MODIFICATION OF THE FATTY ACID-INDUCED THROMBOCYTOPENIA BY ANTICOAGULANTS AND COMPOUNDS WHICH INHIBIT IN VITRO PLATELET AGGREGATION

¹ Research Division, Hoffmann-La Roche Inc., Nutley, New Jersey

In an effort to characterize further potential antithrombotic effects of compounds which inhibit platelet aggregation and adhesiveness in vitro, an animal assay system was developed in which the acute and reversible thrombocytopenia following i.v. injection of 2.5 mg/kg of Na laurate was compared in drug-treated and untreated rabbits. Among several antihistamines, antiserotonins, tranquilizing and antinflammatory drugs known to inhibit adenosine diposphate-induced platelet clumping in vitro, only phenylbutazone inhibited Na laurate-induced thrombocytopenia. Large doses were necessary and the effect was not consistent. Three anticoagulants, heparin, bishydroxycoumarin and a new, synthetic heparinoid, Ro 2-7509, inhibited the thrombocytopenic response, but only at doses which also affected blood clotting. Na laurate given after large doses of heparin or Ro 2-7509 often caused platelet clumping, which may be a manifestation of certain thrombogenic properties of the two anticoagulants. Adenosine triphosphate and adenosine monophosphate had no effect on Na laurate-induced thrombocytopenia. Adenosine triphosphate itself caused significant decrease in platelet counts, probably because of its conversion to adenosine diphosphate. It is suggested that the Na laurate-induced thrombocytopenia represents an early and mostly reversible stage of thrombosis which can be influenced by drugs known to have a beneficial effect in thromboembolism in man.