Heath Management Center, Second Xiangya Hospital, Central South University, Changsha 410011.
Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha 410011.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Apr 28;47(4):469-478. doi: 10.11817/j.issn.1672-7347.2022.210536.
There is a high coagulation state in pregnant women, which is prone to coagulation and fibrinolysis system dysfunction. This study aims to explore the latest coagulation markers-thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator/plasminogen activator inhibitor compound (tPAI-C) in different stages of pregnancy, establish reference intervals (RIs) for healthy pregnant women of Chinese population, and to provide an effective and reliable reference for clinicians.
A total of 492 healthy pregnant women, who underwent pregnancy examination and delivery in the Department of Obstetrics, Second Xiangya Hospital of Central South University from October 2019 to October 2020, were enrolled for this study. They were assigned into the first trimester group, the second trimester group, the third trimester group, and the puerperium group according to the pregnancy period, and 123 healthy non-pregnant women were selected as the controls. Plasma levels of TM, TAT, PIC and tPAI-C were analyzed by automatic chemiluminescence immunoassay analyzer. The RIs for TM, TAT, PIC, and tPAI-C were defined using non-parametric 95% intervals, determined following Clinical and Laboratory Standards Institute Document C28-A3c (CLSI C28-A3c), and Formulation of Reference Intervals for the Clinical Laboratory Test Items (WS/T402-2012).
TM and TAT levels increased gradually in the first, second, and third trimester women and decreased in the puerperium women (<0.05 or <0.01). PIC level of healthy non-pregnant women was lower than that of pregnant women (<0.05 or <0.01), but PIC level of pregnant and puerperium women did not differ significantly (>0.05). tPAI-C level in healthy non-pregnant women was lower than that of pregnant women (<0.05 or <0.01), and tPAI-C level was significantly decreases in the puerperium women (<0.01). The RIs for TM were as follows: Healthy non-pregnant women at 3.20-4.60 TU/mL, the first and second trimester at 3.12-7.90 TU/mL, the third trimester at 3.42-8.29 TU/mL, puerperium at 2.70-6.40 TU/mL. The RIs for TAT were as follows: Healthy non-pregnant women at 0.50-1.64 ng/mL, the first and second trimester at 0.52-6.91 ng/mL, the third trimester at 0.96-12.92 ng/mL, puerperium at 0.82-3.75 ng/mL. The RIs for PIC were as follows: Healthy non-pregnant women at 0.160-0.519 ng/mL, pregnant women at 0.162-0.770 μg/mL. The RIs for tPAI-C were as follows: Healthy non-pregnant women at 1.90-4.80 ng/mL, the first and second trimester at 2.03-9.33 ng/mL, the third trimester at 2.80-14.20 ng/mL, puerperium at 1.10-8.40 ng/mL.
The levels of 4 new coagulation markers TM, TAT, PIC, and tPAI-C in pregnant women are increased significantly during pregnancy and gradually return to normal after delivery. The RIs for TM, TAT, PIC, and tPAI-C in pregnant women by trimester are established according to CLSI C28-A3c, thus providing a clinical reference for clinician in judgement of thrombotic risk.
孕妇存在高凝状态，易发生凝血及纤溶系统功能障碍。本研究旨在探讨新型凝血标志物血栓调节蛋白（TM）、凝血酶-抗凝血酶复合物（TAT）、纤溶酶-α2 纤溶酶抑制物复合物（PIC）和组织型纤溶酶原激活物/纤溶酶原激活物抑制物复合物（tPAI-C）在不同孕期的变化，建立中国人群健康孕妇的参考区间（RI），为临床医生提供有效可靠的参考。
选取 2019 年 10 月至 2020 年 10 月在中南大学湘雅二医院妇产科进行妊娠检查和分娩的 492 例健康孕妇，根据妊娠周期分为早孕期组、中孕期组、晚孕期组和产褥期组，另选取 123 例健康未孕女性作为对照组。采用全自动化学发光免疫分析仪分析 TM、TAT、PIC 和 tPAI-C 水平。采用非参数 95%区间法（CLSI C28-A3c）和《临床实验室检验项目参考区间的制定》（WS/T402-2012）定义 TM、TAT、PIC 和 tPAI-C 的 RI。
TM 和 TAT 水平在早、中、晚孕期逐渐升高，产褥期降低（<0.05 或 <0.01）。健康未孕女性的 PIC 水平低于孕妇（<0.05 或 <0.01），但孕妇和产褥期女性的 PIC 水平无显著差异（>0.05）。健康未孕女性的 tPAI-C 水平低于孕妇（<0.05 或 <0.01），产褥期女性的 tPAI-C 水平显著降低（<0.01）。TM 的 RI 如下：健康未孕女性为 3.20-4.60 TU/mL，早孕期和中孕期为 3.12-7.90 TU/mL，晚孕期为 3.42-8.29 TU/mL，产褥期为 2.70-6.40 TU/mL。TAT 的 RI 如下：健康未孕女性为 0.50-1.64 ng/mL，早孕期和中孕期为 0.52-6.91 ng/mL，晚孕期为 0.96-12.92 ng/mL，产褥期为 0.82-3.75 ng/mL。PIC 的 RI 如下：健康未孕女性为 0.160-0.519 ng/mL，孕妇为 0.162-0.770 μg/mL。tPAI-C 的 RI 如下：健康未孕女性为 1.90-4.80 ng/mL，早孕期和中孕期为 2.03-9.33 ng/mL，晚孕期为 2.80-14.20 ng/mL，产褥期为 1.10-8.40 ng/mL。
孕妇在妊娠期间 4 种新型凝血标志物 TM、TAT、PIC 和 tPAI-C 的水平显著升高，分娩后逐渐恢复正常。本研究根据 CLSI C28-A3c 建立了孕妇各孕期 TM、TAT、PIC 和 tPAI-C 的 RI，为临床医生判断血栓风险提供了参考。
