THE PLATELET THROMBIN RECEPTOR AND POSTOPERATIVE BLEEDING

Background. We hypothesized that small amounts of thrombin desensitize the platelet thrombin receptor during cardiopulmonary bypass (CPB), r esulting in postoperative platelet dysfunction and bleeding. Methods. Seventy-nine patients were entered into a study designed to measure ch anges in platelet thrombin receptor function during CPB and to correla te them to postoperative bleeding. in addition to measurements of clin ical blood loss, platelet function tests of aggregation, activation, a nd cell-cell adhesion were used. The thrombin receptor agonist peptide (TRAP) was used to activate the platelets. Flow cytometry was used to measure various platelet surface markers and platelet-white cell inte ractions during CPB. Results. Compared with preoperative values, both aggregometry and flow cytometry measured a significant reduction of TR AP-induced activation immediately and up to 24 hours after CPB. The re sponse of other activating agents returned to normal by 24 hours. Post operatively, 8 of 79 patients required excessive blood transfusion (gr eater than or equal to 10 units of blood products) and had significant ly decreased TRAP-induced aggregation response. Conclusions. Our resul ts show that (1) platelet activation, aggregation, and adhesion to leu kocytes induced by TRAP are reduced after CPB, (2) decreased thrombin receptor responsiveness is associated with excessive postoperative blo od loss, and (3) because the aggregation and activation responses are different for TRAP and thrombin, there may be a second thrombin recept or on platelets that is protected from damage during CPB. These result s imply that prevention of the CPB-induced effects on the thrombin rec eptor will lessen postoperative morbidity associated with blood transf usion.