The advent of continuous flow (CF) pumps for patients with severe heart failure has led to
marked improvements in survival; however, pump operation remains fraught with adverse
thrombotic events. This climbing rate of thrombosis and stroke during CF pump support has led
to a recent warning by the US Food and Drug Administration. Despite a rising incidence of
pump thrombosis and its downstream complications of stroke, the hematologic mechanisms behind
these devastating adverse events remain uncertain. Recently, it has been recognized that CF
pump induced hemolysis precedes and is associated with thrombosis. In-vitro studies show
increased platelet function with exposure to products of hemolysis, which is also known to
occur in diseases of intravascular hemolysis such as sickle cell anemia. This proposal will
investigate if hemolysis associated increased platelet function can be reduced by a
potentiation of nitric oxide signaling by an oral phosphodiesterase-5 inhibitor, sildenafil.
Elucidating mechanisms of hemolysis induced thrombosis may inform best strategies for
prevention of end organ damage and maintaining optimal CF pump operation.