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Dihomo-γ-linolenic acid (DHLA; Ro 12–1989, Roche), a natural precursor of prostaglandin E1, has been evaluated as a potential antithrombotic agent by studying its effects on platelet function, blood coagulation and blood viscosity. In vitro investigations were performed on blood obtained from 10 normal subjects and 10 patients with diabetes mellitus, 8 of whom had evidence of severe microangiopathy. Prior incubation of normal platelets with DHLA caused a marked and dose-related inhibition of : platelet aggregation in response to stimulation with ADP, collagen, epinephrine, thrombin and ristocetin; platelet glass-bead retention; release of serotonin and platelet factors 3 and 4. Effects on diabetic platelets were less marked but still highly significant. DHLA also reversed platelet aggregation and inhibited the adhesion of porcine platelets to collagen-coated glass. No significant effects were found on whole-blood viscosity or tests of blood coagulation apart from a slight shortening of the one-stage prothrombin time. Ex vivo studies were performed on 3 normal volunteers after oral administration of single doses of DHLA. Increased plasma DHLA/arachidonic acid ratios resulted in all instances (Stone et al, this meeting). No adverse effects were noted but consistent evidence of a favourable change in haemostatic tests was not obtained. The spectrum of in vitro inhibitory activity of DHLA on platelets is wider than that reported for other potential anti-thrombotic agents and our results suggest that DHLA shows considerable promise in this respect.

The Antithrombotic Potential of Dihomo-γ-Linolenic Acid