Interactions between prostacyclin analogue ZK 36374 and heparin in their effects upon platelet function

Abstract

Prostacyclin and heparin can be administered to patients concurrently, with the aim of maximizing anticoagulant effect. It has been suggested that the two agents may interact in their effects upon platelet function. We have therefore studied this parameter in the presence of ZK 36374, a chemically stable analogue of prostacyclin and heparin, alone and in combination. Platelet responses to ADP and thrombin have been studied by standard aggregometry, and intra-platelet calcium mobilization has simultaneously been recorded after loading the cells with the fluorescent calcium indicator, Quin 2. ZK 36374 alone consistently inhibited platelet aggregation and calcium mobilization in response to ADP and thrombin, in a dose-dependent fashion. Heparin alone did not significantly alter the responses to ADP but consistently reduced those to thrombin. Pre-mixture of ZK36374, with heparin, was shown to interfere with the ability of the prostacyclin analogue to inhibit platelet aggregation and calcium flux in response to ADP. In contrast, ZK 36374 inhibition of platelet responses was markedly enhanced when thrombin was the agonist.