Gender-specific and menstrual cycle dependent differences in circulating microparticles

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Abstract
In comparison to age-matched men, young women are at increased risk to suffer from venous thromboembolism (VTE). Some risk factors of inherited and acquired thrombophilia are known, but approximately 30% of the overall risk remains unexplained. Recently, a role for microparticles (MP) in coagulation has been suggested. We investigated, if gender- and menstrual cycle-specific differences in circulating MP exist. Platelet- and endothelial cell-derived microparticles (PMP, EMP) and subpopulations thereof were evaluated flow-cytometrically in healthy women (n = 27) in different phases of their menstrual cycles (follicular phase: n = 14, luteal phase: n = 13) and in healthy men (n = 18). Additionally, D-dimer levels were determined. Compared to men, women had elevated numbers of annexin V-binding MP (p = 0.007), PMP (CD61; p = 0.013), P-selectin-exposing PMP (p = 0.002) and E-selectin-exposing EMP (p = 0.009). During the luteal phase, women had strongly elevated concentrations of MP, PMP, P-selectin- and CD63-exposing PMP as well as E-selectin-exposing EMP (p = 0.001, p < 0.001, p = 0.004, p = 0.003, and p < 0.001, respectively), and the ratio of P-selectin-exposing PMP/platelet increased more than three-fold as compared to men (p = 0.01). When different phases of the menstrual cycle were analysed, MP (annexin V; p = 0.025), PMP (CD61: p < 0.001; CD63: p = 0.015) and E-Selectin-positive EMP (p = 0.006) were all increased in the luteal phase. Although D-dimer concentrations in women were increased compared to men (p = 0 = 0.006), no menstrual cycle-specific differences were observed. In summary, circulating MP and subpopulations thereof are increased in women when compared to men, and this increase seems to be modulated by the menstrual cycle. Therefore, circulating MP may be an additional risk factor contributing to the hitherto unexplained procoagulatory state of young women.

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