Platelets stored at 4°C contribute to superior clot properties compared to current standard‐of‐care through fibrin‐crosslinking

Abstract

Summary Currently, platelets for transfusion are stored at room temperature (RT) for 5–7 days with gentle agitation, but this is less than optimal because of loss of function and risk of bacterial contamination. We have previously demonstrated that cold (4°C) storage is an attractive alternative because it preserves platelet metabolic reserves, in vitro responses to agonists of activation, aggregation and physiological inhibitors, as well as adhesion to thrombogenic surfaces better than RT storage. Recently, the US Food and Drug Administration clarified that apheresis platelets stored at 4°C for up to 72 h may be used for treating active haemorrhage. In this work, we tested the hypothesis that cold-stored platelets contribute to generating clots with superior mechanical properties compared to RT-stored platelets. Rheological studies demonstrate that the clots formed from platelets stored at 4°C for 5 days are significantly stiffer (higher elastic modulus) and stronger (higher critical stress) than those formed from RT-stored platelets. Morphological analysis shows that clot fibres from cold-stored platelets were denser, thinner, straighter and with more branch points or crosslinks than those from RT-stored platelets. Our results also show that the enhanced clot strength and packed structure is due to cold-induced plasma factor XIII binding to platelet surfaces, and the consequent increase in crosslinking.

Maximising platelet availability by delaying cold storage

“…Cold storage is known to increase the activation of integrin αIIbβ3 under basal conditions . However, the 4 days of RT storage prior to refrigeration appears to confer some resistance to cold‐induced activation of integrin αIIbβ3.…”

“…Cold storage of platelets is an attractive methodology as it ameliorates many of the issues inherent to RT storage . Studies have shown that platelet refrigeration reduces the risk of bacterial proliferation, decreases platelet metabolic activity and minimises the release of biological response modifiers (BRMs) . Furthermore, cold storage provides the advantage of potentially extending the platelet shelf life .…”

Effect of leukoreduction and pathogen reduction on the hemostatic function of whole blood

“…The rationale for the preference for LTOWB compared to components includes the fact that LTOWB is a more concentrated product compared to reconstituted whole blood (WB) using components (due to increased additive solutions in each component) . LTOWB also contains cold platelets (PLTs) that are more hemostatically active compared to the use of PLTs stored at room temperature when components are used . The risk of bacterial contamination of room temperature PLTs is also greatly reduced with the use of cold‐stored WB.…”

An in vitro pilot study of apheresis platelets collected on Trima Accel system and stored in T‐PAS+ solution at refrigeration temperature (1‐6°C)

“…Over the past decade, cold storage (1‐6°C) of PLTs has generated renewed interest as an alternative to room temperature (RT; 20‐24°C) storage due to its superior preservation of hemostatic function. Compared to RT‐stored PLTs (RTP), cold‐stored PLTs (CSP) have been shown to have better in vitro aggregation response, form stronger clots, maintain mitochondrial function, produce similar amounts of MPs, and respond to physiologic inhibitors (i.e., prostacyclin and nitric oxide) . CSP also have a proven track record in patients, showing acute hemostatic superiority over RTP in individuals with thrombocytopenia, aspirinated volunteers, and in cardiac surgery patients .…”