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bioRxiv · 10.1101/2022.09.23.509265

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

Larsen, H.·Byrne, D. A.·Bailey, S.·Stolla, M. C.·Holinstat, M.·Fu, X.·Stolla, M.
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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 {omega}-3 and {omega}-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 IIb{beta}3 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 IIb{beta}3 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 {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.

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Larsen, H., Byrne, D. A., Bailey, S., Stolla, M. C., Holinstat, M., Fu, X., Stolla, M.. 2022-09-26. Deletion of 12-lipoxygenase normalizes platelet function after storage and transfusion in thrombocytopenic mice. https://doi.org/10.1101/2022.09.23.509265

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