Inhibition of Platelet Aggregation by Supernates from Stored Red Blood Cells
ARMY INST OF SURGICAL RESEARCH SAN ANTONIO TX
Pagination or Media Count:
Uncontrolled hemorrhage is the second leading cause of death to war fighters on the battlefield next to central nervous system injury. Hemorrhagic deaths are potentially preventable if bleeding can be controlled early, but hemorrhage control is complicated by trauma-induced coagulopathy characterized by loss of platelets and coagulation factors, dysfunctional platelets, and increased fibrinolysis. The specific dysfunction of platelets remains to be elucidated, but may be of greater importance than platelet number for clot integrity. In a previous study of the proinflammatory effects of supernates from stored RBC, we observed that platelets in blood incubated with supernates from stored RBC exhibited lower anti-CD41a-FITC fluorescence, which indicated decreased expression of GPIIbIIIa on the platelet membrane. Because activated GPIIbIIIa binds fibrinogen and facilitates formation of platelet aggregates that are necessary to form stable platelet plugs during hemostasis, we designed this study to determine if supernates from RBC impaired platelet aggregation as a consequence of reduction in GPIIbIIIa expression. Blood was collected from healthy volunteers, prepared into non-leukoreduced NLR and leukoreduced LR packed RBC with AS-5 and stored at 1-6 deg C for six weeks. Supernates obtained from samples collected from RBC units every two weeks were mixed with freshly collected ABO-compatible blood. Platelets in each incubated blood sample were evaluated for GPIIbIIIa expression by flow cytometry and for aggregation response to collagen by whole blood aggregometry. We observed that supernates from stored RBC decreased GPIIbIIIa expression and inhibited platelet aggregation proportionately. Furthermore, both activities increased as a function of storage age, which was indicative of accumulation of the bioactive substances. Supernates from LR RBC, however, did not alter either GPIIbIIIa or aggregation.
- Medicine and Medical Research