Toth Bettina, Nieuwland Rienk, Kern Meike, Rogenhofer Nina, Berkmans René, Rank Andreas, Lohse Peter, Friese Klaus, Thaler Christian J
Department of Obstetrics and Gynecology-Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Am J Reprod Immunol. 2008 Feb;59(2):159-66. doi: 10.1111/j.1600-0897.2007.00550.x.
Placental fibrin deposits in patients wih recurrent spontaneous abortion (RSA) indicate an exaggerated haemostatic response. This 'hypercoagulability' may involve pro-coagulant factors such as circulating microparticles (MPs). We investigated the relationship between circulating pro-coagulant MPs and systemic coagulation in RSA patients.
Platelet- and endothelial cell-derived microparticles (PMPs, EMPs) were evaluated by flow cytometry in RSA patients (n = 51) and compared to controls (n = 24) using annexin V (total numbers of MP), and antibodies against CD61, CD63 and CD62P (PMP), as well as CD144 and CD62E (EMP). Prothrombin fragment 1 + 2 (F(1+2)) and thrombin generation were determined to assess the pro-coagulant potential of MP.
Numbers of annexin V-binding MP were nearly similar in RSA patients and controls. However, a subgroup of ten RSA patients (10/51; 20%) presented with MP concentrations >10,000 x 10(6)/L, compared to only one women out of the control group (1/24; 4%; P = 0.038). Neither PMP and EMP nor F(1+2) and thrombin generation differed significantly within the study population.
The present study shows that circulating MPs are not directly associated with the extent of systemic coagulation activation in RSA patients. We hypothesize that increased numbers of circulating MPs either are only indirectly associated with coagulation during pregnancy of RSA patients, or affect abortion via mechanisms independently from hypercoagulation.
复发性自然流产(RSA)患者胎盘纤维蛋白沉积表明止血反应过度。这种“高凝状态”可能涉及促凝血因子,如循环微粒(MPs)。我们研究了RSA患者循环促凝血MPs与全身凝血之间的关系。
通过流式细胞术评估RSA患者(n = 51)血小板和内皮细胞衍生的微粒(PMPs、EMPs),并使用膜联蛋白V(MP总数)以及抗CD61、CD63和CD62P(PMP)抗体,以及抗CD144和CD62E(EMP)抗体与对照组(n = 24)进行比较。测定凝血酶原片段1 + 2(F(1+2))和凝血酶生成以评估MP的促凝血潜力。
RSA患者和对照组中膜联蛋白V结合MP的数量几乎相似。然而,有10名RSA患者(10/51;20%)的MP浓度>10,000×10(6)/L,而对照组中只有1名女性(1/24;4%;P = 0.038)。在研究人群中,PMP和EMP以及F(1+2)和凝血酶生成均无显著差异。
本研究表明,RSA患者循环MPs与全身凝血激活程度无直接关联。我们推测,RSA患者孕期循环MPs数量增加要么仅与凝血间接相关,要么通过独立于高凝状态的机制影响流产。