Abstract
To control blood levels of heparin during extracorporeal therapy, the use of a blood filter containing heparinase, a heparin-specific enzyme that cleaves heparin to small fragments with less anticoagulant activity, has been proposed. These fragments have anti-factor Xa activity but no anti-thrombin activity. The potential toxicity of heparin fragments as compared to heparin was examined in rats by identifying presumptive sites of drug-related toxicity by whole-body autoradiography and by histological examination of major organs. Radioautograms of rats sacrificed 5 hr after dosing with [ 35S]heparin fragments indicated no potential targets different from what was observed in rats dosed with [ 35S]heparin. In addition, the faster urinary clearance of heparin fragments resulted in a lower concentration of these fragments than of heparin in all common target organs. No hemorrhages or other lesions were found in rats injected intravenously with heparin fragments (100 mg/kg) and sacrificed after 5 hr. In addition, no mortality or delayed toxic effects were observed in a similar group of animals sacrificed 2 weeks after dosing. In contrast, 80% of rats injected with heparin (100 mg/kg) showed hemorrhages of the lungs at the time of necropsy.
Published Version
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