DOI: 10.1161/01.cir.95.4.800. Antithrombotic Potency of Hirudin Is Increased in Nonhuman Primates by Fibrin Targeting

Antithrombotic Potency of Hirudin Is Increased in Nonhuman Primates by Fibrin Targeting

10.1161/01.cir.95.4.800

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation (276)

Abstract

Background Inhibition of thrombin by either the indirect thrombin inhibitor heparin or by more potent direct thrombin inhibitors such as hirudin reduces thrombus formation after arterial injury. The present study was designed to determine if a fibrin-specific thrombin inhibitor could, by local thrombin inhibition, prevent thrombosis more effectively. Methods and Results We first studied antithrombotic potency in vitro, comparing fibrin-targeted hirudin (recombinant hirudin covalently linked to the Fab′ fragment of the anti-fibrin monoclonal antibody 59D8) to recombinant hirudin in baboon plasma. Fibrin-targeted hirudin was nine times more effective than recombinant hirudin in inhibiting fibrin deposition on experimental clot surfaces in baboon plasma ( P <.01). The potency of fibrin-targeted hirudin was then compared with that of recombinant hirudin in a baboon model of thrombus formation. 111 In-labeled platelet deposition was measured in a synthetic graft segment of an extracorporeal arteriovenous shunt in control animals and in animals receiving either fibrin-targeted hirudin or hirudin. In these experiments, fibrin-targeted hirudin was 10-fold more potent than hirudin in inhibiting platelet deposition and thrombus formation ( P <.05). Conclusions These data indicate that targeting a thrombin inhibitor such as hirudin to an epitope present in thrombi results in increased antithrombotic potency.

Bibliography

Bode, C., Hanson, S. R., Schmedtje, J. F., Haber, E., Mehwald, P., Kelly, A. B., Harker, L. A., & Runge, M. S. (1997). Antithrombotic Potency of Hirudin Is Increased in Nonhuman Primates by Fibrin Targeting. Circulation, 95(4), 800â804.

Authors 8

Christoph Bode (first)
Stephen R. Hanson (additional)
John F. Schmedtje (additional)
Edgar Haber (additional)
Petra Mehwald (additional)
Andrew B. Kelly (additional)
Laurence A. Harker (additional)
Marschall S. Runge (additional)

References 21 Referenced 15

10.1161/circ.90.5.7955205
10.1055/s-0038-1649939
10.1097/00005344-199402000-00005
10.1161/01.CIR.89.4.1557
10.1016/0735-1097(95)00104-C
Gold HK Yasuda T Jang IK Guerrero JL Fallon JT Leinbach RC Collen D. Animal models for arterial thrombolysis and prevention of reocclusion: erythrocyte-rich versus platelet-rich thrombus. Circulation. 1991;83(suppl IV):IV-26-IV-40.
10.1161/circ.83.3.1900222
10.1161/circ.90.4.7923645
10.1161/circ.94.5.911
10.1161/circ.90.4.7923646
10.1161/circ.90.4.7923685
10.1073/pnas.84.21.7659
10.1126/science.4023710
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10.1161/circ.94.6.1412
Cadroy Y, Horbett TA, Hanson SR. Discrimination between platelet-mediated and coagulation-mediated mechanisms in a model of complex thrombus formation in vivo. J Lab Clin Med.. 1989;113:436-448. / J Lab Clin Med. (1989)
Cadroy Y, Harker LA, Hanson SR. Inhibition of platelet-dependent thrombosis by low molecular weight heparin (CY222): comparison with standard heparin. J Lab Clin Med.. 1989;114:349-357. / J Lab Clin Med. (1989)

Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:41 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 12:55 p.m.)
Indexed	1 year, 3 months ago (May 12, 2024, 8:07 p.m.)
Issued	28 years, 6 months ago (Feb. 18, 1997)
Published	28 years, 6 months ago (Feb. 18, 1997)
Published Print	28 years, 6 months ago (Feb. 18, 1997)

Funders 0

None

BibTeX

@article{Bode_1997, title={Antithrombotic Potency of Hirudin Is Increased in Nonhuman Primates by Fibrin Targeting}, volume={95}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/01.cir.95.4.800}, DOI={10.1161/01.cir.95.4.800}, number={4}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Bode, Christoph and Hanson, Stephen R. and Schmedtje, John F. and Haber, Edgar and Mehwald, Petra and Kelly, Andrew B. and Harker, Laurence A. and Runge, Marschall S.}, year={1997}, month=feb, pages={800–804} }

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