BACKGROUND Thrombocytopenia and impaired platelet function after cardiopulmonary bypass (CPB) contribute to postoperative bleeding and may increase blood transfusion requirements. We tested the hypothesis that reversible inhibition of glycoprotein IIb/IIIa integrin-mediated platelet adhesion would reduce postoperative bleeding after CPB. RESULTS Twelve mongrel dogs (21 to 24 kg) underwent 2.5 hours of hypothermic CPB followed by 6 hours of observation. The study group (n = 6) received a 90-micrograms/kg IV bolus of the glycoprotein IIb/IIIa inhibitor Integrelin, followed by continuous infusion (2 micrograms/kg per minute) during CPB; the control group (n = 6) received only drug vehicle. Platelet number and aggregometry, PaO2, and chest tube output were assessed serially. Lung wet weight, histology, and myeloperoxidase activity were also measured. At 120 minutes after CPB, the control group had significantly lower platelet counts (expressed as percent of pre-CPB values) when compared with the Integrelin group (control, 35.2 +/- 4.6%; Integrelin, 68.2 +/- 4.9%; mean +/- SEM; P < .05). Three hundred sixty minutes after CPB, platelet function (expressed as percent of pre-CPB aggregation induced by 10 mumol/L ADP) was better preserved in the Integrelin group (Integrelin, 20.8 +/- 3.0%; control, 43.9 +/- 10.4%; P < .05). The Integrelin group also had less total postoperative blood loss (control, 447 +/- 97 mL; Integrelin, 248 +/- 30 mL; P < .05). PaO2, lung wet weight, histology, and myeloperoxidase activity did not differ significantly between groups. CONCLUSIONS This study demonstrates that inhibition of platelet adhesion during CPB results in (1) less platelet consumption, (2) better preservation of platelet function, and (3) less postoperative bleeding. Reversible platelet inhibition may have clinical utility in minimizing postoperative bleeding and reducing blood transfusions.