An Immobilized Microbial Heparinase for Blood Deheparinization

Authors
Linhardt, R. J.
Cooney, C. L.
Tapper, D.
Zannetos, C. A.
Larsen, A. K.
Langer, R.
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
1984-02-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
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).
Abstract
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.
Description
Applied Biochemistry and Biotechnology, 9, 41-55
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Applied Biochemistry and Biotechnology
https://harc.rpi.edu/
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