Use of tranexamic acid to reduce blood loss and associated complications during hysterectomy

Kolodina M.I., Titova M.S., Lyashenko A.S., Lyashenko E.N.

1) Institute “S.I. Georgievsky Medical Academy, V.I. Vernadsky Crimean Federal University, Simferopol, Russia; 2) City Polyclinic No. 17, Saint Petersburg, Russia
This literature review is aimed at summarizing the results of using tranexamic acid (TA), its benefit and safety in practice during hysterectomy. The scientific papers available in the PubMed, MEDLINE, Embase, eLIBRARY, CyberLeninka, and Google Scholar were systematically sought using the search terms “hysterectomy”, “tranexamic acid”, and “use of tranexamic acid during surgical operations” are analyzed. The authors have analyzed six investigations involving 193 616 patients. Hysterectomy belongs to common operations performed in surgical gynecology in the most countries of the world. To reduce blood loss and to prevent possible complications, various mechanical and pharmacological methods are applied. These include the use of TA that a synthetic derivative of lysine and included by the World Health Organization (WHO) into the list of essential medicines. Due to the local and systemic hemostatic effect, this substance is used in bleeding, in the pathogenesis of which a role is played by enhanced fibrinolysis. Fibrinolysis is pharmacologically inhibited by the capacity of TA to link to the binding sites in the molecule of plasmin and so to break its interaction with fibrin and other substrates. TA is well tolerated; its adverse reactions include nausea, vomiting, diarrhea, and allergy; orthostatic collapse is rarely seen. The literature has described the effective use of this agent to reduce blood loss, which finally decreases the need for transfusion and death rates in the patients.
Conclusion: The results of the analysis made by the authors point to the safety and efficacy of TA. Nevertheless, it is necessary to conduct further investigations to confirm these results in a larger number of patients for the more effective application of this substance.

Authors' conclusions: Titova M.S., Kolodina M.I. – concept of the article, material collection, processing, analysis, writing the text; Titova M.S., Kolodina M.I., Lyashenko A.S. – editing; Lyashenko E.N., Lyashenko A.S. – approval of the final version of the article.
Conflicts of interest: The authors declare there are no conflicts of interest.
Funding: The investigation has not been sponsored.
For citation: Kolodina M.I., Titova M.S., Lyashenko A.S., Lyashenko E.N. Use of tranexamic acid to reduce blood loss and associated complications during hysterectomy.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (5): 140-145 (in Russian)
https://dx.doi.org/10.18565/aig.2022.312

Keywords

tranexamic acid
hysterectomy
bleeding during hysterectomy
use of tranexamic acid in bleeding
bleeding

References

  1. Бивалькевич В.А. Медицинская реабилитация женщин репродуктивного возраста после гистерэктомии. Вестник совета молодых ученых и специалистов Челябинской области. 2018; т.3: [1(20)]: 3-6. [Bivalkevich V.A. Medical rehabilitation of women of reproductive age after hysterectomy. Bulletin of the Council of Young Scientists and Specialists of the Chelyabinsk region. 2018; vol.3: [1(20)]: 3-6. 1(20). (in Russian)].
  2. Фролова Н.И., Белокриницкая Т.Е., Баркан Т.М., Голыгин Е.В., Лига В.Ф., Плетнева В.А., Плоткин И.Б., Потапова Е.Н., Тарбаева Д.А., Хавень Т.В., Фалько Е.В., Шемякина К.Н. Медико-социальная характеристика женщин молодого фертильного возраста, перенесших гистерэктомию. Acta Biomedica Scientifica. 2018; 3(4): 15-20. [Frolova N.I., Belokrinitskaya T.E., Barkan T.M., Golygin E.V., Liga V.F., Pletneva V.A., Plotkin I.B., Potapova E.N., Tarbaeva D.A., Khaven T.V., Falko E.V., Shemyakina K.N. Medical and social characteristics of women of young reproductive age after hysterectomy. Acta Biomedica Scientifica. 2018; 3(4): 15-20. (in Russian)]. https://dx.doi.org/10.29413/ABS.2018-3.4.2.
  3. Khazaei Z., Goodarzi E., Sohrabivafa M., Naemi H., Mansori K. Association between the incidence and mortality rates for corpus uteri cancer and human development index (HDI): a global ecological study. Obstet. Gynecol. Sci. 2020; 63(2): 141-9. https://dx.doi.org/10.5468/ogs.2020.63.2.141.
  4. Clarke-Pearson D.L., Geller E.J. Complications of hysterectomy. Obstet. Gynecol. 2013; 121(3): 654-73. https://dx.doi.org/10.1097/AOG.0b013e3182841594.
  5. Nivedhana A.P., Jalakandan B., Gunaseelan S. Effect of prophylactic tranexamic acid on blood conservation in Indian women undergoing abdominal hysterectomy. Int. J. Reprod. Contracept. Obstet. Gynecol. 2018; 7(9): 3538-46. https://dx.doi.org/10.18203/2320-1770.ijrcog20183415.
  6. Hansen C.T., Møller C., Daugbjerg S., Utzon J., Kehlet H., Ottesen B. Establishment of a national Danish hysterectomy database: preliminary report on the first 13,425 hysterectomies. Acta Obstet. Gynecol. Scand. 2008; 87(5): 546-57. https://dx.doi.org/10.1080/00016340802011579.
  7. Topsoee M.F., Bergholt T., Ravn P., Schouenborg L., Moeller C., Ottesen B. et al. Anti-hemorrhagic effect of prophylactic tranexamic acid in benign hysterectomy-a double-blinded randomized placebo-controlled trial. Am. J. Obstet. Gynecol. 2016; 215(1): 72.e1-8. https://dx.doi.org/10.1016/j.ajog.2016.01.184.
  8. Koh M.B., Hunt B.J. The management of perioperative bleeding. Blood Rev. 2003; 17: 179-85. https://dx.doi.org/10.1016/S0268-960X(02)00062-0.
  9. Накопия В.Б., Каземирский А.В., Преображенский П.М., Рябинин М.В. Возможности использования транексамовой кислоты при эндопротезировании коленного сустава. Современные проблемы науки и образования. 2019; 6. [Nakopia V.B., Kazemirsky A.V., Preobrazhensky P.M., Ryabinin M.V. Possibilities of using tranexamic acid in endoprosthesis of the knee joint. Modern Problems of Science and Education. 2019; 6. (in Russian)]. https://dx.doi.org/10.17513/spno.29485.
  10. Доброхотова Ю.Э., Джохадзе Л.С. Применение транексамовой кислоты для профилактики кровотечения в раннем послеродовом периоде. РМЖ. Мать и дитя. 2019; 1: 34-8. [Yu.E. Dobrokhotova, L.S. Djokhadze. Tranexamic acid to prevent early postpartum hemorrhages. Russian Journal of Woman and Child Health. 2019; (1): 34-8. (in Russian)]. https://dx.doi.org/10.32364/2618-8430-2019-2-1-34-38.
  11. Добровольский Ф. Целесообразность профилактического применения транексамовой кислоты в хирургической практике. Вестник экстренной медицины. 2017; 3: 83-7. [Dobrovolsky F. Expedience of the profilactic use of tranexamic acid in surgical practice. Bulletin of Emergency Medicine. 2017;(3): 83-7. (in Russian)].
  12. Cai J., Ribkoff J., Olson S., Raghunathan V., Al-Samkari H., DeLoughery T.G. et al. The many roles of tranexamic acid: an overview of the clinical indications for TXA in medical and surgical patients. Eu. J. Haematol. 2020; 104(2): 79-87. https://dx.doi.org/10.1111/ejh.13348.
  13. Wong J., George R.B., Hanley C.M., Saliba C., Yee D.A., Jerath A. Tranexamic acid: current use in obstetrics, major orthopedic, and trauma surgery. Can. J. Anaesth. 2021; 68(6): 894-917. https://dx.doi.org/10.1007/s12630-021-01967-7.
  14. Dunn C.J., Goa K.L. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999; 57(6): 1005-32. https://dx.doi.org/10.2165/00003495-199957060-00017.
  15. Sallam H.F., Shady N.W. Reducing blood loss during abdominal hysterectomy with intravenous versus topical tranexamic acid: a double-blind randomized controlled trial. J. Obstet. Gynaecol. India. 2019; 69: 173-9.https://dx.doi.org/10.1007/s13224-018-1149-x.
  16. Singh D., Bindal J. The effect of prophylactic use of intravenous tranexamic acid in hysterectomy of benign diseases. Int. J. Clin. Obstet. Gynaecol. 2020; 4(3): 93-7. https://dx.doi.org/10.33545/gynae.2020.v4.i3b.583.
  17. Bhutani S., Malik R., Duhan N. Role of intravenous tranexamic acid (TXA) in reducing perioperative blood loss in hysterectomy for benign gynecological conditions. Authorea. September 11, 2020. https://dx.doi.org/10.22541/au.159986276.65428056.
  18. Gerdessen L., Meybohm P., Choorapoikayil S., Herrmann E., Taeuber I., Neef V. et al. Comparison of common perioperative blood loss estimation techniques: a systematic review and meta-analysis. J. Clin. Monit. Comput. 2021; 35(2): 245-58. https://dx.doi.org/10.1007/s10877-020-00579-8.
  19. Thompson J.D., Birch H.W. Indications of hysterectomy. Clin. Obstet. Gynecol. 1981; 24(4): 1245-58. https://dx.doi.org/10.1097/00003081-198112000-00020.
  20. Discepola F., Valenti D.A., Reinhold C., Tulandi T. Analysis of arterial blood vessels surrounding the myoma: relevance to myomectomy. Obstet. Gynecol. 2007; 110(6): 1301-3. https://dx.doi.org/10.1097/01.AOG.0000290331.95709.26.
  21. Chen C.L., Xu Y.J., Liu P., Zhu J.H., Ma B., Zeng B.L. et al. Characteristics of vascular supply to uterine leiomyoma: an analysis of digital subtraction angiography imaging in 518 cases. Eur. Radiol. 2013; 23(3): 774-9.https://dx.doi.org/10.1007/s00330-012-2643-7.
  22. Dockeray C.J., Sheppard B.L., Daly L., Bonnar J. The fibrinolytic enzyme system in normal menstruation and excessive uterine bleeding and the effect of tranexamic acid. Eur. J. Obstet. Gynecol. Reprod. Biol. 1987; 24(4): 309-18. https://dx.doi.org/10.1016/0028-2243(87)90156-0.
  23. Gleeson N.C. Cyclic changes in endometrial tissue plasminogen activator and plasminogen activator inhibitor type 1 in women with normal menstruation and essential menorrhagia. Am. J. Obstet. Gynecol. 1994; 171(1): 178-83.https://dx.doi.org/10.1016/0002-9378(94)90466-9.
  24. Калинин Р.Е., Сучков И.А., Базаев С.Б., Крылов А.A. Локальные гемостатические средства в хирургической практике. Журнал им. Н.В. Склифосовского «Неотложная медицинская помощь». 2021; 10(2): 337-46. [Kalinin R.E., Suchkov I.A., Bazaev S.B., Krylov A.A. Local hemostatic agents in surgical practice. Russian Sklifosovsky Journal "Emergency Medical Care". 2021; 10(2): 337-46. (in Russian)]. https://dx.doi.org/10.23934/2223-9022-2021-10-2-337-346.
  25. Levy J.H., Tanaka K.A. Prohemostatic agents to prevent perioperative blood loss. Semin. Thromb. Hemost. 2008; 34(5): 439-44.https://dx.doi.org/10.1055/s-0028-1092873.
  26. Samudrala S. Topical hemostatic agents in surgery: a surgeon's perspective. AORN J. 2008; 88(3): S2-11. https://dx.doi.org/10.1016/S0001-2092(08)00586-3.
  27. Fraser I.S., Porte R.J., Kouides P.A., Lukes A.S. A benefit-risk review of systemic haemostatic agents: part 1: in major surgery. Drug Saf. 2008; 31(3): 217-30. https://dx.doi.org/10.2165/00002018-200831030-00003.
  28. Schneeweiss S., Walker A.M., Seeger J.D. Effect of aprotinin on renal dysfunction. Lancet. 2008; 372(9632): 26; author reply 26-7. https://dx.doi.org/10.1016/S0140-6736(08)60980-0.
  29. Schloss B., Gulati P., Yu L., Abdel-Rasoul M., O'Brien W., Visger J.V., Awad H. Impact of aprotinin and renal function on mortality: a retrospective single center analysis. J. Cardiothorac. Surg. 2011; 6: 103. https://dx.doi.org/10.1186/1749-8090-6-103.
  30. Осипова Н.А., Эльдарханов Д.Р., Хороненко В.Э., Хованская Т.П., Петрова В.В., Алексеев Б.Я. Ингибиторы фибринолиза транексамовая кислота и апротинин при радикальной простатэктомии: проспективное рандомизированное сравнительное исследование. Анестезиология и реаниматология. 2012; 5: 35-41. [Osipova N.A., Eldarkhanov D.R., Khoronenko V.E., Khovanskaya T.P., Petrova V.V., Alekseev B.Ya. Fibrinolysis inhibitors tranexamic acid and aprotinine: prospective randomized comparative study. Anesthesiology and Intensive Care. 2012; (5): 35-41. (in Russian)].
  31. Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs. 1985; 29(3): 236-61. https://dx.doi.org/10.2165/00003495-198529030-00003.
  32. Фаткуллин И.Ф., Милова И.А. Принципы и методы уменьшения кровопотери и профилактики кровотечений при операции кесарева сечения. Практическая медицина. 2010; 4: 49-51. [Fatkullin I.F., Milova I.A. Principles and methods in reducing blood loss and prevention of bleeding at caesarean section. Practical Medicine. 2010; (4): 49-51.(in Russian)].
  33. Bellos I., Pergialiotis V. Tranexamic acid for the prevention of postpartum hemorrhage in women undergoing cesarean delivery: an updated meta-analysis. Am. J. Obstet. Gynecol. 2022; 226(4): 510-23.e22. https://dx.doi.org/10.1016/j.ajog.2021.09.025.
  34. Koh A., Adiamah A., Gomez D., Sanyal S. Safety and efficacy of tranexamic acid to minimise perioperative bleeding in hepatic surgery: a systematic review and meta-analysis. World J. Surg. 2022; 46(2): 441-9. https://dx.doi.org/10.1007/s00268-021-06355-2.
  35. Chan C.C., Chan Y.Y., Tanweer F. Systematic review and meta-analysis of the use of tranexamic acid in tonsillectomy. Eur. Arch. Otorhinolaryngol. 2013; 270(2): 735-48. https://dx.doi.org/10.1007/s00405-012-2184-3.
  36. Hu M., Liu Z.B., Bi G. Efficacy and safety of tranexamic acid in orthopaedic trauma surgery: a meta-analysis. Eur. Rev. Med. Pharmacol. Sci. 2019; 23(24): 11025-31. https://dx.doi.org/10.26355/eurrev_201912_19810.
  37. Kim D.H., Kim S., Kang H., Jin H.J., Hwang S.H. Efficacy of tranexamic acid on operative bleeding in endoscopic sinus surgery: a meta-analysis and systematic review. Laryngoscope. 2019; 129(4): 800-7. https://dx.doi.org/10.1002/lary.27766.
  38. Ma Q.M., Han G.S., Li B.W., Li X.J., Jiang T. Effectiveness and safety of the use of antifibrinolytic agents in total-knee arthroplasty: a meta-analysis. Medicine (Baltimore). 2020; 99(20): e20214. https://dx.doi.org/10.1097/MD.0000000000020214.
  39. Murji A., Lam M., Allen B., Richard L., Shariff S.Z., Austin P.C. et al. Risks of preoperative anemia in women undergoing elective hysterectomy and myomectomy. Am. J. Obstet. Gynecol. 2019; 221(6): 629.e1-629.e18.https://dx.doi.org/10.1016/j.ajog.2019.07.018.
  40. Rock W.A. Jr, Meeks G.R. Managing anemia and blood loss in elective gynecologic surgery patients. J, Reprod, Med. 2001; 46 (5, Suppl.): 507-14.
  41. Rawn J. The silent risks of blood transfusion. Curr. Opin. Anaesthesiol. 2008; 21(5): 664-8. https://dx.doi.org/10.1097/ACO.0b013e32830f1fd1.
  42. Jain S.B., Shikha. Decline in blood loss with use of tranexamic acid in cases of hysterectomy: a retrospective observational study in a teaching hospital of central India. Indian J. Obstet. Gynecol. Res. 2021; 8(1): 26-30.https://dx.doi.org/10.18231/j.ijogr.2021.005.
  43. Сармулдаева Ш.К., Нугманова Ж.М., Имангалиева Н.М., Абдикаримова Р.Б., Лежебокова Э.А. Эффективность транексамовой кислоты для снижения кровопотери при кесаревом сечении. Вестник АГИУВ. 2016; 2: 38-43. [Sarmuldaeva Sh.K., Nugmanova Zh.M., Imangalieva N.M., Abdikarimova R.B., Lezhebokova E.A. Efficacy of tranexamic acid to reduce blood loss during caesarean section. Vestnik AGIUV. 2016; (2): 38-43.(in Russian)].
  44. Taeuber I., Weibel S., Herrmann E., Neef V., Schlesinger T., Kranke P. et al. Association of intravenous tranexamic acid with thromboembolic events and mortality: a systematic review, meta-analysis, and meta-regression. JAMA Surg. 2021; 156(6): e210884. https://dx.doi.org/10.1001/jamasurg.2021.0884.
  45. Xu J.W., Qiang H., Li T.L., Wang Y., Wei X.X., Li F. Efficacy of topical vs intravenous tranexamic acid in reducing blood loss and promoting wound healing in bone surgery: a systematic review and meta-analysis. World J. Clin. Cases. 2021; 9(17): 4210-20. https://dx.doi.org/10.12998/wjcc.v9.i17.4210.
  46. Teoh W.Y., Tan T.G., Ng K.T., Ong K.X., Chan X.L., Hung Tsan S.E. et al. Prophylactic topical tranexamic acid versus placebo in surgical patients: a systematic review and meta-analysis. Ann. Surg. 2021; 273(4): 676-83.https://dx.doi.org/10.1097/SLA.0000000000003896.
  47. Gayet-Ageron A., Prieto-Merino D., Ker K., Shakur H., Ageron F.X., Roberts I.; Antifibrinolytic Trials Collaboration. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet. 2018; 391(10116): 125-32. https://dx.doi.org/10.1016/S0140-6736(17)32455-8.
  48. Бобовник С.В., Буланов А.Ю., Григорьев Е.В., Заболотских И.Б., Лебединский К.М., Синьков С.В., Шень Н.П., Щеголев А.В. Протокол реанимации и интенсивной терапии при острой массивной кровопотере. Федеральные клинические рекомендации по ведению больных. М.; 2018. 42с. [Bobovnik S.V., Bulanov A.Y., Grigoryev E.V., Zabolotskikh I.B., Lebedinsky K.M., Sinkov S.V., Shen N.P., Shchegolev A.V. Resuscitation and intensive care protocol for acute massive blood loss. Federal clinical guidelines on the management of patients. Мoscow; 2018. 42p. (in Russian)].
  49. 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): 2105-16. https://dx.doi.org/10.1016/S0140-6736(17)30638-4.

Received 23.12.2022

Accepted 15.05.2023

About the Authors

Maria I. Kolodina, 6th year student of the 2nd Faculty of Medicine, Institute "S.I. Georgievsky Medical Academy", V.I. Vernadsky Crimean Federal University,
295051, Russia, Republic of Crimea, Simferopol, Lenin Boulevard, 5/7, kolodinamariauvanovna@mail.ru, https://orcid.org/0000-0002-5478-5101
Margarita S. Titova, 5th year student of the 2nd Faculty of Medicine, Institute "S.I. Georgievsky Medical Academy", V.I. Vernadsky Crimean Federal University,
295051, Russia, Republic of Crimea, Simferopol, Lenin Boulevard, 5/7, +7(978)895-97-98, titova.margo00@mail.ru, https://orcid.org/0000-0002-4476-0955
Anastasia S. Lyashenko, therapist, City Polyclinic No. 17, 195176, Russia, St. Petersburg, Metallistov Ave., 56, grobovaya98@mail.ru,
https://orcid.org/0000-0002-0284-7649
Elena N. Lyashenko, PhD, Associate Professor at the Department of Obstetrics and Gynecology No. 2, Institute "S.I. Georgievsky Medical Academy", V.I. Vernadsky
Crimean Federal University, 295051, Russia, Republic of Crimea, Simferopol, Lenin Boulevard, 5/7, helen.lyashen@mail.ru, https://orcid.org/0000-0002-4350-5020
Corresponding author: Margarita S. Titova, titova.margo00@mail.ru

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.