PubMed1996
Platelet abnormalities have been blamed for the hemostatic defect that develops after cardiopulmonary bypass (CPB), but investigators have not been able to agree upon an intrinsic platelet abnormality responsible for the observed defect. To better define the blood components responsible for this post-operative hemostatic defect, we compared platelet function in whole blood (WB) to that in platelet-rich plasma (PRP) in 33 patients undergoing coronary artery bypass grafting. We measured platelet aggregation in response to various platelet agonists, including thrombin and TRAP-6 (a 6-amino acid peptide that activates the thrombin "tethered ligand" receptor site). In WB there was a lasting, diminished response to TRAP-6, but not to gamma-thrombin, after CPB. Control experiments showed that this diminished response to TRAP-6: (1) was not related to heparin or heparin-protamine complexes, (2) was not the result of hemodilution during CPB, (3) was not related to increased amounts of naturally occurring enzymes (aminopeptidases) that degrade TRAP, and (4) was not able to be reversed by the addition of as much as a 10-fold excess of the usual TRAP-6 aggregating dose to WB preparations. In contrast, no corresponding defect in platelet aggregation could be identified in PRP obtained from patients after CPB. These results show that, in post-operative blood samples, blood components present in WB and not in PRP (eg, red blood cells, activated white cells or platelets bound to white cells) diminish the ability of TRAP peptides to activate the thrombin receptor but do not decrease the ability of gamma-thrombin to induce platelet aggregation. This suggests that for circulating platelets after CPB: (1) interactions of platelets with other blood cell elements are the cause of altered postoperative platelet reactivity rather than any intrinsic CPB-induced platelet defect, (2) drugs, such as aprotinin, that limit activation of white cells and the fibrinolytic system may also have beneficial effects on platelet function after CPB, and (3) alternate mechanisms exist that allow thrombin, but not TRAP-6, to activate platelets normally after CPB (perhaps a second, as yet undefined, thrombin receptor).