Hugh O'Brodovich

Publication Details

  • Covalent antithrombin-heparin complexes with high anticoagulant activity - Intravenous, subcutaneous, and intratracheal administration JOURNAL OF BIOLOGICAL CHEMISTRY Chan, A., Berry, L., OBRODOVICH, H., Klement, P., Mitchell, L., Baranowski, B., Monagle, P., Andrew, M. 1997; 272 (35): 22111-22117

    Abstract:

    Although heparin has been used clinically for prophylaxis and treatment of thrombosis, it has suffered from problems such as short duration within compartments in vivo that require long term anticoagulation. A covalent antithrombin-heparin complex has been produced with high anticoagulant activity and a long half-life relative to heparin. The product had high anti-factor Xa and antithrombin activities compared with noncovalent mixtures of antithrombin and heparin (861 and 753 units/mg versus 209 and 198 units/mg, respectively). Reaction with thrombin was rapid with bimolecular and second order rate constants of 1.3 x 10(9) M-1 s-1 and 3.1 x 10(9) M-1 s-1, respectively. The intravenous half-life of the complex in rabbits was 2.6 h as compared with 0.32 h for similar loads of heparin. Subcutaneous injection of antithrombin-heparin resulted in plasma levels (peaking at 24-30 h) that were still detectable 96 h post-injection. Given the increased lifetime in these vascular and intravascular spaces, use of the covalent complex in the lung was investigated. Activity of antithrombin-heparin instilled into rabbit lungs remained for 48 h with no detection of any complex systemically. Thus, this highly active agent has features required for pulmonary sequestration as a possible treatment for thrombotic diseases such as respiratory distress syndrome.

    View details for Web of Science ID A1997XT85000066

    View details for PubMedID 9268354

Stanford Medicine Resources:

Footer Links: