Use of thrombomodulin-modified thrombin generation in uncomplicated pregnancy: the normal range and prothrombotic phenotype

Abstract

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 nM*min vs.1510.39 ± 281.90 nM*min, p < .001; 2nd trimester 1458.96 ± 349.65 nM*min vs. 1929.10 ± 316.98 nM*min, p < .001; 3rd trimester 1391.60 ± 317.05 nM*min vs. 1854.88 ± 327.60 nM*min, p < .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, p < .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.