Novel and unexpected clearance mechanisms for cold platelets

Abstract

Storage at room temperature is limited to 5 days because of the risk of bacterial growth and loss of platelet functionality. Platelet refrigeration remains impossible, because once chilled, platelets are rapidly removed from circulation. Chilling platelets (<4 h) clusters glycoprotein (GP) Ibα receptors, and β2 integrins on hepatic macrophages recognize clustered βGlcNAc residues leading to rapid clearance of acutely chilled platelets. Prolonged refrigeration increases the exposure of galactose residues such that, unexpectedly, hepatocytes remove platelets using their asialoglycoprotein receptors. Here we review current knowledge of the mechanisms of platelet removal, the existing knowledge of refrigerated platelet function, and methods to preserve platelet concentrates long-term for transfusion.

Preanalysis Storage Conditions Influence the Measurement of Brain-Derived Neurotrophic Factor Levels in Peripheral Blood

“…Murphy and Gardner [17] reported that the immediate circulatory recovery and survival half-life of radioactive platelets after 18 h of room-temperature storage were similar to those of fresh platelets (at 55% and 4.0 days, respectively), whereas the recovery decreased to 40% with a survival half-life of only 1.3 days after 18 h of storage at 4°C. Platelet chilling induces rapid irreversible disk-to-sphere shape changes [18]. In the current study, the BDNF levels in the samples increased over a period of 6 h even when the plasma was stored at room temperature.…”

“…Platelets are metabolically active during storage at room temperature, which contributes to continuously diminished platelet function. Furthermore, metabolic products (e.g., lactate) accumulate during room-temperature storage and lead to an increase in acidity, and pH levels below 6.0-6.2 have been associated with severely diminished platelet viability [18]. …”

Regulating billions of blood platelets: glycans and beyond

“…54,55 Recently, loss of sialic acid has been identified as a determinant for the removal of senescent circulating platelets. 56 Sialic acid loss is likely mediated by upregulation of platelet sialidases, ie, Neu1 and Neu3, expressed in granular compartments and on the plasma membrane, respectively.…”

Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice

“…We also demonstrated that isolated fresh platelets have receptors bearing terminal ␤-galactose, supporting the notion that sialic acid is removed from the platelet surface during circulation. 30 Preferential cleavage of desialylated platelet VWFR, therefore, might preserve some hemostatic function in the platelets. Rapid removal, in this case, would also place a higher burden on the replenishment system.…”