Platelet storage by refrigeration. (A) Desialylation-mediated clearance. Sialic acid is removed by Neu1 from platelet glycoproteins following refrigeration. The exposed β-gal is recognized by the AMR, and the platelets are cleared by hepatocytes. The utility of neuraminidase inhibitors such as DANA or the AMR inhibitor asialofetuin can impede the clearance of desialylated platelets. (B) GPIbα clustering–mediated clearance. GPIbα clusters on platelet surface, and14-3-3ζ dissociates from Bad and associates with GPIbα after refrigeration. This induces the platelet apoptosis process. A broad caspase inhibitor Q-VD-Oph or arachidonic acid depletion can inhibit the apoptosis process of refrigerated platelets and improve the posttransfusion recovery and survival. (C) VWF binding–mediated clearance. Refrigeration leads to binding of plasma VWF to GPIbα. Upon transfusion and thus exposure to the shear flow, VWF binding may generate a pulling force and induces MSD unfolding, leading to rapid platelet clearance. OGE cleaves off the LBD of GPIbα, therefore precludes the VWF-GPIbα interaction and subsequently platelet clearance.