Hyperfibrinolysis
Conditions
Keywords
Hyperfibrinolysis, Pregnant women at term, Tranexamic acid
Brief summary
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.
Detailed 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.
Interventions
PROCEDUREBlood sampling (pregnant)
5.4 ml of venous blood will be taken during the delivery or the caesarian procedure, in addition to the standard of care blood sampling. This blood vial will be sent to the coagulation laboratory and all tests will be performed in vitro. The blood sample will be split in several aliquots. In each blood sample, fibrinolysis will be activated by the plasminogen tissular activator (tPA - concentration: 1066 UtPA/ml). Tranexamic acid will be added at increasing concentrations (2.5 microg/ml up to 40 microg/ml) to each sample and coagulation will be measured by two different tests: EXTEM and NATEM.
PROCEDUREBlood sampling (non pregnant)
5.4 ml of venous blood will be taken. This blood vial will be sent to the coagulation laboratory and all tests will be performed in vitro. The blood sample will be split in several aliquots. In each blood sample, fibrinolysis will be activated by the plasminogen tissular activator (tPA - concentration: 1066 UtPA/ml). Tranexamic acid will be added at increasing concentrations (2.5 microg/ml up to 40 microg/ml) to each sample and coagulation will be measured by two different tests: EXTEM and NATEM.
Sponsors
Brugmann University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coagulation (EXTEM) | within 24h of blood collection | Coagulation will be tested using the EXTEM test (test evaluating the extrinsic coagulation pathway after its activation by tissue factor) |
| Coagulation (NATEM) | within 24h of blood collection | Coagulation will be tested using the NATEM test (test evaluating coagulation after startem addition (for recalcification of citrated blood) and without activator addition) |
Countries
Belgium
Outcome results
None listed