Sex and gender issues and venous thromboembolism

At least 250,000 episodes of VTE leading to hospitalization or death are estimated to occur in the United States each year. A number of clinical and demographic risk factors for VTE are recognized,with the latter including both age and race. Overall,the incidence of VTE does not appear to vary significantly by sex, as evidenced by a lack of consistency in the magnitude and even direction of effect of sex in a variety of epidemiologic studies of varying design. Several studies have shown a higher incidence among women than men during childbearing age. The issue of a gender effect on the natural history of VTE has not been well studied. The main influence of gender on VTE is the relationship between female gender and several well-recognized clinical risk factors for VTE:oral contraceptive use, hormone replacement therapy, estrogen receptor modulator therapy, and pregnancy. Hormonal therapies are associated with a twofold to threefold increase in VTE incidence. Risk is higher with some formulations than others, during initial use, and among women who are obese, smoke, or have one of several forms of heritable thrombophilia. The pregnant state is associated with a threefold to fivefold increase in VTE risk, and thromboembolism is a major cause of peripartum death. Heritable thrombophilias are also important co-determinants of VTE risk in pregnancy. The mechanisms through which pregnancy and hormonal therapies increase VTE risk have not been definitively established, but hormonal effects on levels of coagulation and anticoagulation factors likely play a role. Venous compression and venous injury also contribute to increased risk during pregnancy and the puerperium. Approaches to diagnosis of VTE in the pregnant woman are largely the same as in the nonpregnant patient, but special treatment considerations do apply. Warfarin is embryopathic, particularly between the 6th and 12th weeks of pregnancy, and should be avoided in favor or heparin or low-molecular weight heparin when treatment of the pregnant woman is necessary. Guidelines have been published to assist the clinician in decision making about prophylaxis of pregnant women at increased risk or pregnancy-related or post-partum VTE.