Amelioration of lesions associated with 24-hour suboptimal platelet storage at 16°C by a p38MAPK inhibitor, VX-702.

Abstract

Previous studies with p38MAPK inhibitors at room temperature demonstrated that they improve a large number of platelet storage parameters, but cannot substantially inhibit p38MAPK activation nor protect against widespread decrements in platelet quality parameters during 4 °C storage. In this study, platelet quality parameters and inhibition of p38MAPK by VX-702 were studied after incubation of platelets at 16 °C without agitation, suboptimal storage conditions which produce moderate platelet decrements. Trima apheresis units were collected and aliquoted into three 60-ml CLX storage bags: (i) a control aliquot which was held at 20-24 °C with constant agitation; (ii) a test aliquot which was held at 20-24 °C with agitation until Day 2, when it was reincubated at 16 ± 1 °C for 24 ± 0·5 h without agitation and then returned 20-24 °C with agitation; (iii) a test aliquot containing 1 μm VX-702 stored in an identical fashion as aliquot 2. Aliquots were tested for an array of platelet storage parameters and p38MAPK activation on Days 1, 4 and 7. Many platelet storage parameters and p38MAPK activation were adversely affected by 24-h incubation at 16 °C without agitation. With the exception of ESC, addition of VX-702 prevented p38MAPK activation and the decrements in most observed parameters. Unlike 4 °C storage, VX-702 prevents activation of p38MAPK and decrements in many platelet storage parameters after exposure to 16 °C without agitation for 24 h.