Dong Feng, Lv Zhongxing, Di Ping
Department of Clinical Laboratory, Beijing Jishuitan Hospital, Beijing, China.
Department of Medical Laboratory Center, The First Medical Center of Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
Scand J Clin Lab Invest. 2023 Apr;83(2):79-85. doi: 10.1080/00365513.2023.2168566. Epub 2023 Jan 23.
Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis. Thrombomodulin(TM)-modified thrombin generation is a promising laboratory method to detect the thrombotic tendency and prothrombotic phenotype. 141 women were enrolled: 30 healthy non-pregnant controls, 85 healthy pregnant women (26 in 1st trimester, 28 in 2nd trimester, 31 in 3rd trimester), and 26 patients with gestational diabetes mellitus (GDM). Thrombin generation was measured using platelet poor plasma (PPP) TM + and PPP TM- reagents. The parameters were endogenous thrombin potential (ETP), Lagtime, Peak Height, time to peak and ETP ratio(ETP(TM+)/ETP(TM-)). Protein S-depleted plasma samples with different activity were prepared and measured. Pregnancy was associated with a significant decrease of ETP in the presence of TM, compared with that found in the absence of TM. This was observed in all trimesters (1st trimester 1185.67 ± 284.95 nMmin vs.1510.39 ± 281.90 nMmin, < .001; 2nd trimester 1458.96 ± 349.65 nMmin vs. 1929.10 ± 316.98 nMmin, < .001; 3rd trimester 1391.60 ± 317.05 nMmin vs. 1854.88 ± 327.60 nMmin, < .001). The ETP ratio was also markedly increased in all trimesters (0.78 ± 0.10, 0.76 ± 0.11 and 0.74 ± 0.12) compared with that of non-pregnant controls (0.51 ± 0.17, < .001). The results of ETP ratio in protein S-depleted plasmas were 0.986, 0.943 and 0.880 with 0%, 16% and 40% of protein S activity, which indirect represented the thrombotic phenotype of PS deficiency in pregnancy. TM-modified thrombin generation serves as a useful test for hypercoagulation in pregnant women. The ETP ratio and the reference range of ETP in the presence of TM could provide the basis to predict the risk of thrombotic complications during pregnancy.
妊娠是一种高凝状态，与静脉血栓形成风险增加相关。血栓调节蛋白（TM）修饰的凝血酶生成是一种很有前景的实验室方法，用于检测血栓形成倾向和促血栓形成表型。研究纳入了141名女性：30名健康非妊娠对照者、85名健康孕妇（孕早期26名、孕中期28名、孕晚期31名）以及26名妊娠期糖尿病（GDM）患者。使用贫血小板血浆（PPP）TM +和PPP TM -试剂测量凝血酶生成。参数包括内源性凝血酶潜力（ETP）、延迟时间、峰值高度、达到峰值的时间以及ETP比率（ETP（TM +）/ETP（TM -））。制备并测量了具有不同活性的蛋白S缺乏血浆样本。与不存在TM时相比，妊娠在存在TM的情况下与ETP显著降低相关。在所有孕期均观察到这种情况（孕早期1185.67±284.95 nMmin vs.1510.39±281.90 nMmin，<.001；孕中期1458.96±349.65 nMmin vs. 1929.10±316.98 nMmin，<.001；孕晚期1391.60±317.05 nMmin vs. 1854.88±327.60 nMmin，<.001）。与非妊娠对照者相比，所有孕期的ETP比率也显著升高（分别为0.78±0.10、0.76±0.11和0.74±0.12）（0.51±0.17，<.001）。蛋白S缺乏血浆中ETP比率的结果分别为0.986、0.943和0.880，蛋白S活性分别为0%、16%和40%，这间接代表了妊娠中PS缺乏的血栓形成表型。TM修饰的凝血酶生成可作为检测孕妇高凝状态的有用试验。ETP比率以及存在TM时ETP的参考范围可为预测妊娠期间血栓形成并发症的风险提供依据。
