Platelet-activating factor (PAF), a mediator of platelet aggregation. Effect of corticosteroids on PAF-induced platelet aggregation

Platelet-activating factor has been shown to be a mediator of inflammation, which causes platelet activation independently from ADP-, and arachidonic acid-mediated pathways. The infusion of PAF into rabbits caused an acute but reversible thrombocytopenia similar to that occurring during IgE-induced systemic anaphylaxis or after injection of immune-complexes. We have studied the effect of membrane active drugs and corticosteroids on platelet aggregation induced by PAF. Xilocaine, mepacrine, reserpine, imipramine were strong inhibitors of PAF-induced platelet aggregation similarly to 6-methyl prednisolone and hydrocortisone. Furthermore, 6-methyl prednisolone prevented in vivo PAF-induced thrombocytopenia in the rabbit. Our studies demonstrate that corticosteroids are inhibitors of PAF action in vivo and in vitro and provide a plausible rationale for the empiric observation that high dose corticosteroids may be beneficial in patients with thrombocytopenia occurring in anaphylactic shock and the acute phase of lupus erythematosus systemicus.