Thromb Haemost 2022; 122(11): 1869-1878
DOI: 10.1055/s-0042-1755379
Coagulation and Fibrinolysis

Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study

Stéphanie Roullet
1   Pôle d'Anesthésie-Réanimation, CHU Bordeaux, Bordeaux, France
2   INSERM, Biologie des Maladies Cardiovasculaires, University of Bordeaux, U1034, Pessac, France
,
Timothée Rivoire
1   Pôle d'Anesthésie-Réanimation, CHU Bordeaux, Bordeaux, France
,
Clémence Houssin
3   Département de Gynécologie et Obstétrique, CHU Bordeaux, Bordeaux, France
,
Sylvie Labrouche
2   INSERM, Biologie des Maladies Cardiovasculaires, University of Bordeaux, U1034, Pessac, France
4   Laboratoire d'hématologie, CHU Bordeaux, Bordeaux, France
,
Sandrine Paquin
1   Pôle d'Anesthésie-Réanimation, CHU Bordeaux, Bordeaux, France
,
Karine Nouette-Gaulain
1   Pôle d'Anesthésie-Réanimation, CHU Bordeaux, Bordeaux, France
5   INSERM, Maladies Rares: Génétique et Métabolisme, University of Bordeaux, Bordeaux, France
,
Catherine Deneux-Tharaux
6   INSERM, Perinatal Obstetrical and Pediatric Epidemiology Research Team (EPOPé), Centre for Research on Epidemiology and Statistics (CRESS), Paris University, Paris, France
,
Jean Amiral
7   SH-Consulting, Andrésy, France
,
Chloé James
2   INSERM, Biologie des Maladies Cardiovasculaires, University of Bordeaux, U1034, Pessac, France
4   Laboratoire d'hématologie, CHU Bordeaux, Bordeaux, France
,
Loïc Sentilhes
3   Département de Gynécologie et Obstétrique, CHU Bordeaux, Bordeaux, France
› Author Affiliations
Funding This study was funded by the Bordeaux Association for Training and Research in Obstetrics and Gynecology (ABFREGO) and by the Anesthesiologist Association in Vascular and Transplantation Surgery (AARCVT). The funding sources had no role in the design of this study, the collection, analysis or interpretation of data, the writing of this report, or in the decision to submit this article for publication.


Abstract

Background Fibrinolysis activation during delivery contributes to postpartum hemorrhage (PPH). Clot lysis time studied with the global fibrinolytic capacity device (GFC/LT) is a functional test which rapidly assesses fibrinolytic profile. Tranexamic acid (TXA) is an efficient antifibrinolytic therapy.

Methods We prospectively studied fibrinolysis and coagulation in 33 women included in the TRAAP2 trial, which aimed to assess the impact of TXA in preventing PPH following a cesarean delivery. TXA or placebo was randomly administered after childbirth as part of the TRAAP2 trial's protocol. Fibrinolytic (GFC/LT, plasma concentration of fibrinolysis activators and inhibitors) and hemostatic parameters were assayed at three sample times (TREF [T-reference] after anesthesia, T15 and T120minutes after TXA, or placebo administration).

Results All cesarean deliveries were elective. In the placebo group, the clot lysis time assessed with GFC/LT significantly decreased between TREF and T120, indicating an activated fibrinolysis (44 [interquartile range, IQR: 40–48] vs. 34 [IQR: 30–36] minutes, p<0.001). In both TXA and placebo groups, significant fluctuations of the plasmatic concentrations of fibrinolytic mediators were noticed over time, suggesting fibrinolysis activation. Clot lysis time measured by GFC/LT was significantly increased in women of the TXA group as compared with those in the placebo group at T15 (120 [120–120] vs. 36 [34–41] minutes, p<0.001) and T120minutes (113 [99–120] vs. 34 [30–36] minutes, p<0.001) after drug administration, indicating a decreased in fibrinolysis in those women.

Conclusion GFC/LT evidenced fibrinolysis activation during cesarean delivery, linked to a decrease in fibrinolytic inhibitors. GFC/LT revealed a significant antifibrinolytic effect of TXA compared with placebo.

Author Contributions

S.R. designed the study, collected data, analyzed data, and wrote the manuscript. T.R. collected data, analyzed data, and wrote the manuscript. C.H. and S.P. collected data. S.L. analyzed data. K.N.-G. and C.D.T. provided important intellectual input. J.A. collected and analyzed data. C.J. contributed to the study design. L.S. designed the study and wrote the manuscript. All authors reviewed and edited the manuscript and approved the final version.




Publication History

Received: 27 December 2021

Accepted: 25 June 2022

Article published online:
08 September 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Sentilhes L, Vayssière C, Deneux-Tharaux C. et al. Postpartum hemorrhage: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF): in collaboration with the French Society of Anesthesiology and Intensive Care (SFAR). Eur J Obstet Gynecol Reprod Biol 2016; 198: 12-21
  • 2 Callaghan WM, Kuklina EV, Berg CJ. Trends in postpartum hemorrhage: United States, 1994-2006. Am J Obstet Gynecol 2010; 202 (04) 353.e1-353.e6
  • 3 Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet 2006; 367 (9516): 1066-1074
  • 4 Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost 2003; 29 (02) 125-130
  • 5 Shimada H, Takashima E, Soma M. et al. Source of increased plasminogen activators during pregnancy and puerperium. Thromb Res 1989; 54 (02) 91-98
  • 6 Solomon C, Collis RE, Collins PW. Haemostatic monitoring during postpartum haemorrhage and implications for management. Br J Anaesth 2012; 109 (06) 851-863
  • 7 Collis RE, Collins PW. Haemostatic management of obstetric haemorrhage. Anaesthesia 2015; 70 (Suppl 1): 78-86
  • 8 Butwick AJ. Postpartum hemorrhage: wherefore art thou, hyperfibrinolysis?. Anesth Analg 2020; 131 (05) 1370-1372
  • 9 Liu Z, Liu C, Zhong M. et al. Changes in coagulation and fibrinolysis in post-cesarean section parturients treated with low molecular weight heparin. Clin Appl Thromb Hemost 2020; 26: 1076029620978809
  • 10 Morikawa M, Yamada T, Turuga N. et al. Coagulation-fibrinolysis is more enhanced in twin than in singleton pregnancies. J Perinat Med 2006; 34 (05) 392-397
  • 11 Shakur H, Roberts I, Fawole B. et al; WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet 2017; 389 (10084): 2105-2116
  • 12 Paul-Brent P-A, Cattley TN, Myers SP, Brooks L, Cheras PA. A rapid microtitre plate screening method for in vitro assessment of fibrinolysis: a preliminary report. Blood Coagul Fibrinolysis 2004; 15 (03) 273-278
  • 13 Glassman A, Abram M, Baxter G, Swett A. Euglobulin lysis times: an update. Ann Clin Lab Sci 1993; 23 (05) 329-332
  • 14 Ilich A, Bokarev I, Key NS. Global assays of fibrinolysis. Int J Lab Hematol 2017; 39 (05) 441-447
  • 15 Snegovskikh D, Souza D, Walton Z. et al. Point-of-care viscoelastic testing improves the outcome of pregnancies complicated by severe postpartum hemorrhage. J Clin Anesth 2018; 44: 50-56
  • 16 Mallaiah S, Barclay P, Harrod I, Chevannes C, Bhalla A. Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage. Anaesthesia 2015; 70 (02) 166-175
  • 17 Collins P, Abdul-Kadir R, Thachil J. Subcommittees on Women' s Health Issues in Thrombosis and Haemostasis and on Disseminated Intravascular Coagulation. Management of coagulopathy associated with postpartum hemorrhage: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (01) 205-210
  • 18 Collins PW, Cannings-John R, Bruynseels D. et al. Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial. Br J Anaesth 2017; 119 (03) 411-421
  • 19 Huissoud C, Carrabin N, Audibert F. et al. Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry. BJOG 2009; 116 (08) 1097-1102
  • 20 Roullet S, Freyburger G, Cruc M. et al. Management of bleeding and transfusion during liver transplantation before and after the introduction of a rotational thromboelastometry-based algorithm. Liver Transpl 2015; 21 (02) 169-179
  • 21 Miszta A, Ahmadzia HK, Luban NLC. et al. Application of a plasmin generation assay to define pharmacodynamic effects of tranexamic acid in women undergoing cesarean delivery. J Thromb Haemost 2021; 19 (01) 221-232
  • 22 Amiral J, Laroche M, Seghatchian J. A new assay for global fibrinolysis capacity (GFC): investigating a critical system regulating hemostasis and thrombosis and other extravascular functions. Transfus Apheresis Sci 2018; 57 (01) 118-126
  • 23 Rijken DC, Hoegee-de Nobel E, Jie AFH, Atsma DE, Schalij MJ, Nieuwenhuizen W. Development of a new test for the global fibrinolytic capacity in whole blood. J Thromb Haemost 2008; 6 (01) 151-157
  • 24 Roullet S, Labrouche S, Mouton C. et al. Lysis timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation. J Clin Pathol 2019; 72 (01) 58-65
  • 25 Sentilhes L, Daniel V, Deneux-Tharaux C. TRAAP2 Study Group and the Groupe de Recherche en Obstétrique et Gynécologie (GROG). TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial - a study protocol. BMC Pregnancy Childbirth 2020; 20 (01) 63
  • 26 Sentilhes L, Sénat MV, Le Lous M. et al; Groupe de Recherche en Obstétrique et Gynécologie. Tranexamic acid for the prevention of blood loss after cesarean delivery. N Engl J Med 2021; 384 (17) 1623-1634
  • 27 Shander A, Javidroozi M, Sentilhes L. Tranexamic acid and obstetric hemorrhage: give empirically or selectively?. Int J Obstet Anesth 2021; 48: 103206
  • 28 Roullet S, Weinmann L, Labrouche S. et al. Fibrinolysis in trauma patients: wide variability demonstrated by the Lysis Timer. Scand J Clin Lab Invest 2019; 79 (1-2): 136-142
  • 29 Runnebaum IB, Maurer SM, Daly L, Bonnar J. Inhibitors and activators of fibrinolysis during and after childbirth in maternal and cord blood. J Perinat Med 1989; 17 (02) 113-119
  • 30 Bremer HA, Brommer EJP, Wallenburg HCS. Effects of labor and delivery on fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1994; 55 (03) 163-168
  • 31 Amiral J, Malmejac A, Gin H. et al. Evaluation of the fibrinolytic potential on plasma: physiological and pathological variations, and associations with cardio-vascular disease risk factors. Fibrinolysis and Proteolysis 1999; 13: 1-10
  • 32 Bonnar J, McNicol GP, Douglas AS. Fibrinolytic enzyme system and pregnancy. BMJ 1969; 3 (5667): 387-389
  • 33 O'Riordan MN, Higgins JR. Haemostasis in normal and abnormal pregnancy. Best Pract Res Clin Obstet Gynaecol 2003; 17 (03) 385-396
  • 34 Ducloy-Bouthors AS, Duhamel A, Kipnis E. et al. Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial. Br J Anaesth 2016; 116 (05) 641-648
  • 35 Shakur-Still H, Roberts I, Fawole B. et al. Effect of tranexamic acid on coagulation and fibrinolysis in women with postpartum haemorrhage (WOMAN-ETAC): a single-centre, randomised, double-blind, placebo-controlled trial. Wellcome Open Res 2018; 3: 100