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

NCT02579941 | Completed

• 1 other identifier: CHUB-Fibrinolyse
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperfibrinolysis

Keywords

Hyperfibrinolysis; Pregnant women at term; Tranexamic acid

Outcome Measures

Primary Outcomes (2)

• Coagulation (EXTEM)

  Coagulation will be tested using the EXTEM test (test evaluating the extrinsic coagulation pathway after its activation by tissue factor)

  within 24h of blood collection

• Coagulation (NATEM)

  Coagulation will be tested using the NATEM test (test evaluating coagulation after startem addition (for recalcification of citrated blood) and without activator addition)

  within 24h of blood collection

Study Arms (3)

Pregnant women at term, vaginal childbirth

EXPERIMENTAL

Procedure: Blood sampling (pregnant)

Pregnant women at term, cesarean delivery

EXPERIMENTAL

Procedure: Blood sampling (pregnant)

Female volunteers, age 18 to 40

EXPERIMENTAL

Procedure: Blood sampling (non pregnant)

Interventions

Blood sampling (pregnant) PROCEDURE

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.

Pregnant women at term, cesarean delivery; Pregnant women at term, vaginal childbirth

Blood sampling (non pregnant) PROCEDURE

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.

Female volunteers, age 18 to 40

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brugmann University Hospital: lead

Study Sites (1)

CHU Brugmann

Brussels, 1020, Belgium

Location

Related Publications (8)

• Cerneca F, Ricci G, Simeone R, Malisano M, Alberico S, Guaschino S. Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol. 1997 May;73(1):31-6. doi: 10.1016/s0301-2115(97)02734-6.

  PMID: 9175686 BACKGROUND

• Bonnar J, McNicol GP, Douglas AS. Coagulation and fibrinolytic mechanisms during and after normal childbirth. Br Med J. 1970 Apr 25;2(5703):200-3. doi: 10.1136/bmj.2.5703.200.

  PMID: 5443405 BACKGROUND

• Brenner B. Haemostatic changes in pregnancy. Thromb Res. 2004;114(5-6):409-14. doi: 10.1016/j.thromres.2004.08.004.

  PMID: 15507271 BACKGROUND

• Faraoni D, Carlier C, Samama CM, Levy JH, Ducloy-Bouthors AS. [Efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of post-partum haemorrhage: a systematic review with meta-analysis]. Ann Fr Anesth Reanim. 2014 Nov;33(11):563-71. doi: 10.1016/j.annfar.2014.07.748. Epub 2014 Oct 18. French.

  PMID: 25450729 BACKGROUND

• Sentilhes L, Lasocki S, Ducloy-Bouthors AS, Deruelle P, Dreyfus M, Perrotin F, Goffinet F, Deneux-Tharaux C. Tranexamic acid for the prevention and treatment of postpartum haemorrhage. Br J Anaesth. 2015 Apr;114(4):576-87. doi: 10.1093/bja/aeu448. Epub 2015 Jan 8.

  PMID: 25571934 BACKGROUND

• Ronsmans C, Graham WJ; Lancet Maternal Survival Series steering group. Maternal mortality: who, when, where, and why. Lancet. 2006 Sep 30;368(9542):1189-200. doi: 10.1016/S0140-6736(06)69380-X.

  PMID: 17011946 BACKGROUND

• Ortmann E, Besser MW, Klein AA. Antifibrinolytic agents in current anaesthetic practice. Br J Anaesth. 2013 Oct;111(4):549-63. doi: 10.1093/bja/aet154. Epub 2013 May 9.

  PMID: 23661406 BACKGROUND

• Collis RE, Collins PW. Haemostatic management of obstetric haemorrhage. Anaesthesia. 2015 Jan;70 Suppl 1:78-86, e27-8. doi: 10.1111/anae.12913.

  PMID: 25440400 BACKGROUND

MeSH Terms

Interventions

Blood Specimen Collection; Gravidity

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Pregnancy; Reproduction; Reproductive History; Epidemiologic Factors; Public Health; Environment and Public Health

Study Officials

• Philippe Van der Linden, MD

  CHU Brugmann

  PRINCIPAL INVESTIGATOR

• Arnaud Lechien, MD

  CHU Brugmann

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of clinic

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 20, 2015
• Study Start: November 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 19, 2018

Record last verified: 2018-01

Locations

BE (1)