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DOI: 10.1055/s-2006-951455
Thromboembolism in Women
Publication History
Publication Date:
06 October 2006 (online)
ABSTRACT
Venous thromboembolism (VTE) occurs in one of every 1000 individuals per year. The incidence is much lower in young persons. In persons younger than age 45, the incidence is one of every 10,000 individuals per year. VTE is a multifactorial disease due to the interaction of various risk factors that can be genetic (e.g., inherited thrombophilia), acquired (e.g., age, neoplastic or autoimmune diseases, antiphospholipid antibodies), or transient (e.g., surgical interventions, fractures, trauma, prolonged immobilization). VTE is found equally in the two sexes. There are other transient risk factors for VTE that are typical for females, and these render women more exposed than men to the risk of the disease during their lifetime. Such risk factors are encountered frequently in a woman's life; they are oral contraceptive (OC) use, hormone replacement therapy, and pregnancy/puerperium. Moreover, various obstetric complications have attributed at least in part to an impaired placental circulation, suggesting a thrombosis theory as their common basis. In this review, the relationship between VTE and risk factors specifically of women is discussed, also in relation to coagulation abnormalities causing inherited thrombophilia.
KEYWORDS
Venous thrombosis - thrombophilia - oral contraceptives - pregnancy - obstetrical complications
REFERENCES
- 1 Martinelli I. Risk factors in venous thromboembolism. Thromb Haemost. 2001; 86 395-403
- 2 WHO Scientific Group on Cardiovascular Disease and Steroid Hormone Contraception . Cardiovascular disease and steroid hormone contraception: Report of a WHO Scientific Group. WHO Technical Report Series. 1998; 877 1-89
- 3 Hannaford P. Health consequences of oral combined oral contraceptives. Br Med Bull. 2000; 56 749-760
- 4 Jordan W M. Pulmonary embolism. Lancet. 1961; 1 1146-1147
- 5 Sartwell P E, Masi A T, Arthes F G, Greene G R, Smith H E. Thromboembolism and oral contraceptives: an epidemiological case control study. Am J Epidemiol. 1969; 90 365-380
- 6 Vessey M P, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease: a further case report. BMJ. 1969; 2 651-657
- 7 Royal College of General Practitioners' Oral Contraception Study . Oral contraceptives, venous thrombosis, and varicose veins. J R Coll Gen Pract. 1978; 28 393-399
- 8 Vessey M, Mant D, Smith A, Yeates D. Oral contraceptives and venous thromboembolism: findings in a large prospective study. BMJ. 1986; 292 526
- 9 Gerstman B B, Piper T M, Tomita D K, Ferguson W J, Stadel B V, Lundin F E. Oral contraceptive estrogen dose and the risk of venous thromboembolic disease. Am J Epidemiol. 1991; 133 32-37
- 10 Bloemenkamp K WM, Rosendaal F R, Helmerhorst F M, Büller H R, Vandenbroucke J P. Enhancement by factor V Leiden mutation of risk of deep vein thrombosis associated with oral contraceptives containing a third generation progestagen. Lancet. 1995; 346 1593-1596
- 11 World Health Organization . Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995; 346 1582-1588
- 12 Jick H, Jick S S, Gurewich V, Myers M W, Vasilakis C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagens components. Lancet. 1995; 346 1589-1593
- 13 Spitzer W O, Lewis M A, Heinemann L A, Thorogood M, MacRae K D. Third generation oral contraceptives and risk of venous thromboembolic disease: an international case-control study. The Transnational Research Group on Oral Contraceptives and the health of Young Women. BMJ. 1996; 312 83-88
- 14 Farmer R DT, Todd J C, Mac Rae K D, Williams T J, Lewis M A. Oral contraception was not associated with venous thromboembolic disease in recent study. BMJ. 1998; 316 1090-1091
- 15 Martinelli I, Taioli E, Bucciarelli P, Akhavan S, Mannucci P M. Interaction between the G20210A mutation of prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol. 1999; 19 700-703
- 16 Bloemenkamp K WM, Rosendaal F R, Büller H R, Helmerhorst F M, Colly I P, Vandenbroucke J P. Risk of venous thrombosis with use of current low-dose oral contraceptives is not explained by diagnostic suspicion and referral bias. Arch Intern Med. 1999; 159 65-70
- 17 Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism. A case-control study. Contraception. 1998; 57 291-301
- 18 Herings R MC, Urquhart J, Leufkens H GM. Venous thromboembolism among new users of different oral contraceptives. Lancet. 1999; 354 127-128
- 19 Lewis M A, Heinemann L A, MacRae K D, Bruppacher R, Spitzer W O. The increased risk of venous thromboembolism and the use of third generation progestagens: role of bias in observational research. The Transnational Research Group on Oral Contraceptives and the health of Young Women. Contraception. 1996; 54 5-13
- 20 Farley T M, Meirik O, Collins J. Cardiovascular disease and combined oral contraceptives: reviewing the evidence and balancing risks. Hum Reprod Update. 1999; 5 721-735
- 21 Vandenbroucke J P, Helmerhorst F M, Bloemenkamp K WM, Rosendaal F R. Third generation oral contraceptive and deep venous thrombosis: from epidemiologic controversy to new insight in coagulation. Am J Obstet Gynecol. 1997; 177 887-891
- 22 Kemmeren J M, Algra A, Grobbee D E. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. BMJ. 2001; 323 131-134
- 23 Vasilakis C, Jick H, Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet. 1999; 354 1610-1611
- 24 Lidegaard Ø, Edström B, Kreiner S. Oral contraceptives and venous thromboembolism: a five-year national case-control study. Contraception. 2002; 65 187-196
- 25 Bloemenkamp K WM, Rosendaal F R, Helmerhorst F, Vandenbroucke J P. Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects. Arch Intern Med. 2000; 160 49-52
- 26 Pabinger I, Schneider B. GTH Study Group . Thrombotic risk of women with hereditary antithrombin III, protein C- and protein S-deficiency taking oral contraceptive medication. Thromb Haemost. 1994; 71 548-552
- 27 Martinelli I. Pros and cons of thrombophilia testing: pros. J Thromb Haemost. 2003; 1 410-411
- 28 Stadel B V. Oral contraceptives and cardiovascular disease. N Engl J Med. 1981; 305 612-618
- 29 Rosendaal F R, van Hylckama-Vlieg A, Tanis B C, Helmerhorst F M. Estrogens, progestogens and thrombosis. J Thromb Haemost. 2003; 1 1371-1380
- 30 Daly E, Vessey M P, Hawkins M M, Carson J L, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet. 1996; 348 977-980
- 31 Jick H, Derby L E, Myers M W, Vasilakis C, Newton K M. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet. 1996; 348 981-983
- 32 Grodstein F, Stampfer M J, Goldhaber S Z et al.. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet. 1996; 348 983-987
- 33 Lowe G DO. Hormone replacement therapy and cardiovascular disease: increased risks of venous thromboembolism and stroke, and no protection from coronary heart disease. J Intern Med. 2004; 256 361-374
- 34 Miller J, Chan B K, Nelson H D. Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the US Preventive Services Task Force. Ann Intern Med. 2002; 136 680-690
- 35 Quinn D A, Thompson B T, Terrin M L et al.. A prospective investigation of pulmonary embolism in women and men. JAMA. 1992; 268 1689-1696
- 36 Herrington D M, Vittinghoff E, Howard R D et al.. Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Arterioscler Thromb Vasc Biol. 2002; 22 1012-1017
- 37 UK Committee on Safety of Medicines and Medicines and Healthcare products Regulatory Agency . HRT: update on the risk of breast cancer and long-term safety. Curr Probl Pharmacovigilance. 2003; 29 1-3
- 38 Burns M M. Emerging concepts in the diagnosis and management of venous thromboembolism during pregnancy. J Thromb Thrombolysis. 2000; 10 59-68
- 39 Hibbard B M, Anderson M M, Drife J O. Report on confidential enquiries into maternal deaths in the United Kingdom 1991-93. London; Her Majesty's Stationery Office 1996
- 40 Greer I A. Thrombosis in pregnancy: maternal and fetal issues. Lancet. 1999; 353 1258-1265
- 41 Royal College of Obstetricians and Gynaecologists. Report of the RCOG Working Party on Prophylaxis against Thromboembolism in Gynaecology and Obstetrics. London; RCOG 1995
- 42 Martinelli I, De Stefano V, Taioli E, Paciaroni K, Rossi E, Mannucci P M. Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium. Thromb Haemost. 2002; 87 791-795
- 43 Macklon N S, Greer I A. Venous thromboembolic disease in obstetrics and gynaecology: the Scottish experience. Scott Med J. 1996; 41 83-86
- 44 Ray J G, Chan W S. Deep vein thrombosis during pregnancy and the puerperium: a metanalysis of the period of risk and the leg of presentation. Obstet Gynecol Surv. 1999; 54 265-271
- 45 Drill V A, Calhoun D W. Oral contraceptives and thromboembolic disease. JAMA. 1968; 206 77-84
- 46 Kierkegaard A. Incidence and diagnosis of deep vein thrombosis associated with pregnancy. Acta Obstet Gynecol Scand. 1983; 62 239-243
- 47 Letzky E, de Swiet M. Thromboembolism in pregnancy and its management. Br J Haematol. 1984; 57 543-552
- 48 Aaro L A, Juergens J L. Thrombophlebitis associated with pregnancy. Am J Obstet Gynecol. 1971; 109 1128-1136
- 49 Lindqvist P, Dahlbäck B, MarŜál K. Thrombotic risk during pregnancy: a population study. Obstet Gynecol. 1999; 94 595-599
- 50 McColl M, Ramsay J E, Tait R C et al.. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost. 1997; 78 1183-1188
- 51 Barbour L A. Current concepts of anticoagulation therapy in pregnancy. Obstet Gynecol Clin North Am. 1997; 24 499-521
- 52 Brill-Edwards P, Ginsberg J S, Gent M et al.. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. N Engl J Med. 2000; 343 1439-1444
- 53 Gerhardt A, Scarf R E, Beckmann M W et al.. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med. 2000; 342 374-380
- 54 Simioni P, Sanson B J, Prandoni P et al.. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost. 1999; 81 198-202
- 55 Grandone E, Margaglione M, Colaizzo D et al.. Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations. Am J Obstet Gynecol. 1998; 179 1324-1328
- 56 Pabinger I, Nemes L, Rintelen C et al.. Pregnancy-associated risk for venous thromboembolism and pregnancy outcome in women homozygous for factor V Leiden. Hematol J. 2000; 1 37-41
- 57 Martinelli I, Legnani C, Bucciarelli P, Grandone E, De Stefano V, Mannucci P M. Risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia. Thromb Haemost. 2001; 86 800-803
- 58 Middeldorp S, Libourel E J, Hamulyák K, van der Meer J, Büller H. The risk of pregnancy-related venous thromboembolism in women who are homozygous for factor V Leiden. Br J Haematol. 2001; 113 553-555
- 59 Friederich P, Sanson B, Simioni P et al.. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Ann Intern Med. 1996; 125 955-960
- 60 Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency. A cooperative, retrospective study. Gesellschaft für Thrombose- und Hämostaseforschung (GTH) Study Group on Natural Inhibitors. Arterioscler Thromb Vasc Biol. 1996; 16 742-748
- 61 Hough R, Makris M, Preston F. Pregnancy in women with thrombophilia: incidence of thrombosis and pregnancy outcome. Br J Haematol. 1996; 93(suppl 2) 136
- 62 Stirrat G M. Recurrent miscarriage. I. Definition and epidemiology. Lancet. 1990; 336 673-675
- 63 Lindqvist P G, Merlo J. Low molecular weight heparin for repeated pregnancy loss: is it based on solid evidence?. J Thromb Haemost. 2005; 3 221-223
- 64 Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005; 365 785-799
- 65 Göpel W, Kim D, Gortner L. Prothrombotic mutations as a risk factor for preterm birth. Lancet. 1999; 353 1411-1412
- 66 Grandone E, Margaglione M, Colaizzo D et al.. Prothrombotic genetic risk factors and the occurrence of gestational hypertension with and without proteinuria. Thromb Haemost. 1999; 81 349-352
- 67 Facchinetti F, Marozio L, Grandone E, Pizzi C, Volpe A, Benedetto C. Thrombophilic mutations are a main risk factor for placental abruption. Haematologica. 2003; 88 785-788
- 68 Regan L, Rai R. Thrombophilia and pregnancy loss. J Reprod Immunol. 2002; 55 163-180
- 69 Vossen C, Preston F E, Conard J et al.. Hereditary thrombophilia and fetal loss: a prospective follow-up study. J Thromb Haemost. 2004; 2 592-596
Ida MartinelliM.D. Ph.D.
A. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital Policlinico
Via Pace, 9, 20122 Milan, Italy
Email: martin@policlinico.mi.it