Platelet reactivity in platelet concentrates is promoted by short-term refrigeration

Background

The use of cold-stored platelets is discussed to be beneficial for the treatment of acute hemorrhage. Recently, we could show that refrigeration for only 1-2 h was sufficient to increase reactivity of fresh platelets, rendering the opportunity to instantly generate platelets with a higher hemostatic capacity. In this study, we investigated the effect of cold storage for 1 h (CT) in stored apheresis-derived platelet concentrates (APC) after foregoing storage at room temperature (RT).

Methods

APC stored for 1 day or for 2 days at RT, were exposed to cold temperature for 1 h. APC continually stored at RT served as controls. Consecutively, platelet integrity was analyzed by different methods. Inhibitory signaling was explored by vasodilator-stimulated phosphoprotein (VASP) phosphorylation using flow cytometry and by measurement of cyclic nucleotide concentrations. Western Blot analysis was used to investigate activating signaling pathways. Light transmission aggregometry was performed with activators in threshold concentrations.

Results

After cold exposition, VASP phosphorylation levels were partially decreased in APC at storage day 1 and day 2, compared to continued RT storage. Additionally, induced cGMP and cAMP levels were reduced in CT-stored APC. Basal phosphorylation levels of ERK1/2 kinase or p38 MAP kinase were emphasized after cold storage. Aggregation values induced with threshold concentrations of adenosine diphosphate, collagen or TRAP-6 reached higher values in APC after refrigeration for 1 h. In general, cold-mediated effects were more pronounced in APC, stored for 2 days.

Conclusion

In APC at storage day 1 and at storage day 2, exposition to cold temperature for 1 h results in increased platelet reactivity, characterized by an attenuation of inhibitory signaling, by supported activating signaling pathways and by facilitated threshold aggregation responses. Compared to permanently RT-stored APC, short-term refrigeration may be an opportunity to manufacture APC with improved hemostatic capacity "on demand", favorable for the treatment of hemorrhage.

Offenlegung Interessenkonflikt:

The study was supported by the "Stiftung Transfusionsmedizin und Immunhämatologie" of the DGTI.

The authors have no other conflicts of interests to declare.