Effects of the novel recombinant plasminogen activator BM 06.022 on human platelet aggregation in vitro

Abstract

The present study was performed to evaluate effects of the novel recombinant plasminogen activator BM 06.022 on human platelet aggregation. BM 06.022 is an unglycosylated deletion variant of human tissue-type plasminogen activator. Aggregation was measured in platelet-rich plasma (PRP) from healthy human volunteers in response to adenosine diphosphate (ADP). Exposure of PRP to BM 06.022 induced a concentration-and time-dependent reduction of platelet aggregation compared with vehicle-control experiments. Incubation of high (3200 U/ml) concentrations of BM 06.022 for 0 to 15 min did not increase platelet aggregation. The platelet inhibitory effect of BM 06.022 could be reduced or abolished by aprotinin or chloromethylketone (PPACK), respectively, which is indicative of a plasmin-dependent mechanism. Concomitant incubation of BM 06.022, acetylsalicylic acid (ASA), and heparin decreased platelet aggregation less than BM 06.022 plus ASA alone, because heparin alone increased platelet aggregation. These findings demonstrate an inhibitory effect of BM 06.022 on platelet aggregation in citrated plasma, probably at least in part due to a plasmin-dependent mechanism.