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

NCT06575309 | Recruiting

• 2 other identifiers: RBHP 2024 LEBRETON2024-A00109-39
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Pregnant Women; Venous Thromboembolic Disease

Keywords

Thrombography; Pregnancy; Postpartum; Low molecular weight heparins (LMWH)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• The lag time

  through study completion, an average of 1 year

• the peak Height

  through study completion, an average of 1 year

• The time to peak

  through study completion, an average of 1 year

• The start tail

  through study completion, an average of 1 year

• The "velocity index"

  through study completion, an average of 1 year

Study Arms (1)

Pregnant women

Biological: Blood test

Interventions

Blood test BIOLOGICAL

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.

Pregnant women

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Pregnant women with no health problems recruited during their 1st trimester of pregnancy, then monitored throughout the pregnancy.

You may qualify if:

• Normal 1st trimester pregnancy
• Age \> 18

You may not qualify if:

• Coagulation disease (Von Willebrand disease, known coagulation factor deficiency before pregnancy)
• VTE history
• First-degree family history of idiopathic VTE
• Known biological risk factor for thrombosis Inherited deficiencies in coagulation inhibitors (antithrombin, protein C, protein S) Factor V Leiden polymorphism Prothrombin gene 20210G\>A polymorphism Anti-phospholipid antibodies
• Current anticoagulant use (VKA, heparins, etc.)
• Gestational diabetes detected in the 1st trimester
• Pre-existing type 1 and type 2 diabetes
• History of pathological pregnancy Premature delivery Postpartum hemorrhage Preeclampsia
• Hepatopathy
• Obesity (BMI ≥ 30)
• Infections (HIV, HBV, HCV...)
• Autoimmune diseases
• Pregnancy resulting from in vitro fertilization protocol
• Multiple pregnancy
• Patient under guardianship, curatorship or safeguard of justice

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (2)

CHU de Clermont-Ferrand

Clermont-Ferrand, 63000, France

NOT YET RECRUITING

CHU Estaing

Clermont-Ferrand, 63003, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Interventions

Hematologic Tests

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Aurélien Lebreton

  CHU de Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

+33473754963; promo_interne_drci@chu-clermontferrand.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: August 28, 2024
• Study Start: November 21, 2024
• Primary Completion: November 1, 2025
• Study Completion (Estimated): May 1, 2027
• Last Updated: November 26, 2024

Record last verified: 2024-05

Locations

FR (2)