Effects of fish-oil constituents and plasma lipids on fibrinolysis in vitro

An association between consumption of fish or fish oils and a reduction in coronary heart disease was established in the 1980s. The mechanisms underpinning this effect have been investigated extensively; with the focus on a reduction in platelet adhesiveness and a lowering of plasma concentrations of low-density lipoprotein (LDL)-cholesterol. Possible effects on fibrinolysis have received less attention and produced conflicting data. The present study evaluates such effects under chemically restricted conditions in vitro, in a system that, based on studies with haemostatically active drugs of known mechanisms, appears to have some relevance to the in vitro situation. Eicosapentaenoic acid (EPA) - one of the major constituents of fish oil - produced a statistically significant (P < 0.05) enhancement of fibrinolysis, when added before formation of the fibrin clot, but generally had the reverse effect when added afterwards. Docosahexaenoic acid (DHA) - the other major constituent of fish oil - had a dramatic inhibitory effect on clot formation, when added prior to clot formation, and inhibited lysis when added after the clot was formed. Maxepa(R) (Seven Seas Ltd.) - a concentrate of EPA and DHA, and the pharmaceutical equivalent of fish oils - did not influence fibrinolysis, when added prior to clot formation. When added after the clot had formed, however, it produced significant (P < 0.05) and dose-dependent effects that varied from enhancement to inhibition. Similarly, both high-density lipoprotein (HDL)- and LDL-cholesterol, when added after clot formation, produced significant (P < 0.05) concentration-dependent effects that varied from enhancement of fibrinolysis (at the lower concentrations tested) to inhibition at higher concentrations. Our findings suggest that the effects of fish oil and lipids are more complex than simple enhancement or inhibition of fibrinolysis. Rather, the benefits may depend both on their concentration and whether they are present before or after the fibrin clots are formed.