Table 10.5 Oral Contraceptive Estrogen Dose and Risk for Deep Vein Thrombosis aBaseline risk used to calculate risk for higher doses. From Gerstman BB, Piper JM, Tomita DK, et al. Oral contraceptive dose and the risk of deep venous thrombosis. Am J Epidemiol 1991;133:32–37, with permission.
Table 10.6 Crude Incidence Rates and Adjusted Rate Ratios of Venous Thrombosis in Women Using Different Types of Hormonal Contraception
OC, oral contraceptive; IUD, intrauterine device. aAdjusted for current use of oral contraceptives, calendar year, and educational level. bAdjusted for age, calendar year, and educational level. From Lidegaard O, Lokkegaard E, Svendsen AL, et al. Hormonal contraception and risk of venous thromboembolism: national follow up study. BMJ 2009;339:b2890 [Table I on page 3], with permission.
Caucasian population. It codes for a one amino acid mutation in the factor V protein, inhibiting cleavage of the protein by activated protein C, which is an essential step in maintaining the balance between coagulation and fibrinolysis (109,132). Risk for a first thromboembolic episode among women using OCs was 2.2 per 10,000 woman-years for women without the factor V mutation and 27.7 per 10,000 woman-years for women with the mutation (133). Cigarette smoking did not affect this risk. There are pronounced ethnic differences in the presence of this mutation. The Leiden allele is found in 3% to 5% of whites but is rare in Africans, Asians, Amerindians, Eskimos, and Polynesians (134). A similar mutation is found in the prothrombin gene at position 20210 and is described as prothrombin G20210A. This mutation occurs in 3% of the European population and is strongly associated with venous thrombosis in women taking OCs (135). Many more genetic conditions predisposing to thrombosis were described. Pregnancy is an even greater challenge for women with inherited defects of anticoagulation (136). A woman who sustains a venous event while using OCs should be evaluated thoroughly after she has recovered. Assessment should include at minimum the measurement of antithrombin III, protein C, and protein S levels, resistance to activated protein C, serum homocysteine, factor V Leiden mutation, the prothrombin G20210A mutation and testing for antiphospholipid syndrome. It should not be assumed that hormonal contraception was the unique cause of the thrombotic episode.
Routine screening for all women before prescribing hormonal contraception is not justified because effective contraception would be denied to 5% of Caucasian women, and only a small number of fatal pulmonary emboli would be prevented (137,138). Screening women with a personal or family history of deep vein thrombosis before starting estrogen-containing hormonal contraception or pregnancy is strongly recommended. Women already diagnosed as having factor V Leiden should not receive estrogen-containing contraceptives, i.e., the pill, patch or ring.