Association of Elevated Soluble P-Selectin Levels and Fetal Loss in Women with a History of Venous Thromboembolism.

Pregnancy is a hypercoagulable state with an increased risk of venous thromboembolism (VTE). Furthermore, accumulating evidence support the hypothesis that pregnancy complications such as fetal loss are associated with both inherited and acquired thrombophilic defects which may predispose to thrombosis of the placental vasculature and lead to subsequent fetal loss. In recent studies the cell adhesion molecule P-selectin has been identified to be a strong risk factor for VTE. Interestingly, soluble P-selectin (sP-selectin) plasma levels were previously reported to increase during pregnancy. Whether P-selectin is also associated with fetal loss in women with a history of venous thromboembolism, is not known yet. Therefore, the aim of our present study was to investigate the significance of elevated sP-selectin levels for fetal loss (e.g. miscarriage or stillbirth) in women with a history of VTE. We retrospectively evaluated data on pregnancy-associated complications in 304 women (mean age [+/-SD]: 45.6 [+/-11.5] yrs) with a history of VTE. sP-selectin plasma levels were measured using a sensitive ELISA (sP-selectin Immunoassay, R&D Systems®, Minneapolis, MN, USA). At the time of measurement of sP-selectin none of the women was pregnant and did not have an acute event of VTE. The mean age (±SD) of patients at the time of the VTE event was 31.3 (+/- 8.4) yrs. The prevalence of miscarriage (defined as intrauterine fetal death before the 24^th week of gestation or when fetus weighed <500 g) in our study population was 21.8% and the prevalence of stillbirth (defined as intrauterine fetal death at or after the 24^th week of gestation) was 4.3%. Median (interquartile range [IQR]) sP-selectin level of the total study population was 38.0 [21.7-44.4] ng/mL. The cut-off point for elevated sP-selectin was set at 44.4 ng/mL, which represents the 75^th percentile of sP-selectin levels of the study population. The prevalence of stillbirth was significantly higher in subjects with elevated sP-selectin levels compared to those with lower levels (10.5% vs. 2.6%, p=0.008), whereas no statistically significant difference in prevalence of miscarriage was observed between women with and without elevated sP-selectin (17.1% vs. 22.9%, p=0.303). The odds ratio [95% CI] of elevated sP-selectin for stillbirth was 4.2 [1.5-12.7] and for miscarriage 0.7 [0.4-1.3]. In summary, elevated sP-selectin plasma levels were associated with a 4-fold risk for stillbirth in women with a history of VTE. Our data support a possible role of P-selectin in the aetiology of late pregnancy complications.