Activation and impairment of platelet function in vitro by fatty acid ethyl ester, a nonoxidative ethanol metabolite: effect of fatty acid ethyl esters on human platelets.
BACKGROUND
The goal of this study was to investigate the effect of fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, on platelet function. We hypothesized that FAEE increase the risk of bleeding by producing an alteration in platelet membrane structure or function.


METHODS
Isolated human platelets incubated with FAEE were prepared and multiple assays for platelet activation were performed; beta-thromboglobulin release from platelet granules, platelet aggregation, arachidonate release from phospholipids, and intracellular cyclic AMP (cAMP) levels. We examined also the combined effect of epinephrine and FAEE on platelet aggregation.


RESULTS
FAEE induced platelet shape change, release of alpha granules and release of arachidonate from phospholipids without an increase in eicosanoid production and decreased cAMP levels. The platelets did not aggregate in response to FAEE alone, but did shorten the time to maximum aggregation with epinephrine.


CONCLUSIONS
These studies show that FAEE potentiate platelet activation but do not induce aggregation, presumably because they do not stimulate thromboxane A(2) production.
Salem
Raneem O
RO
Division of Laboratory Medicine, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Laposata
Michael
M
D000244:Adenosine Diphosphate; D016718:Arachidonic Acid / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine; D004952:Esters / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009829:Oleic Acids / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D013928:Thromboxane A2 / Q000097:blood; D013997:Time Factors; D001620:beta-Thromboglobulin / Q000378:metabolism
D002492:Central Nervous System Depressants; D004952:Esters; D005227:Fatty Acids; D009829:Oleic Acids; D001620:beta-Thromboglobulin; D016718:Arachidonic Acid; D000431:Ethanol; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D004837:Epinephrine; C033180:ethyl oleate