Wallaschofski H, Donné M, Eigenthaler M, Hentschel B, Faber R, Stepan H, Koksch M, Lohmann T
Department of Internal Medicine III, University of Leipzig, Germany.
J Clin Endocrinol Metab. 2001 Dec;86(12):5912-9. doi: 10.1210/jcem.86.12.8085.
Pregnancy (including puerperium) is a period of hypercoagulability and seems to be an independent major risk factor for venous thromboembolism (VTE). However, the basis of the increased risk of VTE in pregnancy and around delivery is unknown. We hypothesized that changes in PRL, which is a prominently increased hormone during pregnancy and lactation, might be involved in the activation of platelets. To investigate platelet functional abnormalities in pregnancy, we assessed the ADP-stimulated and nonstimulated P-selectin expression of platelets in 42 consecutive pregnant women, 22 normo- and hyperprolactinemic patients with pituitary tumors, and controls. In addition, the aggregation of platelets by human PRL in vitro was studied. We found a significant correlation between PRL values and ADP stimulation of platelets in pregnant women (r = 0.56; P < 0.0001) and patients with pituitary tumors (r = 0.57; P = 0.006). Hyperprolactinemic pregnant women or hyperprolactinemic patients with pituitary tumors revealed significantly higher ADP stimulation of platelets (P < 0.0001) than healthy controls or normoprolactinemic patients with pituitary tumors. These results were reconciled by increased in vitro stimulation and aggregation of platelets using human PRL. Our novel findings demonstrate that hyperprolactinemia causes increased platelet aggregation via ADP stimulation both in vitro and in vivo. Moreover, our data indicate that PRL may be a physiological cofactor of the delicate coagulation balance during pregnancy and puerperium that might explain the increased risk of VTE in pregnant women around delivery. Further studies of the interaction between PRL and platelets will clarify the clinical relevance of hyperprolactinemia as a potential risk factor for VTE.
妊娠(包括产褥期)是一个血液高凝期,似乎是静脉血栓栓塞症(VTE)的一个独立主要危险因素。然而,妊娠期间及分娩前后VTE风险增加的原因尚不清楚。我们推测,催乳素(PRL)在妊娠和哺乳期显著升高,其变化可能与血小板激活有关。为研究妊娠期间血小板功能异常,我们评估了42例连续妊娠妇女、22例垂体瘤导致的正常催乳素血症和高催乳素血症患者以及对照组中血小板经二磷酸腺苷(ADP)刺激和未刺激时P选择素的表达。此外,还研究了人PRL在体外对血小板的聚集作用。我们发现,妊娠妇女(r = 0.56;P < 0.0001)和垂体瘤患者(r = 0.57;P = 0.006)的PRL值与血小板ADP刺激之间存在显著相关性。高催乳素血症的妊娠妇女或垂体瘤导致的高催乳素血症患者的血小板ADP刺激显著高于健康对照组或垂体瘤导致的正常催乳素血症患者(P < 0.0001)。使用人PRL进行体外刺激和血小板聚集增加证实了这些结果。我们的新发现表明,高催乳素血症在体外和体内均可通过ADP刺激导致血小板聚集增加。此外,我们的数据表明,PRL可能是妊娠和产褥期精细凝血平衡的生理辅助因子,这可能解释了分娩前后孕妇VTE风险增加的原因。对PRL与血小板相互作用的进一步研究将阐明高催乳素血症作为VTE潜在危险因素的临床相关性。