Exposure of human platelets to uniform shear stress ex vivo rapidly induces shedding of GPIbα and GPVI, while patients with cardiovascular disease, heart failure, and/or circulatory support devices (with acutely elevated fluid shear stress within these devices) show decreased platelet surface GPIbα/GPVI [1,20,21,22] and elevated shed soluble GPVI (sGPVI) in plasma, consistent with increased shedding [22,23]. Here, GP6 is linked to heart failure.