An Immobilized Microbial Heparinase for Blood Deheparinization

Linhardt, R. J.
Cooney, C. L.
Tapper, D.
Zannetos, C. A.
Larsen, A. K.
Langer, R.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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An Immobilized Microbial Heparinase for Blood Deheparinization, R.J. Linhardt, C.L. Cooney, A. Larsen, C.A. Zannetos, D. Tapper, R. Langer, Applied Biochemistry and Biotechnology, 9, 41-55 (1984).
A new medical application of an immobilized microbial enzyme is described. Extracorporeal devices require systemic heparin administration to prevent thrombus formation; however, the use of heparin often leads to serious hemorrhagic complications. Heparinase isolated from Flavobacterium has been immobilized and used in a fluidized bed reactor to eliminate heparin from blood passing through an extracorporeal circuit both in vitro and in vivo. This paper discusses the stepwise development of this heparinase reactor including: (1) improvements in the fermentation resulting in an inexpensive large-scale source of heparinase without the addition of the previously required inducer, heparin; (2) the use of batch processes to adapt previous purification schemes to large-scale heparinase production and the subsequent purification of heparinase to a single SDS-PAGE banding protein; (3) the immobilization of heparinase with a 91% activity recovery and good stability, (4) the design and successful testing of a fluidized bed reactor containing immobilized heparinase in the removal of clinically used quantities of heparin from both human blood in vitro and canine blood in vivo; and (5) the initiation of animal studies focusing on the toxicology of heparinase-derived heparin degradation products and the short and long term effects of exposure to these products and to heparinase.
Applied Biochemistry and Biotechnology, 9, 41-55
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
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Rensselaer Polytechnic Institute, Troy, NY
Applied Biochemistry and Biotechnology