EVIDENCE FOR SELECTIVE DEGRADATION OF PLATELET GP IIB IIIA COMPLEX AFTER PROLONGED IN-VITRO VENTRICULAR ASSIST/

Background: Left ventricular assist devices (VAD) have improved surviv al in patients with end-stage heart failure. Past studies have shown t hat interactions between blood and synthetic surfaces promote initial bleeding and later thromboembolism. The exact mechanism of blood activ ation during VAD circulation remains unclear, The purpose of this stud y was to test the hypothesis that platelet glycoprotein (GP) IIb/IIIa receptor degradation occurs during clinical use of ventricular assist devices. Methods: Five in vitro nonpulsatile centrifugal VAD circuits were simulated for 4 days using 450 mt of fresh human whole blood. Tem perature, activated clotting time, pH, pCO(2), pO(2), Ca++, and glucos e were maintained at physiologic values. Flow was maintained at a cons tant 2.0 L/min/m(2), We examined whole blood platelet aggregation indu ced by ristocetin, collagen, and adenosine diphosphate (ATP), We also examined whole blood platelet degranulation induced by collagen and AD P, Results: Platelet aggregation in response to ristocetin, collagen, and ADP irreversibly and progressively declined with prolonged circula tion in the VAD, While ADP-induced aggregation declined within the fir st hour, ristocetin and collagen-induced aggregation declined after 10 hours. Collagen-induced platelet degranulation decreased similar to a ggregation, whereas ADP-induced degranulation continued and was preser ved throughout the experiment. Conclusions: These results suggest prol onged circulation of human blood in a VAD circuit irreversibly impair platelet aggregation. The response of circulating platelets to individ ual agonists suggests that this platelet degradation is partially rece ptor specific. In our VAD system, ADP-stimulated platelet aggregation is more rapidly degraded with circulation. These results offer prelimi nary evidence that circulation of human blood in a VAD circuit leads t o early degradation of the platelet GP IIb/IIIa complex. GP IIb/IIIa c omplex degradation is likely to be the mechanism of early VAD associat ed bleeding.