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Evaluation of the Minimum Concentration of Tranexamic Acid Required to Inhibit Fibrinolysis in a Population of Pregnant Women at Term.

C

CHU Brugmann University Hospital

Status

Completed

Conditions

Hyperfibrinolysis

Treatments

Procedure: Blood sampling (non pregnant)
Procedure: Blood sampling (pregnant)

Study type

Interventional

Funder types

Other

Identifiers

NCT02579941
CHUB-Fibrinolyse

Details and patient eligibility

About

Pregnancy induces a physiological change of hemostasis to a prothrombotic state : protein S decrease and increase of virtually all the clotting factors, in particular fibrinogen, von Willebrand factor and factor VIII. However, a state of hyperfibrinolysis may occur in the immediate postpartum period (especially after placental delivery), thereby promoting postpartum hemorrhage.

This state of hyperfibrinolysis is associated with the use of transfusions of blood products and the realization of hysterectomy.It is currently the most common etiology of maternal mortality in childbirth.There is an imperative to develop an efficient and reliable protocol for the management of this postpartum complication.

Tranexamic acid is an anti-fibrinolytic agent (like lysine) which acts by preventing the conversion of plasminogen to plasmin, by blocking the binding of plasminogen to the heavy chain of fibrin.The optimal dose of tranexamic acid enabling to inhibit fibrinolysis without increasing the complications rate remains to be defined. It is in this context that the investigators aim to evaluate, in an in-vitro model, the minimum dose of tranexamic acid required to inhibit fibrinolysis after activation of the latter by t-PA. The degree of fibrinolysis will be evaluated by thromboelastometry.

Full description

Pregnancy induces a physiological change of hemostasis to a prothrombotic state : protein S decrease and increase of virtually all the clotting factors, in particular fibrinogen, von Willebrand factor and factor VIII. However, a state of hyperfibrinolysis may occur in the immediate postpartum period (especially after placental delivery), thereby promoting postpartum hemorrhage.

This state of hyperfibrinolysis is associated with the use of transfusions of blood products and the realization of hysterectomy.It is currently the most common etiology of maternal mortality in childbirth. Although its incidence is low in western countries, it remains very high in the world.There is an imperative to develop an efficient and reliable protocol for the management of this postpartum complication.

Tranexamic acid is an anti-fibrinolytic agent (like lysine) which acts by preventing the conversion of plasminogen to plasmin, by blocking the binding of plasminogen to the heavy chain of fibrin.The use of this agent has spread in recent years in many types of surgery (cardiac, orthopedic, etc.), and in patient polytrauma. However, the number of studies evaluating its efficacy in the management (treatment and / or prevention) of postpartum hemorrhage is limited. In addition, the doses used are extrapolated from studies of a different population (multiple trauma, cardiac surgery, etc).

The tranexamic acid proposed scheme is currently used is not suitable for the population of pregnant women at term. It was established arbitrarily on the basis of the adult population without considering the physiological and metabolic characteristics of the term pregnancy. The optimal dose of tranexamic acid enabling inhibition of fibrinolysis, without increasing the complications rate, remains thus to be defined.

It is in this context that the investigators aim to evaluate, in an in-vitro model, the minimum dose of tranexamic acid required to inhibit fibrinolysis after activation of the latter by t-PA. The degree of fibrinolysis will be evaluated by thromboelastometry.

Enrollment

40 patients

Sex

Female

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Pregnant women group:

  • pregnant women at term (>37 weeks of gestation)
  • patients admitted for delivery or elective cesarian section
  • written informed consent

Healthy volunteers group:

  • women aged from 18 to 40

Exclusion criteria

  • Dying patients (ASA 5)
  • Jehovah's witnesses
  • Patients with pre-eclampsia, HELLP syndrome, placenta previa or placental abruption.
  • Multiple pregnancy
  • Presence of preoperative coagulation disorders defined as: platelets <150,000 / mm3; PTT <70%; aPTT> 33 sec; fibrinogen <350 mg / dL.
  • Treatment with anticoagulant or antiplatelet agent.

Trial design

Primary purpose

Prevention

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

40 participants in 3 patient groups

Pregnant women at term, vaginal childbirth
Experimental group
Treatment:
Procedure: Blood sampling (pregnant)
Pregnant women at term, cesarean delivery
Experimental group
Treatment:
Procedure: Blood sampling (pregnant)
Female volunteers, age 18 to 40
Experimental group
Treatment:
Procedure: Blood sampling (non pregnant)

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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