Microparticles and left ventricular assist device complications: a causal association?

Although left ventricular assist device (LVAD) use continues to rise, recent publications reporting increasing rates of pump thrombosis ground us in the reality of deviceassociated complications. As we scramble to explain the clinical and rheological reasons for these trends, published efforts thus far have focused on identifying clinical predictors of LVAD complications. Pump thrombosis has been associated with conditions resulting in lower LVAD flow (lower speed operation and high systemic blood pressure), echocardiographic indicators of inadequate decompression (abnormal response to speed ramping, increased LV diameter, and frequent aortic valve opening), cannula malposition, rising lactate dehydrogenase (LDH) levels, infections, and lapses in anti-coagulation. Mechanistic explanations, however, are lagging behind. In the present study, Nascimbene et al analyzed the circulating concentrations of membrane microparticles (MPs), a biomarker with the mechanistic potential to predict complications in the “pre-disease” state for vascular, inflammatory, and pro-thrombotic conditions. MPs are membrane-derived vesicles released from a wide variety of cell types, including erythrocytes, endothelial cells, platelets, vascular smooth muscle cells, and cardiomyocytes. The vesicles form by outward blebbing of the outer membrane when the cells are stressed or activated by inflammation, shear forces, or various signaling pathways (i.e., mediators of the coagulation cascade). During MP formation, phosphatidylserine (PS), an aminophospholipid typically found on the inner leaflet of the plasma membrane of healthy cells, becomes externalized. Although MPs were initially thought to be biologically inert “cellular debris,” they are now known have regulatory and signaling roles for increasing inflammation, oxidative stress, and angiogenesis. In addition, the negatively charged PS particles covering the surfaces of these molecules have a pro-coagulant effect through interactions with positively charges clotting factors. MPs derived from platelets are in fact exponentially more pro-coagulant than activated