Effects of aprotinin on anticoagulant monitoring: Implications in cardiovascular surgery

Abstract

This study was designed to evaluate anticoagulant monitoring of heparin and platelet function in the presence of aprotinin. Aprotinin added to heparinized whole blood at concentrations equal to (30 μg/mL), twice, and four times that used in cardiopulmonary bypass operations synergistically elevated the activated clotting time (ACT) (536 ± 73, 651 ± 86, and 787 ± 71 seconds, respectively) over the value with heparin alone (384 ± 66 seconds) (p < 0.001). In addition, the ACT of heparin-aprotinin mixtures supplemented with protamine showed that the heparin was not completely neutralized (131 ± 12 versus 98 ± 7 seconds). Specific tests revealed that the effect on ACT caused by aprotinin is not equal to the anticoagulant effect of heparin. Thus there is a risk of underheparinization if the ACT is used as a monitor when aprotinin is present. Furthermore, protamine doses relative to the heparin concentration, and not relative to the ACT, should be used to reverse heparin. In studying the effects of aprotinin on platelet function, there was a significant inhibition of aggregation when normal platelets were supplemented with aprotinin, but not for platelets of postoperative patients. This suggests that aprotinin may interact more favorably with nonactivated platelet surfaces, reducing or inhibiting the expression of receptors. Thus it is necessary to treat a patient with aprotinin before beginning cardiopulmonary bypass. Based on these data, the effect of aprotinin on the hemostatic system and its drug interactions must be considered to optimize safety and efficacy during cardiopulmonary bypass operations.