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

Objective Platelets for transfusion are stored for 5 to 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 Results We obtained platelets from wild-type (WT) and 12-LOX KO mice and performed storage studies for 24 and 48 hours. Using LC-MSMS MRM, we showed that OMEGA 3 and OMEGA 6 fatty acids increased significantly in stored platelets from 12 LOX KO mice, while oxylipins were significantly lower than in WT platelets. The circulation time of fresh 12 LOX KO platelets was significantly shorter than that of fresh WT platelets, but no differences were observed after storage. Baseline alphaIIbBETA3 integrin activation was significantly lower before and after 24 hours of storage in 12 LOX KO platelets than in WT platelets. Surprisingly, after transfusion, we observed more baseline alphaIIbBETA3 integrin activation in 12 LOX KO platelets than in WT platelets. In line with this, transfusion of stored 12-LOX KO 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. Conclusion Deleting 12 LOX improves the post-transfusion function of stored murine platelets. Pharmacologic inhibition of 12 LOX or dietary alterations of OMEGA 3 and OMEGA 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. ### Competing Interest Statement The authors have declared no competing interest.