Fig. 1.

Proposed additional mechanisms of hypershear-mediated platelet activation. A.) With increasing shear dose = intensity × time, platelets undergo shape change, pseudopod extension, progressive additive damage with membrane rents and pore formation, fragmentation, membrane eversion, and ultimately microparticle generation. B.) Three mechanistic pathways are outlined: a mechanodestructive pathway in which repetitive shear damage accumulates, platelets being incapable of repair, eventually sustain irreversible damage – as illustrated in A above; a mechanoactivation pathway wherein shear-sensitive channels, pore and gates may open; and a mechanotransductive pathway in which the whole cell (based on stiffness), the cell membrane (based on fluidity), and mechanic-biochemical linkage pathways capture and convert shear to internal activating signals.