caa a22 4500 475824679 CHVBK 20180406123828.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1023/A:1018722828543 doi (NATIONALLICENCE)springer-10.1023/A:1018722828543 Combination of a Direct Thrombin Inhibitor and a Platelet Glycoprotein IIb/IIIa Blocking Peptide Facilitates and Maintains Reperfusion of Platelet-Rich Thrombus with Alteplase [Elektronische Daten] [Marc Sabatine, Thomas Tu, Ik-Kyung Jang] We sought to determine the efficacy of the combination of argatroban, a direct thrombin inhibitor, and G4120, a platelet glycoprotein (GP) IIb/IIIa blocker, to enhance thrombolysis with alteplase. Platelet-rich thrombus in the rabbit arterial thrombosis model is relatively resistant to alteplase despite the addition of aspirin and heparin. The adjunctive use of either direct thrombin inhibitors or GP IIb/IIIa inhibitors in thrombolysis has been investigated with encouraging, but limited, success. The usefulness of combining both agents as adjunctive therapy to thrombolysis has not been fully explored. Following platelet-rich thrombus formation in the rabbit, argatroban (3 mg/kg), G4120 (0.5 mg/kg), G4120 plus heparin (200 U/kg), or G4120 plus argatroban were intravenously infused over 60 minutes. Alteplase was given as intravenous boluses (0.45 mg/kg) at 15-minute intervals up to 4 doses or until reperfusion. Blood flow and bleeding time were monitored for 2 hours. The combination of G4120 plus argatroban resulted in a persistent patency in 5 of 7 animals compared with 0 of 6 for argatroban alone (p=0.02), 1 of 6 for G4120 alone (p=0.08), and 2 of 6 for G4120 plus heparin (p=0.2). Although during the infusion the bleeding times were longer in the groups that received G4120 (26±7.7 minutes vs. 14±10 minutes, p<0.05), by the end of the experiment there were no statistically significant differences. Similarly, during the infusion the activated partial thromboplastin times (aPTT) was higher in groups that received heparin or argatroban (99±51 seconds vs. 32±7.6 seconds, p<0.001), but by the end of the experiment the aPTTs had returned to close to baseline in all groups except the G4120 plus heparin group. These results suggest that lysis of platelet-rich thrombus with alteplase requires the addition of both potent platelet and thrombin inhibitors. Specifically designed agents, G4120 and argatroban, are effective without additional increased risk for bleeding. Kluwer Academic Publishers, 2000 alteplase nationallicence argatroban nationallicence GP IIb/IIIa inhibitor nationallicence thrombolysis nationallicence Sabatine Marc Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA aut Tu Thomas Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA aut Jang Ik-Kyung Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA aut Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/2(2000-10-01), 189-196 0929-5305 10:2<189 2000 10 11239 https://doi.org/10.1023/A:1018722828543 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1018722828543 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sabatine Marc Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- Tu Thomas Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- Jang Ik-Kyung Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA aut NATIONALLICENCE 773 0- Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/2(2000-10-01), 189-196 0929-5305 10:2<189 2000 10 11239 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer