Platelet preserving effects of Aprotinin

This project will study the mode of action of aprotinin, a commonly used drug to prevent or treat bleeding complications in cardiac surgery. Aprotinin has a long clinincal history, but was suspended from clinical use between 2007 and 2012. However, in 2012 this suspension was lifted by the European Medicines Agency, and Nordic Pharma reintroduced aprotinin, specifically for use during complex cardiac surgery.

Despite decades of clinical use, little is known on the mode of action of this drug. Nordic Pharma and the UMCG think that a better understanding of how exactly the drug contributes to reduction of blood loss will lead to a more rational and more effective approach to its use. As cardiac surgery is frequently accompanied by substantial blood loss, and as it has been well established that blood transfusions in these patients are associated with an increased risk for complications and poor outcome, every clinical intervention that can reduce blood loss is of direct benefit for the patient, and will reduce healthcare costs due to the reduction of complications.

They will study the mode of action of aprotinin in a laboratory setting, and also study the hypothesis that aprotinin next to inhibitory effects on the system that breaks down blood clots, also has beneficial effects on blood platelets. The effects is hypothesised to be absent in tranexamic acid, a competitor drug that will also be studied.

The project will provide in-depth mechanistic detail in the mode of action of aprotinin in the setting of cardiac surgery. Importantly, the experiments will take concomitant antiplatelet therapy and the profound lytic environment of blood which is present in patients on a heart-lung machine into account. They will thus provide detail of the mode of action of aprotinin in situations mimicking the blood compartment of patients undergoing cardiac surgery.