Deletion of 12-lipoxygenase normalizes platelet function after storage and transfusion in thrombocytopenic mice

Abstract

ObjectivePlatelets for transfusion are stored for 5-7 days. During storage, platelets undergo numerous detrimental functional changes. In the current study, we sought to understand how genetic deletion of 12 –lipoxygenase (12-LOX) affects platelets during storage, before, and after transfusion.Approach and ResultsWe obtained platelets from wild-type (WT) and 12-LOX-/-mice and performed storage studies for 24 and 48 hours. Using LC-MS/MS-MRM, we showed that ω-3 and ω-6 fatty acids increased significantly in stored platelets from 12-LOX-/-mice, while oxylipins were significantly lower than in WT platelets. The circulation time of fresh 12-LOX-/-platelets was significantly shorter than that of fresh WT platelets, but no differences were observed after storage. Baseline αIIbβ3 integrin activation was significantly lower before and after 24 hours of storage in 12-LOX-/-platelets than in WT platelets. Surprisingly, after transfusion, we observed more baseline αIIbβ3 integrin activation in 12-LOX-/-platelets than in WT platelets. In line with this, transfusion of stored 12-LOX-/-platelets led to more frequent and significantly faster vessel occlusions than transfusion of stored WT platelets in a FeCl3-induced carotid artery injury model in thrombocytopenic mice.ConclusionDeleting 12-LOX improves the post-transfusion function of stored murine platelets. Pharmacologic inhibition of 12-LOX or dietary alterations of ω-3 and ω-6 PUFAs could significantly enhance human platelet quality and function after storage. Future studies must determine the feasibility and safety of 12-LOX inhibition in stored and transfused human platelets.