Decreased sensitivity of human platelets to PGI2 during long-term intraarterial prostacyclin infusion in patients with peripheral vascular disease--a rebound phenomenon?

During successful treatment of peripheral vascular disease with synthetic prostacyclin no alteration in platelet function was reported (1). In 8 patients infused with synthetic prostacyclin continuously for 7 days intraarterially, the platelet function was monitored. Special attention was drawn to the platelet sensitivity in vitro for PGI2, which is discussed as an important factor maintaining the hemostatic balance. In all the patients with peripheral vascular disease between 24 and 48 hours after the beginning of the infusion a sudden decrease in platelet sensitivity accompanied by an increase in platelet count could be seen. These dramatic alterations representing probably a rebound phenomenon occurring during long-term PGI2-treatment might be an explanation for a non-beneficial effect of the treatment and in some cases a limiting factor for the continuation of the infusion itself. It is not clear, if this rebound phenomenon is due to a stimulation of an endogenous inhibitor, lowering the synthesis of a naturally occurring substance acting against this inhibitor or tachyphylaxia.