Exogenous modification of platelet membranes with the omega‐3 fatty acids DHA and EPA impairs thrombogenesis

Abstract

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with lower risk for adverse cardiovascular events. EPA and DHA‐enhanced platelets exhibit relatively normal platelet aggregation characteristics, suggesting that cardioprotective mechanisms are not inherent to platelet reactivity. We hypothesize that EPA and DHA incorporation hinders platelet‐mediated thrombin production. To this end, platelet membranes were modified by exogenous addition of EPA and DHA to whole blood or platelet‐rich plasma followed by thrombin generation assays. Whole blood treatment inhibited occlusive thrombus formation when perfused over collagen‐coated surfaces compared to matched vehicle controls. EPA and DHA‐treated platelets also showed a kinetic impairment of thrombin generation as measured by both thrombin‐specific substrate conversion and thrombin precursor protein levels in the presence of Factor Xa and prothrombin. A functional deficiency in thrombin production was observed as EPA and DHA‐treated blood formed more diffuse thrombi and less fibrin versus matched controls after perfusion across collagen‐coated surfaces. These results strongly suggest that EPA and DHA impair platelet‐mediated thrombin generation, providing a unique cellular mechanism behind the cardioprotective phenotype seen after increased omega‐3 fatty acid intake. Funded by NIH NCRR 2 P20 RR016479.