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(Circulation. 2002;106:261.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Antithrombin-Heparin Covalent Complex

A Possible Alternative to Heparin for Arterial Thrombosis Prevention

Anthony K.C. Chan, MBBS^*; Janusz Rak, MD, PhD^*; Leslie Berry, BSc^*; Peng Liao, MD; Michal Vlasin, DVM, PhD; Jeffrey Weitz, MD; Petr Klement, DVM, PhD

From Henderson Research Centre, McMaster University, Hamilton (all authors), and the Hospital for Sick Children, Toronto (A.K.C.C.), Ontario, Canada; and the University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic (M.V., P.K.).

Correspondence to Petr Klement, DVM, PhD, 711 Concession St, Hamilton, Ontario, Canada, L8V 1C3. E-mail pklement{at}thrombosis.hhscr.org

Background— The anticoagulant effect of heparinoids is attributed to their cofactor activity for antithrombin (AT) and heparin cofactor II. In patients with thrombosis, however, thrombin is often protected from AT-dependent, heparin-mediated inactivation. The purpose of this study was to compare the properties of unfractionated/standard heparin (UFH/SH) and those of a novel covalent AT-heparin complex (ATH) in a rabbit arterial thrombosis prevention and bleeding model.

Methods and Results— Thrombosis in the distal aorta was triggered by vessel wall injury and critical stenosis. Blood flow in the damaged arterial segment was monitored with a flow probe placed distal to the constrictor. Rabbits were given doses of SH (62.5 to 187.5 IU · kg^-1 · 90 min^-1) or ATH (16 to 65 IU · kg^-1 · 90 min^-1). Cumulative blood loss from skin incisions was used to assess drug safety. The antithrombotic effects of ATH were greater than those of SH as measured by clot weight, blood flow, and vessel patency; eg, complete thrombus resolution was achieved with ATH (33 to 65 IU/kg), but not SH (125.0 to 187.5 IU/kg). At doses that produced equivalent vessel patency (50% to 60%), blood loss induced by ATH (60.2 µL) was 2.6-fold lower (P<0.05) than that induced by SH (154.6 µL).

Conclusions— In our experimental system, ATH was able to control arterial thrombosis more effectively than its SH precursor, without pronounced bleeding.

Key Words: coronary disease • thrombosis • heparin • fibrin

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