EFFECTS OF THE NOVEL RECOMBINANT PLASMINOGEN-ACTIVATOR BM-06.022 ON HUMAN PLATELET-AGGREGATION INVITRO

The present study was performed to evaluate effects of the novel recom binant plasminogen activator BM 06.022 on human platelet aggregation. BM 06.022 is an unglycosylated deletion variant of human tissue-type p lasminogen activator. Aggregation was measured in platelet-rich plasma (PRP) from healthy human volunteers in response to adenosine diphosph ate (ADP). Exposure of PRP to BM 06.022 induced a concentration- and t ime-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 p latelet inhibitory effect of BM 06.022 could be reduced or abolished b y aprotinin or chloromethylketone (PPACK), respectively, which is indi cative of a plasmin-dependent mechanism. Concomitant incubation of BM 06.022, acetylsalicylic acid (ASA), and heparin decreased platelet agg regation less than BM 06.022 plus ASA alone, because heparin alone inc reased platelet aggregation. These findings demonstrate an inhibitory effect of BM 06.022 on platelet aggregation in citrated plasma, probab ly at least in part due to a plasmin-dependent mechanism.