A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families

Abstract

Why men appear to have an increased risk of recurrent venous thrombosis compared with women is unknown. In a cohort study of families with thrombophilia, lifetime risk of recurrent venous thrombosis was assessed in men and women (n ‫؍‬ 816). Adjusted relative risk of recurrence was 1.6 (95% CI, 1.3-2.0) in men compared with women. Women were younger at time of their first event (mean, 34 years vs 44 years; P < .001) and at time of recurrence (40 years vs 48 years, P < .001). After excluding provoked first and recurrent venous thrombosis, adjusted relative risk was 1.2 (95% CI, 0.8-1.7), although mean age at recurrence was comparable in men and women (50 years vs 49 years, P ‫؍‬ .595). In women with a hormonal first event, median interval between first event and recurrence was 10.4 years versus 2.7 years in men (P < .001). This difference was not observed when only unprovoked events were considered (P ‫؍‬ .938). The difference in lifetime risk of recurrent venous thrombosis between men and women in thrombophilic families can be explained by a younger age of women at time of first venous thrombosis due to hormonal risk factors, and a longer interval between a provoked first episode of venous thrombosis and recurrence in women. (Blood.

Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study

“…41,42 Neither sex nor idiopathic VTE were independent predictors of 180-day VTE recurrence. Sex was not an independent predictor of recurrence in our previous study, 17 a finding that was recently confirmed, 43 and idiopathic VTE was not a predictor of recurrence during initial anticoagulation therapy in previous studies. 42,44 The number of major bleeding events (n ϭ 12) was too few for meaningful multivariable analysis.…”

Sex Difference in Risk of Second but Not of First Venous Thrombosis

“…[10][11][12][13][14] Studies have shown that men have a 2-fold higher risk of recurrent venous thrombosis than women. [10][11][12][13][14] It was hypothesized that this could be explained by a reduction in exposure to reproductive risk factors in women [10][11][12][13]15 because women who experience a first venous thrombosis are encouraged to discontinue the use of hormonal preparations or to use thromboprophylaxis in future pregnancies. [21][22][23] However, population-based studies that compared men with women who had a first venous thrombosis that was not related to reproductive risk factors still showed a 2-fold higher risk of recurrence in men.…”

“…12,15 Because there is no such male-specific transient risk factor, [1][2][3][4][5][6][7] we hypothesized that female exposure to reproductive risk factors masks an intrinsically higher risk of venous thrombosis in men because the incidence of first venous thrombosis is still similar in men and women. We therefore set out to formally assess the risk of first venous thrombosis in men compared with women with and without reproductive risk factors.…”

Epidemiology of recurrent venous thrombosis

“…It could be explained by an imbalance of environmental risk factors for venous thrombosis in men compared to women, for example, due to hormonal risk factors to which only women are exposed. As oral contraceptives are discouraged after first venous thrombosis and thromboprophylaxis is often recommended in women during pregnancy or puerperium after a first event (22,23), women may have a lower thrombosis potential level for recurrence than men in whom environmental risk factors are less often associated with risk for a first venous thrombosis (24). Some studies indeed suggested that the lower risk of recurrent venous thrombosis in women could be explained by a reduced rate of recurrence after venous thrombosis associated with oral contraceptive use or pregnancy (24-26).…”