Eicosanoids, other fatty acid metabolites and the cardiovascular system: are the present antithrombotic approaches rational?

Antiplatelet +/- anticoagulant drugs are currently used as the standard treatment to prevent and treat thrombosis. While this approach is beneficial, it is not optimal. Recent evidence suggests that constituents of the vascular endothelium play an important role in regulating vessel wall thrombogenecity, thereby inhibiting thrombogenesis. These include constituents such as PGI2, tissue plasminogen activator, thrombomodulin and the lipoxygenase fatty acid metabolite derived from linoleic acid, 13-hydroxyoctadecadienoic acid (13-HODE). Consequently, new strategies have been developed to maximize the use of these agents for antithrombotic therapy. We will review these different approaches, discuss their rationale, and based upon recent experimental data, introduce an alternative approach for antithrombotic therapy which may circumvent a number of limitations and side-effect of the currently used drugs.