Refrigeration-induced phenotypic and functional changes in platelets associated with clearance. (A) Platelets circulate at 37°C (body core temperature). (B) Exposure to RT results in low-level activation with intracellular calcium release and integrin activation. (C) Further decreasing the temperature to 1°C to 6°C leads to shape change, increase in calcium concentration, and specific clearance mechanisms via αMβ1 on liver macrophages and VWF. (D) Extended storage leads to aggregate formation, clearance by the hepatic Ashwell-Morell receptor (AMR), loss of GPVI and other glycoproteins, phosphatidylserine (PS) exposure, and α-degranulation. MP, microparticles. Figure 1 was created at BioRender.com.