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 (<4h) clusters glycoprotein (GP) Ibalpha receptors, and beta(2) integrins on hepatic macrophages recognize clustered beta GlcNAc 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.

Figure 1. Schematic diagram of the human von Willebrand factor receptor subunit GPIbα

A typical, complete N-glycan identified on GIPbα is shown (inserted box).

Figure 2. Lectin receptors mediating the clearance of cooled platelets

The von Willebrand factor receptor (vWfR) complex, specifically GPIbα, has complete and incomplete N-linked glycans with exposed βGlcNAc and/or galactose residues. Clustering of vWfRs and of exposed β-GlcNAc initiates recognition and phagocytosis by the macrophage αMβ2 integrin following short-term refrigeration. Extended refrigeration is followed by additional surface changes such as “hyperclustering” of receptors and galactose exposure and some vWf binding. These changes induce clearance by asialoglycoprotein receptors on hepatocytes (Ashwell-Morell receptors) and macrophages (α_mβ₂).