BACKGROUND:Aprotinin significantly decreases postoperative blood loss, yet its exact mechanism of action remains unproven. METHODS:To study the cytoprotective effect on platelets, we collected blood samples from patients during cardiopulmonary bypass (CPB) operations performed with or without aprotinin. Analysis included whole-blood flow cytometry. RESULTS:The highest percentages of activated platelets (positive for GMP-140 expression) were bound to leukocytes and erythrocytes in all CPB patients. Platelet-platelet activation did not reveal any marked differences between groups. However, in the platelet-cell bound region, increased ristocetin-stimulated platelet activation was observed from 30 minutes on CPB to 90 minutes after CPB with aprotinin (11.9% +/- 5.1% to 33.1% +/- 8.6%; p < 0.05), but not without aprotinin (17.5% +/- 0.1% to 17.9% +/- 2.3%). Platelet autoactivation increased more in the untreated group with time on CPB. CONCLUSIONS:This study demonstrates that in the presence of aprotinin, platelets remain unstimulated during CPB and the von Willebrand GPIb-mediated activatability of platelets is preserved, thus maintaining a viable platelet population. Most important, this study reveals that these mechanisms are more related to platelet-leukocyte than to platelet-platelet interactions.