Thrombin generation and low-molecular-weight heparin prophylaxis in pregnant women with thrombophilia

Abstract

Pregnancy is associated with increased risk of venous thromboembolism, especially in the presence of thrombophilia. However, there is no consensus on the optimal approach for thromboprophylaxis in this population. Recent evidence suggests that thrombin generation correlates with the overall procoagulant state of the plasma. Our aim was to evaluate thrombin generation in a prospective cohort of thrombophilic pregnant women, and investigate the effectiveness of low-molecular-weight heparin (LMWH) prophylaxis in pregnancy. Women with severe (n=8), mild (n=47) and no (n=15) thrombophilia were followed throughout their pregnancies. Thrombin generation was evaluated in each trimester as well as five days and eight weeks postpartum (as a reference category). In women undergoing LMWH prophylaxis, thrombin generation and anti-Factor-Xa activity were measured just before and 4 hours after administration (peak effect). Thrombin generation was determined using Technothrombin TGA assay system. For the analysis, median peak thrombin and endogenous thrombin potential were used. Peak thrombin and endogenous thrombin potential were increased during pregnancy compared to the non-pregnant state with the highest results in the severe thrombophilia group. In women receiving LMWH prophylaxis a decrease was observed in thrombin generation at peak effect but over the progression of pregnancy the extent of this decrease reduced in a stepwise fashion. Our results show that thrombin generation demonstrates the hypercoagulable state in thrombophilic pregnancies. In addition, we found the effect of LMWH prophylaxis to progressively decrease with advancing stages of pregnancy.

Effects of Low-Molecular Heparin on Pregnant Women with Factor V Mutation (GA Genotype)

“…Previously, it was shown that the very course of pregnancy is accompanied by an increase in the haemostatic potential, including thrombin potential [44][45][46][47]. The present work, like the study of Selmeczi A et al, revealed not only a bigger increase in thrombin generation during pregnancy in FVL (1691) GA women (compared to the FVL (1691) GG genotype), but also a decrease in thrombin generation due to heparin prophylaxis [48]. In particular, suppression of thrombin generation by LMWH in comparison to the absence of heparin prophylaxis determined from 22 weeks of gestation, including median and peak thrombin was by 9.0% (p =0.0083) and ETP by 4.0% (p =0.0042).…”

Classic and Global Hemostasis Testing in Pregnancy and during Pregnancy Complications

“…Both peak thrombin and ETP were increased over the course of pregnancy compared with the nonpregnant state (8 weeks postpartum) in women with mild thrombophilia (women with heterozygosity for FVL or Prothrombin 20120A mutation and/or a positive history for VTE and/or a positive family history for VTE) as well as those with no thrombophilia. 179 On the contrary, other authors demonstrated that the ETP remained unchanged in both women with and without FVL at all time points (12th, 22nd, and 34th gestational weeks as well as 3 months after delivery). 106 Parameters of TEG "r," "k," and TMA increased while α-angle decreased in patients with inherited thrombophilia as compared with controls.…”

Coagulation challenges in pregnancy: from thrombophilia involvement and management to the utility of thrombin generation monitoring

“…But two parameters of thrombin generation -peak thrombin and endogenous thrombin potential -were higher in pregnant women compared to non-pregnant women, especially in those with severe thrombophilia. The peak of thrombin generation was lower in women who received low molecular weight heparin as prophylaxis, but this effect diminished with the progression of pregnancy [4].…”

“…The hypercoagulable state of pregnant women is associated with anatomic and physiologic changes that occur during pregnancy [3]. The risk of venous thromboembolism is higher especially in thrombophilic pregnant patients [4] and in females with a low birth weight newborn or stillbirth [3]. The classical assays used to explore the coagulation state are inadequate for estimating the thrombotic risk.…”

“…Global assays (including thrombin generation or thrombelastography) can better evaluate the thrombotic risk [5]. More and more evidence has found that overall plasma hypercoagulability is correlated with thrombin generation [4]. Plasma thrombin levels are higher during pregnancy [1].…”