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 342:374-380 February 10, 2000 Number 6 Next

	Full Text PDF Editorial by Greer, I. A. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Venous thromboembolism is a leading cause of morbidity and mortality during pregnancy and the puerperium. However, the role of mutations in the prothrombin and factor V genes and other thrombophilic abnormalities as risk factors for thromboembolism in women during pregnancy and the puerperium is not known.

Methods In a study of 119 women with a history of venous thromboembolism during pregnancy and the puerperium and 233 age-matched normal women, we measured the activity of antithrombin, protein C, protein S, and lupus anticoagulant. We also performed genetic analyses to detect the G1691A mutation in the factor V gene (factor V Leiden), the G20210A mutation in the prothrombin gene, and the C677T mutation in the methylenetetrahydrofolate reductase gene. Blood samples were obtained at least three months post partum or after the cessation of lactation.

Results Among the women with a history of venous thromboembolism, the prevalence of factor V Leiden was 43.7 percent, as compared with 7.7 percent among the normal women (relative risk of venous thromboembolism, 9.3; 95 percent confidence interval, 5.1 to 16.9); that of the G20210A prothrombin-gene mutation, 16.9 percent as compared with 1.3 percent (relative risk, 15.2; 95 percent confidence interval, 4.2 to 52.6); and that of both factor V Leiden and the G20210A prothrombin-gene mutation, 9.3 percent as compared with 0 (estimated odds ratio, 107). Assuming an overall risk of 1 in 1500 pregnancies, the risk of thrombosis among carriers of factor V Leiden was 0.2 percent, among carriers of the G20210A prothrombin-gene mutation, 0.5 percent, and among carriers of both defects, 4.6 percent, as calculated in a multivariate analysis.

Conclusions The G20210A prothrombin-gene mutation and factor V Leiden individually are associated with an increased risk of venous thromboembolism during pregnancy and the puerperium, and the risk among women with both mutations is disproportionately higher than that among women with only one mutation.

Source Information

From the Departments of Hemostasis and Transfusion Medicine (A.G., R.E.S., R.B.Z.), Obstetrics and Gynecology (M.W.B., S.S., H.G.B.), and Vascular Surgery and Kidney Transplantation (M.P., W.S.), Heinrich Heine University Medical Center, Düsseldorf, Germany.

Address reprint requests to Dr. Zotz at the Institut für Haemostaseologie und Transfusionsmedizin, Heinrich Heine Universität, Moorenstr. 5, D-40225 Düsseldorf, Germany, or at zotz{at}med.uni-duesseldorf.de.

Full Text of this Article

Related Letters:

Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium
Moll S., Escobar M., Zotz R. B., Gerhardt A., Scharf R. E.
Extract | Full Text  
N Engl J Med 2000; 342:1996-1997, Jun 29, 2000. Correspondence

This article has been cited by other articles:

• James, A. H. (2009). Venous Thromboembolism in Pregnancy. Arterioscler. Thromb. Vasc. Bio. 29: 326-331 [Abstract] [Full Text]  
• GIBSON, P. S., POWRIE, R. (2009). Anticoagulants and pregnancy: When are they safe?. Cleveland Clinic Journal of Medicine 76: 113-127 [Abstract] [Full Text]  
• Zee, R. Y.L., Glynn, R. J., Cheng, S., Steiner, L., Rose, L., Ridker, P. M (2009). An Evaluation of Candidate Genes of Inflammation and Thrombosis in Relation to the Risk of Venous Thromboembolism: The Women's Genome Health Study. Circ Cardiovasc Genet 2: 57-62 [Abstract] [Full Text]  
• Bates, S. M., Greer, I. A., Pabinger, I., Sofaer, S., Hirsh, J. (2008). Venous Thromboembolism, Thrombophilia, Antithrombotic Therapy, and Pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 844S-886S [Abstract] [Full Text]  
• Dolek, B., Eraslan, S., Eroglu, S., Kesim, B. E., Ulutin, T., Yalciner, A., Laleli, Y. R., Gozukirmizi, N. (2007). Molecular Analysis of Factor V Leiden, Factor V Hong Kong, Factor II G20210A, Methylenetetrahydrofolate Reductase C677T, and A1298C Mutations Related to Turkish Thrombosis Patients. CLIN APPL THROMB HEMOST 13: 435-438 [Abstract]  
• Quiroga, T., Goycoolea, M., Panes, O., Aranda, E., Martinez, C., Belmont, S., Munoz, B., Zuniga, P., Pereira, J., Mezzano, D. (2007). High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls. haematol 92: 357-365 [Abstract] [Full Text]  
• Bates, S. M. (2007). Management of Pregnant Women with Thrombophilia or a History of Venous Thromboembolism. ASH Education Book 2007: 143-150 [Abstract] [Full Text]  
• Merriman, L, Greaves, M (2006). Testing for thrombophilia: an evidence-based approach. Postgrad. Med. J. 82: 699-704 [Abstract] [Full Text]  
• 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]  
• Bates, S. M., Greer, I. A., Hirsh, J., Ginsberg, J. S. (2004). Use of Antithrombotic Agents During Pregnancy: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 627S-644S [Abstract] [Full Text]  
• Langan, R. C. (2004). Factor V Leiden Mutation and Pregnancy. J Am Board Fam Med 17: 306-308 [Full Text]  
• Donahue, B. S. (2004). Factor V Leiden and Perioperative Risk. Anesth. Analg. 98: 1623-1634 [Abstract] [Full Text]  
• Brenner, B. (2004). Clinical management of thrombophilia-related placental vascular complications. Blood 103: 4003-4009 [Abstract] [Full Text]  
• Hao, K., Wang, X., Niu, T., Xu, X., Li, A., Chang, W., Wang, L., Li, G., Laird, N., Xu, X. (2004). A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods. Hum Mol Genet 13: 683-691 [Abstract] [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]  
• 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]  
• Westrich, G. H., Weksler, B. B., Glueck, C. J., Blumenthal, B. F., Salvati, E. A. (2002). Correlation of Thrombophilia and Hypofibrinolysis with Pulmonary Embolism Following Total Hip Arthroplasty: An Analysis of Genetic Factors. JBJS 84: 2161-2167 [Abstract] [Full Text]  
• Dalen, J. E. (2002). Pulmonary Embolism: What Have We Learned Since Virchow?: Natural History, Pathophysiology, and Diagnosis. Chest 122: 1440-1456 [Full Text]  
• Bloomenthal, D., von Dadelszen, P., Liston, R., Magee, L., Tsang, P. (2002). The effect of factor V Leiden carriage on maternal and fetal health. CMAJ 167: 48-54 [Abstract] [Full Text]  
• Simioni, P., Tormene, D., Prandoni, P., Zerbinati, P., Gavasso, S., Cefalo, P., Girolami, A. (2002). Incidence of venous thromboembolism in asymptomatic family members who are carriers of factor V Leiden: a prospective cohort study. Blood 99: 1938-1942 [Abstract] [Full Text]  
• Arkel, Y. S., Ku, D.-H. W. (2001). State-of-the-Art Review: Thrombophilia and Pregnancy: Review of the Literature and Some Original Data. CLIN APPL THROMB HEMOST 7: 259-268 [Abstract]  
• Bauer, K. A. (2001). The Thrombophilias: Well-Defined Risk Factors with Uncertain Therapeutic Implications. ANN INTERN MED 135: 367-373 [Abstract] [Full Text]  
• Botto, L. D., Khoury, M. J. (2001). Commentary: Facing the Challenge of Gene-Environment Interaction: The Two-by-Four Table and Beyond. Am J Epidemiol 153: 1016-1020 [Abstract] [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]  
• Ginsberg, J. S., Greer, I., Hirsh, J. (2001). Use of Antithrombotic Agents During Pregnancy. Chest 119: 122S-131S [Full Text]  
• Cui, J., Eitzman, D. T., Westrick, R. J., Christie, P. D., Xu, Z. J., Yang, A. Y., Purkayastha, A. A., Yang, T. L., Metz, A. L., Gallagher, K. P., Tyson, J. A., Rosenberg, R. D., Ginsburg, D. (2000). Spontaneous thrombosis in mice carrying the factor V Leiden mutation. Blood 96: 4222-4226 [Abstract] [Full Text]  
• Moll, S., Escobar, M., Zotz, R. B., Gerhardt, A., Scharf, R. E. (2000). Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium. NEJM 342: 1996-1997 [Full Text]  
• (2000). Venous Thromboembolism During Pregnancy. Journal Watch Dermatology 2000: 13-13 [Full Text]  
• (2000). Familial Conditions That Increase Risk for Thrombosis During Pregnancy. JWatch Women's Health 2000: 5-5 [Full Text]  
• (2000). Venous Thromboembolism During Pregnancy. JWatch General 2000: 3-3 [Full Text]  
• Greer, I. A. (2000). The Challenge of Thrombophilia in Maternal-Fetal Medicine. NEJM 342: 424-425 [Full Text]