Platelet-sparing properties of aprotinin

Abstract

BACKGROUND Cardiac surgery involving cardiopulmonary bypass (CPB) is associated with the risk of acquired coagulopathy, including dysregulated fibrinolysis, which can result in life-threatening bleeding complications. Aprotinin, an antifibrinolytic agent, has been recommended for the prevention of these complications. Its effectiveness has been attributed to its ability to nonspecifically inhibit various serine proteases involved in the coagulation and fibrinolysis cascade. Additionally, aprotinin may protect platelets from CPB-induced dysfunction through a platelet-sparing effect, further enhancing its efficacy. OBJECTIVES The biochemical pathways underlying aprotinin's platelet-sparing effect remain unclear. Furthermore, it is uncertain to what extent this effect contributes to reducing blood loss and need for transfusion. DESIGN A scoping review DATA SOURCES MEDLINE, Embase and Cochrane were searched from inception until 21 December 2023. ELIGIBILITY CRITERIA Studies in which a platelet-sparing effect of aprotinin was investigated. These included systematic reviews; experimental, and observational studies describing healthy humans, patients, or animals undergoing any type of surgery; studies in which donated blood was used for in-vitro studies. RESULTS Sixty-four studies were deemed eligible, the majority of which observed a platelet-sparing effect, attributing it to the inhibition of platelet aggregation (via protection of glycoprotein (GP) IIb/IIIa receptors), platelet adhesion (by protection of GP Ib receptors), both aggregation and adhesion receptors, proteolysis of protease-activated receptor 1 receptors, platelet activation (by inhibition of plasmin) and platelet activation (by inhibition of thrombin). A dose-dependency of the platelet-sparing effect was investigated in both in-vitro studies and randomised controlled trials, yielding mixed results. No studies have explored the relative contribution of aprotinin's platelet-sparing effect and its antifibrinolytic effect in reducing blood loss and need for transfusion. CONCLUSIONS This review elucidated current knowledge on how aprotinin influences platelets and exerts its platelet-sparing effect, while highlighting gaps in the existing literature.