Hemolysis and Platelet Activation during Continuous Flow Mechanical Circulatory Support

The advent of continuous flow mechanical circulatory support (CF MCS) devices for patients with severe heart failure has led to marked improvements in survival; however, pump operation remains fraught with adverse thrombotic events such as stroke. Despite alterations in device design, the rate of disabling stroke remains elevated and the hematologic mechanisms behind these devastating adverse events remain unknown. This proposal will investigate if during CF MCS hemolysis creates a pro-thrombotic state through increasing platelet activation and if pharmacologic potentiation of nitric oxide signaling by an oral phosphodiesterase-5 inhibitor sildenafil lowers platelet activity. Elucidating mechanisms of hemolysis induced thrombosis may inform targeted anti-thrombotic strategies for prevention of end organ damage.