Aprotinin, cardiac surgery, and factor V Leiden

Area of Science:

• Cardiovascular Surgery
• Hematology
• Pharmacology

Background:

• Aprotinin reduces blood transfusions in cardiac surgery.
• Aprotinin inhibits activated protein C (APC), a key regulator of coagulation.
• Factor V (FV) Leiden is an inherited condition causing APC resistance.

Purpose of the Study:

• To investigate the effect of aprotinin on blood transfusion requirements in cardiac surgery patients with and without FV Leiden.
• To explore the interaction between aprotinin and APC in patients with FV Leiden.

Main Methods:

• Cardiac surgery patients were screened for FV Leiden using clot-based assays and PCR.
• Blood transfusion amounts were recorded.
• In vitro studies assessed aprotinin's effect on APC inhibition in normal and FV Leiden plasma.

Main Results:

• 13% of 162 patients had FV Leiden and required fewer transfusions than matched controls.
• Aprotinin induced an FV Leiden-like defect in normal plasma and worsened the defect in FV Leiden plasma.
• Aprotinin competitively inhibited APC in a dose-dependent manner.

Conclusions:

• Aprotinin's inhibition of APC may contribute to its hemostatic effects.
• Aprotinin use in FV Leiden patients could severely impair protein C pathway function, potentially leading to thrombosis.