THROmbinography in Pregnant Woman and in Vitro Action of Low Molecular Weight HEparin
NCT Number: NCT06575309
Acronym: TROPHE
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Pregnant Women|Venous Thromboembolic Disease
Interventions: BIOLOGICAL: Blood test
Sponsor: University Hospital, Clermont-Ferrand
Sex: FEMALE
Age: ADULT
Enrollment: 50
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09
Completion Date: 2027-05
Locations: CHU de Clermont-Ferrand, Clermont-Ferrand, 63000, France

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.

Primary Outcome Measures: The endogenous thrombin potential, 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., through study completion, an average of 1 year
Secondary Outcome Measures: The lag time, This is the latency time before the start of thrombin generation (in min).Inhibition of lag time by LMWH is expressed as the inhibition ratio: (basal lag time - lag time with LMWH)/basal lag time., through study completion, an average of 1 year|the peak Height, This is the maximum thrombin concentration (in nM thrombin) (Cmax). Inhibition of this concentration by LMWH is expressed as the inhibition ratio: (basal peak heigh - peak heigh with LMWH)/basal peak heigh., through study completion, an average of 1 year|The time to peak, This is the time after which the maximum amount of thrombin is reached (in min). Inhibition of time to peak by LMWH is expressed as an inhibition ratio: (basal Time to peak - Time to peak with LMWH)/basal Time to peak., through study completion, an average of 1 year|The start tail, This is time after which no more thrombin is generated (in min). Inhibition of start tail by LMWH is expressed as an inhibition ratio: (basal start tail - start tail with LMWH)/basal start tail., through study completion, an average of 1 year|The "velocity index", This is the thrombin generation rate (in nM.min). Inhibition of velocity index by LMWH is expressed as an inhibition ratio: (basal velocity index - velocity index with LMWH)/basal veocity index, through study completion, an average of 1 year