The platelet thrombin receptor and postoperative bleeding.
BACKGROUND
We hypothesized that small amounts of thrombin desensitize the platelet thrombin receptor during cardiopulmonary bypass (CPB), resulting in postoperative platelet dysfunction and bleeding.


METHODS
Seventy-nine patients were entered into a study designed to measure changes in platelet thrombin receptor function during CPB and to correlate them to postoperative bleeding. In addition to measurements of clinical blood loss, platelet function tests of aggregation, activation, and 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 interactions during CPB.


RESULTS
Compared with preoperative values, both aggregometry and flow cytometry measured a significant reduction of TRAP-induced activation immediately and up to 24 hours after CPB. The response of other activating agents returned to normal by 24 hours. Postoperatively, 8 of 79 patients required excessive blood transfusion (> or = 10 units of blood products) and had significantly decreased TRAP-induced aggregation response.


CONCLUSIONS
Our results show that (1) platelet activation, aggregation, and adhesion to leukocytes induced by TRAP are reduced after CPB, (2) decreased thrombin receptor responsiveness is associated with excessive postoperative blood loss, and (3) because the aggregation and activation responses are different for TRAP and thrombin, there may be a second thrombin receptor on platelets that is protected from damage during CPB. These results imply that prevention of the CPB-induced effects on the thrombin receptor will lessen postoperative morbidity associated with blood transfusion.
Ferraris
V A
VA
Division of Cardiothoracic Surgery, Albany Medical College, New York, USA.
Ferraris
S P
SP
Singh
A
A
Fuhr
W
W
Koppel
D
D
McKenna
D
D
Rodriguez
E
E
Reich
H
H
D016063:Blood Loss, Surgical; D001792:Blood Platelets / Q000378:metabolism*; D001803:Blood Transfusion; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D005434:Flow Cytometry; D006801:Humans; D039661:Integrin beta3; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000494:pharmacology; D019106:Postoperative Hemorrhage / Q000097:blood* / Q000628:therapy; D018179:Receptors, Thrombin / Q000378:metabolism*
D039661:Integrin beta3; D019007:P-Selectin; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D018179:Receptors, Thrombin; C073659:glycoprotein IIIa-derived peptide (217-231); C072032:thrombin receptor peptide (42-55)