About aprotinin

Aprotinin can reduce blood loss and the need for transfusion in appropriate patients undergoing isolated CABG1,2

Aprotinin is a serine protease inhibitor that has effects on coagulation, fibrinolysis, and platelet function.1,2

These mechanisms of action help mitigate tissue reperfusion injury and changes in the patient’s coagulation cascade and systemic inflammatory response, post isolated CABG.2

Aprotinin has a greater range of interactions in the coagulation and tissue factor pathways than tranexamic acid.2

To find out more about the different parts of the pathway, hover your cursor over the information icons  in the diagram below


Inhibition of kallikrein reduces activation of intrinsic pathway

Inhibition of tissue factor reduces the activation of the extrinsic pathway

Thrombin activity reduced

Reduction of thrombin activation of PAR-1 reduces activation of platelets

Inhibition of TPA activator reduces the formation of plasmin

Direct inhibition of plasmin reduces widespread fibrinolysis

Results in reduced activation of the inflammatory response and decreases pulmonary and cardiac oxidative stress

Aprotinin inhibits both the contact activation and tissue factor pathways helping to reduce the risk of bleeding.2

Understanding aprotinin safety3-8

Aprotinin was first licensed for use in reducing blood loss in 1987.3 In 2007, the company responsible for marketing aprotinin suspended the licence following the release of some preliminary data suggesting an increased mortality in aprotinin treated patients in the Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) trial, published in May 2008.3-5 The results from this study have since been questioned due to several methodological deficiencies.

The licence suspension for aprotinin was lifted in 2013, supported by additional data and new analyses.4,6

Renal impairment: Renal dysfunction could be triggered by aprotinin, particularly in patients with pre-existing renal dysfunction. Careful consideration of the balance of the risks and benefits is therefore advised before administration of aprotinin to patients with pre-existing impaired renal function or those with risk factors (such as concomitant treatment with aminoglycosides).1

Aprotinin use does not independently increase the risk of renal failure in patients undergoing cardiac surgery.10 A transient rise in creatinine observed in some patients receiving aprotinin has been shown to normalise at post-operative day 3.10

A transient rise in creatinine observed in patients receiving aprotinin resolves to normal levels by post-operative day 3, at which point there was no difference between treatment arms.10

References

    1. Aprotinin 10,000 KIU/ml Injection BP Summary of Product Characteristics. Available from: https://www.medicines.org.uk/emc/product/2472/smpc. Accessed December 2020.
    2. McEvoy MD et al. Aprotinin in Cardiac Surgery: A Review of Conventional and Novel Mechanisms of Action. Anesth Analg. 2007;105:949–62.
    3. European Society of Anaesthesiology task force reports on place of aprotinin in clinical anaesthesia. Aprotinin: Is It Time to Reconsider? Eur J Anaesthesiol. 2015;32:591–5.
    4. European Medicines Agency. Assessment report. Antifibrinolytics containing aprotinin, aminocaproic acid and tranexamic acid. 18 September 2013. Available from: https://www.ema.europa.eu/en/documents/referral/assessment-report-antifibrinolytic-medicines-aprotinin_en.pdf. Accessed July 2020.
    5. Fergusson DA et al. A Comparison of Aprotinin and Lysine Analogues in High-Risk Cardiac
      Surgery. N Engl J Med. 2008;358:2319–2331.
    6. Howell N et al. J Thorac Cardiovasc Surg. 2013;145:234–40.
    7. Henry DA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2011;(1):CD001886.
    8. Health Canada. Final report—expert advisory panel on Trasylol (aprotinin) 2011: Available from: https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2011/13544a-eng.php
    9. Boer C et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. J Cardiothor Vasc Anesth. 2018;32:88–120.
    10. Deloge E et al. Aprotinin vs. tranexamic acid in isolated coronary artery bypass surgery. Eur J Anaesthesiol 2017;34:1–8.