THROmbinography in Pregnant Woman and in Vitro Action of Low Molecular Weight HEparin

Condition(s) studied

Investigational drug(s) / intervention(s)

Blood test: The procedures added as part of this research are 6 blood samples, the volumes of which do not exceed the volume authorized in the order of February 17, 2021, i.e. 27mL.

Study summary

Pregnancy is associated with major changes affecting all satges of hemostasis. Certain procoagulant factors are increased, such as factors VII, VIII, IX, X, XII, fibrinogen and Von Willebrand factor. Anticoagulant molecules are also affected by pregnancy, notably the protein C - protein S (PC - PS) system. overall, PC activity is little affected by pregnancy, increasing in the 2nd trimester and decreasing in the 3rd, but remaining within normal values. PS decreases from the first trimester of pregnancy, then progressively with gestational age. Antithrombin is stable during pregnancy.

The increased in most coagulation factors, combined with the decrease in concentrations of anticoagulant molecules, creates a state of relative hypercoagulability that protects women from bleeding during homostatic challenge of childbirth, but predisposes them to venous thromboembolic events.

The risk of venous thromboembolism (VTE) during pregnancy is increased compared to non-pregnant women of the same age. The post-partum period is also considered a thrombotic risk state for up to 12 weeks after delivery. Data on the incidence of VTE as a function of gestational age are contradictory: depending on the study, incidence may be stable or increase with advancing pregnancy.

Low-molecular-weight heparin (LMWH) is the anticoagulant treatment of choice for prophylactic or curative treatment of VTE during pregnancy.

Physiological changes during pregnancy may alter the pharmacokinetic properties of LMWH. The increased volume of distribution and higher glomerular filtration rate may result in a reduced anticoagulant effect. On the other hand, the state of hypercoagulability probably counteracts the anticoagulant effect of LMWH. Nevertheless, the need to adjust doses during pregnancy remains controversial, and monitoring of anti-Xa activity is not clearly recommended. The optimal dose of LMWH in pregnant women, for both preventive and curative treatment, remains poorly understood. Initiation of treatment with LMWH therefore requires discussion of the dosage to be administered.

Assessment of anticoagulation using more precise tools than those currently available on a routine basis could be useful in this context.

Thrombinography enables the amount of thrombin generated in the presence of coagulation activators to be assessed over time. This tool can be used to assess the impact of in vitro addition of different doses of LMWH in pregnant versus non-pregnant women and in the postpartum period.

In this pilot study, the investigators propose to evaluate thrombin generation, before and after in vitro addition of LMWH, in pregnant women longitudinally, during the 3 trimesters of pregnancy, postpartum and post-pregnancy.

Eligibility

Primary outcome measure(s)

• The endogenous thrombin potential — through study completion, an average of 1 year
  Thrombinography provides a graphical representation of the amount of thrombin generated as a function of time (thrombinogram). The "endogenous thrombin potential (ETP)" corresponds to the area under the curve, reflecting the overall quantity of thrombin generated (in nM.min-1).LMWH inhibition of PTE is expressed as the inhibition ratio: (basal PTE - PTE with LMWH)/basal PTE.

Trial sites (2)

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