Effects of riboflavin and ultraviolet light treatment on platelet thrombus formation on collagen via integrin αIIbβ3 activation

Abstract

The adoption of pathogen reduction technology (PRT) is considered for the implementation of safer platelet (PLT) transfusion. However, the effects of PRT treatment on PLT thrombus formation under blood flow have not yet been fully clarified. Leukoreduced PLT concentrates (PCs) obtained by plateletpheresis were treated with riboflavin and ultraviolet light (Mirasol PRT). PC samples were passed through a column filled with collagen-coated beads at a fixed shear rate after 1, 3, and 5 days of storage. The thrombus formation ability was evaluated by measuring collagen column retention rate. The change in the activation state of integrin αIIbβ3 on PLTs during storage was examined by flow cytometry. The retention rate of the PRT-treated PLTs was significantly higher than that of the control PLTs on the day of treatment and decreased with storage but remained higher than those of the control during storage. This modification did not correlate with the total αIIbβ3 or fibrinogen binding on the PLTs but correlated significantly with PAC-1 binding. Mn(2+) -induced αIIbβ3 activation also fully restored the retention rate in the Day 5 PRT-treated PLTs along with the increase in PAC-1 binding. Riboflavin-based PRT treatment of PCs leads to the enhancement of thrombus formation on collagen, which is related to the activation status of αIIbβ3, which does not bind to fibrinogen but binds to PAC-1. The impact of this finding on the hemostatic or even thrombogenic potential in vivo must await clinical evaluation.