Objective: To determine whether two low-dose regimens of aprotinin influence platelet function.
Design: Prospective, randomized, single-blinded trial.
Setting: University teaching hospital performing 600 cardiac operations per year.
Participants: Fifty-nine patients scheduled for cardiac surgery undergoing cardiopulmonary bypass (CPB) of expected duration of 60 minutes or more.
Interventions: Patients were randomized into three groups. Group C (control) included 21 patients who did not receive aprotinin. In group A2, 17 patients received 14,286 kallikrein inhibitor units (KIU)/kg (2 mg/kg) of aprotinin before surgery, followed by a continuous infusion of 7,143 KIU/kg/h (1 mg/kg/h) until the end of surgery. In group A4, 19 patients received 28,572 KIU/kg (4 mg/kg) of aprotinin before surgery, followed by the same infusion.
Measurements and main results: Postoperative bleeding and transfusion requirements were significantly less in group A4. Changes in platelet number and function were similar in the three groups. Platelet aggregation was assessed in four periods: before CPB (T1), post-CPB (T2), and 2 hours (T3) and 4 hours (T4) after CPB. Platelet aggregation induced by adenosine diphosphate, 1 and 2 micromol/L; ristocetin, 1 mg/mL; and arachadonic acid (AA), 1.4 mmol/L, decreased at T2 (p < 0.001) in all groups, and for the ristocetin and AA groups, remained at less than baseline values at T3 and T4. In five patients from each group, platelet receptors for glycoprotein IIb-IIIa (GPIIb-IIIa) and expression of platelet activation markers, guanosine monophosphate 140 (GMP-140) and lysosomal protein, were measured by flow cytometry before and after CPB. Modifications in the expression of GPIIb-IIIa were always modest and without statistical significance. Platelet activation markers, GMP-140 or lysosomal protein, nearly doubled from baseline to post-CPB only in the A4 group, whereas they remained stable in both other groups (statistically not significant).
Conclusion: The two regimens of aprotinin, both considered low dosage, did not exert a protective effect on platelet function. Neither dose produced changes in platelet GPIIb-IIIa or platelet activation markers. However, bleeding and transfusion needs were decreased.