Tirofiban administration attenuates platelet and platelet-neutrophil conjugation but not neutrophil degranulation during in vitro VAD circulation

Ventricular Assist Devices (VADs) have been used as bridges to heart transp lantation. However, VAD circulation is complicated by the incidence of thro mboembolism, prolonged bleeding, and activation of the inflammatory cascade . We hypothesize that platelet and neutrophil activation are interrelated a nd linked to the activation of the glycoprotein (GP) Ilb/llla platelet rece ptor. The purpose of this study is to evaluate the effects of Tirofiban, a platelet CP Ilb/llla receptor inhibitor, on platelet and neutrophil activat ion during simulated VAD circulation. Two groups of five in vitro VAD circu its were simulated with and without Tirofiban using 450 cc of human blood. Blood samples were drawn at specific time intervals up to 72 hours, measuri ng leukotriene C4 (LTC4), platelet factor four (PF4), and neutrophil elasta se. Tirofiban decreased serum levels of PF4 and LTC4 during VAD circulation . Neutrophil elastase secretion was not affected by Tirofiban administratio n. Preconditioning of VAD circulation with Tirofiban attenuated platelet ac tivation as demonstrated by a decrease in serum PF4 levels. Tirofiban admin istration ameliorates the inflammatory response by altering plateiet-neutro phil interaction as demonstrated by a decrease in LTC4 production. Continue d elastase secretion indicates that the inflammatory response is not comple tely inhibited by Tirofiban administration. These results suggest that neut rophils may be activated by alternative mechanisms. Early complement activa tion has been demonstrated during in vivo and in vitro VAD circulation and may play a role in mediating inflammatory and thromboembolic reactions duri ng VAD use.