Uncommon cold: could 4°C storage improve platelet function?

Abstract

ABBREVIATIONS: b-GlcNAc = b-N-acetylglucosamine; HSR = hypotonic shock response. n 1969, Murphy and Gardner 1 demonstrated that transfused human platelets (PLTs) that have been stored at 4∞C are rapidly cleared from the circulation. They and others proved that PLTs stored at room temperature (22∞C) show significantly better recovery and survival, with a typical life span of 7 to 9 days versus only 2 to 4 days for refrigerated PLTs. 1-4 This odd phenomenon of chilled PLT clearance has had profound consequences for blood banking. For decades, all PLT products have been stored at room temperature, and because of the attendant risk of bacterial growth, PLT storage has been limited to 5 days.The mechanism underlying cold-induced PLT clearance has recently been defined in mice by Hoffmeister and colleagues. 5-7 Briefly, cooling causes clustering of von Willebrand factor receptor complexes ((GPIb ab IX) 2 V) on the PLT surface. Subsequently, a M b 2 integrin receptors (CR3, Mac-1) present on hepatic macrophages recognize the clustered PLT GPIb a molecules, and the hepatic macrophages ingest the PLTs. The critical binding interaction involves a lectin domain of the macrophage a M b 2 integrin receptor that specifically recognizes b-N-acetylglucosamine (b-GlcNAc) residues on PLT GPIb a N-linked oligosaccharides. Coating the PLT b-GlcNAc residues with galactose blocks PLT binding and phagocytosis by macrophages. When transfused into wild-type recipient mice, galactosylated PLTs that have been maintained for 2 hours at 4∞C circulate normally. 7 Modifying PLTs with galactose simply requires incubating PLT-rich plasma with the substrate UDP-galactose; the galactosyltransferase enzyme

Microfluidic Study of Enhanced Deposition of Sickle Cells at Acute Corners

“…In addition, RBCs-WBCs interactions are known to be important in postcapillary venules (32) and WBCs from SCA patients seem to be more adhesive to SRBCs (45) and are capable of forming aggregates of few cells in whole blood (46). Moreover, the drastic morphology change we observe for the aggregate could be correlated to the known activation of platelets observed during blood storage at 4 C (47,48). It has been reported in particular that activated platelets are able to form aggregates in a shear microgradient (49), in locations analogous to the corner of the pillars of this device, but for much higher Reynolds number flow conditions, not relevant for the microcirculation.…”

Platelets: Testing, Dosing and the Storage Lesion—Recent Advances

“…Also, refrigerated platelets could theoretically have functional advantages over room temperature platelets, although this is unproven in vivo. 37 When murine platelets are cooled to 4°C for 2 hours, von Willebrand factor receptor (GPIb) complexes cluster together irreversibly on the platelet surface. In this clustered conformation, platelet GPIb molecules are specifically bound by α M β 2 integrin receptors on liver macrophages.…”

Hemostatic Function of Apheresis Platelets Stored at 4°C and 22°C

“…In recent years, Hoffmeister and colleagues have shown that platelet clearance and function may be entirely separate attributes, and that appropriate modification (such as glycosylation) may prolong platelet survival in circulation (15-17). Concurrent reports from several groups have confirmed that platelets stored at 4°C are “healthier” than platelets stored at room temperature (18). Together, these studies have prompted the reconsideration of cold stored platelets as a transfusion product to treat bleeding patients (18-20).…”