Comparison of the efficacy and safety of aprotinin and tranexamic acid in cardiac surgery with cardiopulmonary bypass in adult patients

The objective was to compare the efficacy and safety of the use of aprotinin and tranexamic acid in cardiac surgery with cardiopulmonary bypass (CPB) in adult patients.

Materials and methods. A randomized prospective comparative study was conducted. A total of 62 patients were included who underwent cardiac surgery with CPB. In order to prevent bleeding, fibrinolysis inhibitors were used intraoperatively in all patients, depending on the drug used, two groups were formed: «tranexamic acid» (n = 32) and «aprotinin» (n = 30). The time of the operation, the time of CPB and anoxia were recorded, postoperative blood loss according to 12-hour intervals and the need for transfusion during and after surgery were assessed. In the postoperative period, the need for inotropic support at the time of transfer to the intensive care unit (inotropic index), time of ALV, kidney (GFR, creatinine) and liver (ALT, direct bilirubin) function, as well as markers of the inflammatory response (white blood cell count, C-RP) were taken into account.

Results. The volume of postoperative blood loss for 12 hours, as well as the need for transfusion in the intraoperative period, did not differ in the studied groups. At the same time, a decrease in the need for erythrocyte suspension was detected in the «aprotinin» group in the early postoperative period (p = 0.02). In the «aprotinin» group, the white blood cell count was higher than in the «tranexamic acid» group (p = 0.02), while the C-RP level was significantly lower in the “aprotinin” group (p = 0.002). The values of the PaO₂ /FiO₂ ratio in the studied groups did not differ, and the time of ALV was significantly lower in the «aprotinin» group (p = 0.016).

Conclusion. The results of the study showed that the use of aprotinin during cardiac surgery with CPB reduces the need for transfusion of hemocomponents in the early postoperative period; no side effects were detected when using the drug.

1. Alderman E. L., Levy J. H., Rich J. B. et al. Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial // J Thorac Cardiovasc Surg. – 1998. – Vol. 116. – P. 716–730. http://doi.org/10.1016/S0022-5223(98)00431-0.

2. Atasever A. G., Eerens M., Van den Eynde R. et al. Efficacy and safety of aprotinin in paediatric cardiac surgery: а systematic review and meta-anal ysis // Eur J Anaesthesiol. – 2022. – Vol. 39, № 4. – P. 352–367. http://doi.org/10.1097/EJA.0000000000001632.

3. Banerjee D., Feng J., Sellke F. W. Strategies to attenuate maladaptive inflammatory response associated with cardiopulmonary bypass // Front Surg. – 2024. – Vol. 3, № 11. – 1224068. http://doi.org/10.3389/fsurg.2024.1224068.

4. Beierlein W., Scheule A. M., Dietrich W. et al. Forty years of clinical aprotinin use: a review of 124 hypersensitivity reactions // Ann Thorac Surg. – 2005. – Vol. 79, № 2. – P. 741–748. http://doi.org/10.1016/j.athoracsur.2004.03.072.

5. Boer C., Meesters M. I., Milojevic M. et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery // J Cardiothorac Vasc Anesth. – 2018. – Vol. 32, № 1. – P. 88–120. http://doi.org/10.1053/j.jvca.2017.06.026.

6. Bohrer H., Fleischer F., Lang J. et al. Early formation of thrombi on pulmonary artery catheters in cardiac surgical patients receiving high-dose aprotinin // J Cardiothorac Anesth. – 1990. – Vol. 4, № 2. – P. 222–225. http://doi.org/10.1016/0888-6296(90)90241-7.

7. De Hert S., Ouattara A., Royston D. et al. Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery // Eur J Anaesthesiol. – 2022. – Vol. 39, № 8. – P. 685–624. http://doi.org/10.1097/EJA.0000000000001710.

8. Dyke C., Aronson S., Dietrich W. et al. Universal deìinition of perioperative bleeding in adult cardiac surgery // Journal of Thoracic and Cardiovascular Surgery. – 2014. – Vol. 147, № 5. – P. 1458–1463. http://doi.org/10.1016/j.jtcvs.2013.10.070.

9. EMA. Antifibrinolytics containing aprotinin, aminocaproic acid and tranexamic acid. Aprotinin. Assessment report. 18 September 2013. URL: https://www.ema.europa.eu/en/documents/referral/assessment-report-anti-fibrinolytic-medicines-aprotinin_en.pdf (accessed: 20.05.2025).

10. Fergusson D. A., Hebert P. C., Mazer C. D. et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery // N Engl J Med. – 2008. – Vol. 358, № 22. – P. 2319–2331. http://doi.org/10.1056/NEJMoa0802395.

11. Gallo E., Gaudard P., Provenchère S. et al. Use of aprotinin versus tranexamic acid in cardiac surgery patients with high-risk for excessive bleeding (APACHE) trial: a multicentre retrospective comparative non-randomized historical study // Eur J Cardiothorac Surg. – 2024. – Vol. 65, № 2. – ezae001. http://doi.org/10.1093/ejcts/ezae001.

12. Gerstein N. S., Brierley J. K., Windsor J. et al. Antifibrinolytic agents in cardiac and noncardiac surgery: a comprehensive overview and update // J Cardiothorac Vasc Anesth. – 2017. – Vol. 31, № 6. – P. 2183–2205. http://doi.org/10.1053/j.jvca.2017.02.029.

13. Gott J. P., Cooper W. A., Schmidt F. E. Jr. et al. Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies // Ann Thorac Surg. – 1998. – Vol. 66, № 3. – P. 747–53. http://doi.org/10.1016/s0003-4975(98)00695-x.

14. Havel M., Grabenwöger F., Schneider J. et al. Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood // J Thorac Cardiovasc Surg. – 1994. – Vol. 107, № 3. – P. 807–810. PMID: 7510351.

15. Henry D. A., Carless P. A., Moxey A. J. et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion // Cochrane Database Syst Rev. – 2007. – Vol. 17, № 4. – P. CD001886. http://doi.org/10.1002/14651858.CD001886.pub2.

16. Huang H., Ding W., Su Z. et al. Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery // J Thorac Cardiovasc Surg. – 1993. – Vol. 106, № 1. – P. 11–18. PMID: 7686594.

17. Hunt B. J., Parratt R. N., Segal H. C. et al. Activation of coagulation and fibrinolysis during cardiothoracic operations // Ann Thorac Surg. – 1998. – Vol. 65, № 3. – P. 712–718. http://doi.org/10.1016/s0003-4975(97)01345-3.

18. Karkouti K., Beattie W. S., Dattilo K. M. et al. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery // Transfusion. – 2006. – Vol. 46. – P. 327–338. http://doi.org/10.1111/j.1537-2995.2006.00724.x.

19. Klein A., Agarwal S., Cholley B. et al. A review of European guidelines for patient blood management with a particular emphasis on antifibrinolytic drug administration for cardiac surgery // J Clin Anesth. – 2022. – Vol. 78. – P. 110654. http://doi.org/10.1016/j.jclinane.2022.110654.

20. Lemmer J. H. Jr., Stanford W., Bonney S. L. et al. Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double-blind, placebo-controlled study // J Thorac Cardiovasc Surg. – 1994. – Vol. 107, № 2. – P. 543–551. PMID: 7508070.

21. Mahdy A. M., Webster N. R. Perioperative systemic haemostatic agents // Br J Anaesth. – 2004. – Vol. 93, № 6. – P. 842–58. http://doi.org/10.1093/bja/aeh227.

22. Makam R., Balaji A., Al Munaer M. et al. Aprotinin in high-risk isolated coronary artery bypass graft patients: a 3-year propensity matched study // J Cardiothorac Surg. – 2024. – Vol. 19, № 1. – P. 459. http://doi.org/10.1186/s13019-024-02837-1.

23. Mangano D. T., Tudor I. C., Dietzel C. Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery // N Engl J Med. – 2006. – Vol. 354, № 4. – P. 353–365. http://doi.org/10.1056/NEJMoa051379.

24. Pagano D., Howell N. J., Freemantle N. et al. Bleeding in cardiac surgery: the use of aprotinin does not affect survival // J Thorac Cardiovasc Surg. – 2008. – Vol. 135, № 3. – P. 495–502. http://doi.org/10.1016/j.jtcvs.2007.11.045.

25. Ranucci M., Castelvecchio S., Romitti F. et al. Living without aprotinin: The results of a 5–year blood saving program in cardiac surgery // Acta Anaesthesiologica Scandinavica. – 2009. – Vol. 53, № 5. – P. 5730580. http://doi.org/10.1111/j.1399-6576.2008.01899.x.

26. Reidy B., Aston D., Sitaranjan D. et al. Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair // Transfusion. – 2024. – Vol. 64, № 5. – P. 846–853. http://doi.org/10.1111/trf.17819.

27. Royston D. Intraoperative coronary thrombosis: can aprotinin be incriminated? // J Cardiothorac Vasc Anesth. – 1994. – Vol. 8, № 2. – P. 137–141. http://doi.org/10.1016/1053-0770(94)90050-7.

28. Salenger R., Mazzeffi M. A. The 7 Pillars of blood conservation in cardiac surgery // Innovations. – 2021. – Vol. 16, № 6. – P. 504–509. http://doi.org/10.1177/15569845211051683.

29. Samama C. M., Langeron O., Rosencher N. et al. Aprotinin versus placebo in major orthopedic surgery: a randomized, double-blinded, dose-ranging study // Anesth Analg. – 2002. – Vol. 95, № 2. – P. 287–293. http://doi.org/10.1097/00000539-200208000-00005.

30. Schulze K., Graeter T., Schaps D. et al. Severe anaphylactic shock due to repeated application of aprotinin in patients following intrathoracic aortic replacement // Eur J Cardiothorac Surg. – 1993. – Vol. 7, № 9. – P. 495–496. http://doi.org/10.1016/1010-7940(93)90280-o.

31. Shaw A. D., Stafford-Smith M., White W. D. et al. The effect of aprotinin on outcome after coronary-artery bypass grafting // N Engl J Med. – 2008. – Vol. 358, № 8. – P. 784–793. http://doi.org/10.1056/NEJMoa0707768.

32. Squiccimarro E., Stasi A., Lorusso R. et al. Narrative review of the systemic inflammatory reaction to cardiac surgery and cardiopulmonary bypass // Artif Organs. – 2022. – Vol. 46, № 4. – P. 568–577. http://doi.org/10.1111/aor.14171.

33. Tibi P., McClure R. S., Huang J. et al. STS/SCA/AmSECT/SABM Update to the Clinical Practice Guidelines on Patient Blood Management // J Extra Corpor Technol. – 2021. – Vol. 53, № 2. – P. 97–124. http://doi.org/10.1182/ject-2100053.

34. Walkden G. J., Verheyden V., Goudie R. et al. Increased perioperative mortality following aprotinin withdrawal: A real-world analysis of blood management strategies in adult cardiac surgery // Intensive Care Med. – 2013. – Vol. 39. – P. 1808–1817. http://doi.org/10.1007/s00134-013-3020-y.

35. Wendel H. P., Heller W., Michel J. et al. Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage // J Thorac Cardiovasc Surg. – 1995. – Vol. 109, № 6. – P. 1164–72. http://doi.org/10.1016/S0022-5223(95)70200-8.

36. Zimmermann E., Zhu R., Ogami T. et al. Intraoperative autologous blood donation leads to fewer transfusions in cardiac surgery // Ann Thorac Surg. – 2019. – Vol. 108, № 6. – P. 1738–1744. http://doi.org/10.1016/j.athoracsur.2019.06.091.