke. Chest 119 : 300S-320S [Full Text]  
• Holtzman, N. A., Marteau, T. M. (2000). Will Genetics Revolutionize Medicine?. NEJM 343: 141-144 [Full Text]  
• Gillum, L. A., Mamidipudi, S. K., Johnston, S. C. (2000). Ischemic Stroke Risk With Oral Contraceptives: A Meta-analysis. JAMA 284: 72-78 [Abstract] [Full Text]  
• Mira, Y., Aznar, J., Estelles, A., Vaya, A., Villa, P., Ferrando, F. (2000). State-of-the-Art Review : Congenital and Acquired Thrombotic Risk Factors in Women Using Oral Contraceptives: Clinical Aspects. CLIN APPL THROMB HEMOST 6: 162-168 [Abstract]  
• Madonna, P., De Stefano, V., Coppola, A., Albisinni, R., Cerbone, A. M. (2000). G20210A PRTH Gene Mutation and Other Trombophilic Polymorphisms in Patients With Cerebral Vein Thrombosis. Stroke 31 : 1785-1790 [Full Text]  
• Kupferminc, M. J., Yair, D., Bornstein, N. M., Lessing, J. B., Eldor, A. (2000). Transient Focal Neurological Deficits During Pregnancy in Carriers of Inherited Thrombophilia. Stroke 31: 892-895 [Abstract] [Full Text]  
• Lane, D. A., Grant, P. J. (2000). Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 95: 1517-1532 [Full Text]  
• Gerhardt, A., Scharf, R. E., Beckmann, M. W., Struve, S., Bender, H. G., Pillny, M., Sandmann, W., Zotz, R. B. (2000). Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium. NEJM 342: 374-380 [Abstract] [Full Text]  
• Lanthier, S., Carmant, L., David, M., Larbrisseau, A., de Veber, G. (2000). Stroke in children: The coexistence of multiple risk factors predicts poor outcome. Neurology 54: 371-371 [Abstract] [Full Text]  
• Lenfant, C. (1999). Conquering Cardiovascular Disease: Progress and Promise. JAMA 282: 2068-2070 [Full Text]  
• Nowak-Gottl, U., Strater, R., Heinecke, A., Junker, R., Koch, H.-G., Schuierer, G., von Eckardstein, A. (1999). Lipoprotein (a) and Genetic Polymorphisms of Clotting Factor V, Prothrombin, and Methylenetetrahydrofolate Reductase Are Risk Factors of Spontaneous Ischemic Stroke in Childhood. Blood 94: 3678-3682 [Abstract] [Full Text]  
• Gul, A., Aslantas, A. B., Tekinay, T., Konice, M., Ozcelik, T. (1999). Procoagulant mutations and venous thrombosis in Behcet's disease. Rheumatology (Oxford) 38: 1298-1299 [Full Text]  
• Irish, A. (1999). Renal allograft thrombosis: can thrombophilia explain the inexplicable?. Nephrol Dial Transplant 14: 2297-2303 [Full Text]  
• Collins, F. S. (1999). Medical and Societal Consequences of the Human Genome Project. NEJM 341: 28-37 [Full Text]  
• Speroff, L. (1999). Modern Low-Dose Oral Contraceptives Are Very Safe. J. Clin. Endocrinol. Metab. 84: 1823-1825 [Full Text]  
• Rosenberg, R. D., Aird, W. C. (1999). Vascular-Bed-Specific Hemostasis and Hypercoagulable States. NEJM 340: 1555-1564 [Full Text]  
• Kianmanesh Rad, N. A., Helmerhorst, F. M. (1999). OHSS and cerebrovascular thrombosis. Hum Reprod 14: 1138a-1138a [Full Text]  
• Yang, Y., Algazy, K. M. (1999). Warfarin-Induced Skin Necrosis in a Patient with a Mutation of the Prothrombin Gene. NEJM 340: 735-735 [Full Text]  
• Martinelli, I., Taioli, E., Bucciarelli, P., Akhavan, S., Mannucci, P. M. (1999). Interaction Between the G20210A Mutation of the Prothrombin Gene and Oral Contraceptive Use in Deep Vein Thrombosis. Arterioscler. Thromb. Vasc. Bio. 19: 700-703 [Abstract] [Full Text]  
• Kupferminc, M. J., Eldor, A., Steinman, N., Many, A., Bar-Am, A., Jaffa, A., Fait, G., Lessing, J. B. (1999). Increased Frequency of Genetic Thrombophilia in Women with Complications of Pregnancy. NEJM 340: 9-13 [Abstract] [Full Text]  
• Ludemann, P., Nabavi, D. G., Junker, R., Wolff, E., Papke, K., Buchner, H., Assmann, G., Ringelstein, E. B. (1998). Factor V Leiden Mutation Is a Risk Factor for Cerebral Venous Thrombosis : A Case-Control Study of 55 Patients. Stroke 29: 2507-2510 [Abstract] [Full Text]  
• BROWN, M. M, BEVAN, D. (1998). Is inherited thrombophilia a risk factor for arterial stroke?. J. Neurol. Neurosurg. Psychiatry 65: 617-617 [Full Text]  
• Vandenbroucke, J. P (1998). Cerebral sinus thrombosis and oral contraceptives. BMJ 317: 483-484 [Full Text]  
• Bertina, R.M., Rosendaal, F.R. (1998). Venous Thrombosis -- The Interaction of Genes and Environment. NEJM 338: 1839-1841 [Full Text]