Evaluation of refrigerated platelet concentrates supplemented with low doses of second messenger effectors

Abstract

With the goal of producing haemostatically effective platelet concentrates (PCs) with a longer shelf-life, we aimed to identify a simple combination of platelet inhibitors, with a low pharmacological load, which could avoid the unacceptable loss of platelets stored under refrigerated conditions. PCs stored with different combinations of second messenger effectors were analysed at days 5, 10 and 15 of storage and compared with those supplemented with ThromboSol--a combination of six platelet inhibitors that protects cells from cold damage. The following parameters were analysed: platelet counts, biochemical parameters (glucose, pH, bicarbonate, lactate), cell lysis (lactic dehydrogenase, LDH), membrane glycoproteins (GPs), platelet aggregation, fibrinogen binding and hypotonic shock response. We characterized the combination of amiloride and sodium nitroprusside (at 1/2 the dose included in ThromboSol). This was found to be similar to ThromboSol and superior to nontreated units in the prevention of cold-induced platelet aggregation at day 15 of storage (maintenance of 78% and 80% of initial platelet counts, respectively), preservation of GPIbalpha (11% and 12% better maintenance of mean fluorescence intensity compared with control units, respectively), and reduced cell lysis (13% and 11% decrease in supernatant LDH, respectively). The reduced pharmacological load with the identified solution compared with ThromboSol is an argument in favour of the potential use of these agents when designing strategies to improve PC storage.

Manufacturing variables and hemostatic function of cold‐stored platelets: a systematic review of the literature

“…Of the 33 short‐listed articles that met the eligibility criteria, CSPs were compared to RTPs in 28 (85%) and to temperature‐cycled platelets (TCPs) in two (6%) . No CSP comparisons were performed in three (9%) of the articles .…”

“…Of these, the suspension medium was plasma alone in 19 (68%), plasma plus platelet additive solution (PAS) in 11 (39%), and both media in two articles . A total of 12 (36%) articles described supplementation of the suspension medium with additives (Table ) . Storage bag specification details were included in 21 (64%) articles, of which 20 (95%) reported use of gas‐permeable bags .…”

Cold storage of pooled, buffy‐coat‐derived, leucoreduced platelets in plasma

“…There are several published studies assessing modified storage conditions for platelets to facilitate their storage at 4 ° C. The methods include the addition of uridine diphosphate galactose (UDP-galactose) to modify the platelet surface [8], L -carnitine [9,10] and ThromboSol [11,12]. Suppression of metabolism has been investigated by using either antimycin A in a glucose-free medium [13] or by storing the platelets in a glucose-free medium in a gas impermeable bag [14].…”

Glycans and glycosylation of platelets: current concepts and implications for transfusion

“…In clinical trials, cryopreserved platelets have normal circulation times despite a 50% reduction in recovery and, importantly, superior hemostatic function compared with room temperature-stored platelets [54,55]. Interestingly, ThromboSol, a mixture of six second messenger inhibitors that biochemically stabilizes platelets [56][57][58][59], partly restores the recovery of cryopreserved platelets [60].…”