Romagnuolo Ilaria, Attanasio Monica, Cozzolino Mauro, Paladino Enrichetta, Castaman Giancarlo, Coccia Maria E, Fatini Cinzia
Department of Experimental and Clinical Medicine, University of Florence.
Coagulative and Hemorrhagic Diseases Center, Oncology Department, AOU-Careggi.
Blood Coagul Fibrinolysis. 2018 Mar;29(2):160-166. doi: 10.1097/MBC.0000000000000675.
: An adequate hemostatic balance is mandatory to get successful pregnancy. Obstetric complications, such as recurrent pregnancy loss (RPL), might be due to an impairment of placental perfusion possibly related to an underlying prothrombotic status. In this study, we used the global coagulation assay, calibrated automated thrombography and traditional coagulation assay to search for a possible underlying hypercoagulable status in women with history of RPL compared with uneventful pregnancy women. Thrombin generation, Fibrinogen, factor VIII (FVIII), Plasminogen Activator Inhibitor-1 (PAI-1) and von Willebrand factor levels were analyzed in 92 not pregnant unexplained RPL and 64 uneventful pregnancy women. In RPL women, significantly higher fibrinogen, FVIII and PAI-1 levels, and thrombin generation with respect to those observed in uneventful pregnancy women were found. By dividing the study population into quartiles of endogenous thrombin potential (ETP), a lower percentage of RPL women than uneventful pregnancy women in the second quartile was observed, whereas a higher percentage of RPL in comparison with uneventful pregnancy women in the third and fourth quartile was found (P = 0.009). Accordingly, the cut-off ETP of 1222.1 nmol/l was chosen; ETP above cut-off concentration was associated with more than two-fold increased risk of RPL (P = 0.008), also after adjustment for traditional risk factors (P = 0.009). We provided evidence of an underlying alteration of vascular network related to increased coagulation components, and fibrinolysis inhibitor levels in healthy women with history RPL; therefore, calibrated automated thrombography global assay and testing for FVIII and PAI-1 would be advisable in clinical practice to evaluate the hypercoagulable status in RPL women planning future pregnancy.
获得成功妊娠必须有适当的止血平衡。产科并发症，如复发性流产（RPL），可能是由于胎盘灌注受损，这可能与潜在的血栓前状态有关。在本研究中，我们使用全球凝血测定、校准自动血栓形成测定和传统凝血测定，以寻找有RPL病史的女性与正常妊娠女性相比可能存在的潜在高凝状态。分析了92例不明原因未孕RPL女性和64例正常妊娠女性的凝血酶生成、纤维蛋白原、因子VIII（FVIII）、纤溶酶原激活物抑制剂-1（PAI-1）和血管性血友病因子水平。在RPL女性中，发现纤维蛋白原、FVIII和PAI-1水平以及凝血酶生成明显高于正常妊娠女性。通过将研究人群分为内源性凝血酶潜力（ETP）四分位数，观察到第二四分位数中RPL女性的比例低于正常妊娠女性，而在第三和第四四分位数中，RPL女性的比例高于正常妊娠女性（P = 0.009）。因此，选择1222.1 nmol/l的ETP临界值；ETP高于临界浓度与RPL风险增加两倍以上相关（P = 0.008），在调整传统风险因素后也是如此（P = 0.009）。我们提供了证据，表明有RPL病史的健康女性存在与凝血成分增加和纤溶抑制水平相关的血管网络潜在改变；因此，在临床实践中，建议使用校准自动血栓形成全球测定以及检测FVIII和PAI-1，以评估计划未来妊娠的RPL女性的高凝状态。
