Cardiovascular Devices and Platelet Interactions: Understanding the Role of Injury, Flow, and Cellular Responses

The objectives of the 2011 Platelet Colloquium were to gain a better understanding of the role of platelets and inflammatory cells in the response to cardiovascular device–associated injury; to describe the relationship between cardiac devices, shear stress, and alterations in platelet biology and function; and to review evidence derived from in vitro, in vivo, and clinical investigations supporting therapies to modify platelet and inflammatory cell–associated responses to device-related injury. Accordingly, this review summarizes the evidence for translating basic scientific concepts underlying circulatory and device-associated vascular injury to the clinical development and use of cardiac devices, supplemented by findings from the literature. Insights for platelet receptor activation, inflammatory cell biology, endothelial dysregulation, and the effects of biomechanical stress on coagulation and hemostatic proteins were examined to better determine the pathobiology, incidence, and possible prevention of adverse events in patients receiving cardiac devices. ### Shear Stress and Platelet Activation Hemodynamics play a key role in thrombus formation. Pathophysiological shear stress induces activation of platelets and the endothelium, increases platelet–leukocyte interactions, and promotes thrombin generation. The initial tethering of rolling activated platelets, subsequent stable adhesion, and aggregation each are influenced by shear stress on the vessel wall, which can range from 11.4 to 30.4 dyne/cm2 in large arteries and up to 380 dyne/cm2 at critical areas of arterial stenosis.1 Along a diseased vessel, shear forces will vary dramatically within short distances, increasing as the lumen narrows and then decreasing in the poststenotic vascular segment.2 Several platelet membrane proteins serve as mechanosensors, most notably glycoprotein (GP) Ib and its ligand, von Willebrand factor (vWF).3 vWF circulates as highly adhesive multimers (ultralarge vWF) that are cleaved by a disintegrin and metalloproteinase with thrombospondin type 1 motif member 13 (ADAMTS-13). Depletion or accumulation of ultralarge vWF, as a consequence of inappropriate ADAMTS-13 proteolysis, results in pathological bleeding …