APROTININ, CARDIAC-SURGERY, AND FACTOR-V-LEIDEN

BACKGROUND: Aprotinin has been shown to reduce blood transfusion in ca rdiac surgery. Aprotinin inhibits activated protein C (APC). Patients with factor V (FV) Leiden have an inherited resistance to APC proteoly sis. If the inhibition of APC by aprotinin contributes to its benefici al effect in cardiac surgery, then patients with FV Leiden undergoing cardiac surgery might be expected to require less transfusion than pat ients without FV Leiden. However, the use of aprotinin in such patient s also could compromise the protein C regulatory pathway and precipita te a clinical thrombotic event. STUDY DESIGN AND METHODS: Patients und ergoing cardiac surgery were studied for the presence of the FV Leiden defect by the use of a Russell's viper venom clot-based assay and pol ymerase chain reaction. The total amount of blood transfused was recor ded for each patient. The effect of aprotinin on the plasma of normal and FV Leiden patients was studied. Further studies were performed on the direct inhibition of APC by aprotinin. RESULTS: Over an 18-month p eriod, 162 patients were studied, of whom 13 (8%; 95% CI, 4.3-13.3%) w ere positive for FV Leiden. These 13 had a smaller requirement for blo od transfusion than the to 13 matched controls. In vitro, aprotinin in duced a FV Leiden defect in normal plasma and exacerbated the defect i n the plasma of FV Leiden patients. Aprotinin inhibited APC in a dose- dependent manner, and kinetic analysis showed competitive inhibition w ith an inhibition constant of 4.5 mu M (250 Kallikrein inhibitor units /mL). CONCLUSION: The inhibition of APC by aprotinin may contribute to its hemostatic effect. The use of aprotinin in patients with FV Leide n could cause extreme dysfunction of the protein C regulatory pathway, which could result in clinical thrombosis.