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Insights into the inhibition of platelet activation by omega-3 polyunsaturated fatty acids: beyond aspirin and clopidogrel
Authors:Cohen Mauricio G  Rossi Joseph S  Garbarino Jennifer  Bowling Regina  Motsinger-Reif Alison A  Schuler Carl  Dupont Allison G  Gabriel Don
Affiliation:aUniversity of Miami Miller School of Medicine, Miami, FL;bThe University of North Carolina at Chapel Hill, Chapel Hill, NC;cInvitrox, Inc. Research Triangle Park, NC;dBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC
Abstract:

Objectives

We sought to examine the effects of escalating doses of omega-3 polyunsaturated fatty acid (PUFA) supplements on platelet function using light transmission aggregometry (LTA) and electrophoretic quasi-elastic light scattering technology (EQELS).

Background

PUFA may inhibit platelet function through fatty acid substitution in the platelet membrane by changing the surface charge density and causing decreased production of thromboxane A2. EQELS can measure platelet surface charge density and determine whether the platelet is in resting or activated state.

Methods

A total of 30volunteers were divided in 3 groups of 10 as follows: Group A, no antiplatelet agent; Group B, daily aspirin only, and Group C, daily aspirin and clopidogrel. All patients received escalating doses of omega-3PUFA from 1 to 8 g daily over 24 weeks. Platelet function was measured by template bleeding time, LTA, and EQELS at baseline and at 6, 12, 18 and 24 weeks.

Results

Mean bleeding time increased in a dose-dependent manner with escalating omega-3 PUFA doses. LTA confirmed expected antiplatelet effects of aspirin and clopidogrel, but did not detect any additional antiplatelet effects of omega-3 PUFA. EQELS showed a significant increase in the negative resting platelet charge compared to baseline and an attenuated response to arachidonic acid mediated platelet activation. No bleeding events were observed.

Conclusions

In this pilot study we were able to successfully measure platelet surface charge variation as a measure of omega-3 PUFA effect on platelets. Our results suggest that omega-3 PUFA increase the total platelet surface charge and, therefore, attenuate platelet activation, even among patients taking aspirin or aspirin plus clopidogrel. Further studies are needed to determine the clinical significance of these measured effects and EQELS results.
Keywords:Abbreviations: PUFA, Polyunsaturated Fatty Acid   EQELS, Electrophoretic quasi-elastic light scattering   LTA, Light transmission aggregometry   DHA, Docosohexaenoic acid   EPA, Eicosapentaenoic acid   INR, International normalized ratio   PRP, Platelet rich plasma   PPP, Platelet poor plasma   ADP, Adenosine diphosphate   AA, Arachidonic acid
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