Blood Deheparinization Using Immobilized Microbial Heparinase

Linhardt, Robert J.
Langer, R.
Cooney, C.L.
Galliher, P.M.
Flanagan, M.M.
Hoffberg, S.M.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Blood Deheparinization Using Immobilized Microbial Heparinase, R.J. Linhardt, R. Langer, C.L. Cooney, P.M. Galliher, M.M. Flanagan, S.M. Hoffberg, Proceedings of the Second World Congress of Chemical Engineering, Montreal, Canada, Vol. I, pp. 183-185, 1981.
Extracorporeal medical machines (e.g., artificial kidney, pump-oxygenator) perfused with blood have been an effective part of the therapeutic armamentarium for many years. These devices all rely on systemic heparinization to provide blood compatibility. Despite continuous efforts to improve anticoagulation techniques, many patients still develop coagulation abnormalities with the use of these devices (1,2,3). There is the prospect of even longer perfusion times with machines such as the membrane oxygenator. In such cases, the drawbacks of systemic heparinization are multiplied (4). A number of approaches have been attempted to solve this problem. These Include : 1) administration of compounds to neutralize heparin (5), 2) development of heparin substitutes (6), 3) bonding heparin (7-12) or other substances (13) to the extracorporeal device, and 4) development of new blood-compatible materials for construction of the extracorporeal device (14). In spite of these efforts, heparinization continues to be used extensively in all extracorporeal treatments and control of blood heparin levels remains a serious problem. We propose a new approach which would allow the full heparinization of the extracorporeal device yet which could enable elimination on-demand of heparin in the patient's bloodstream. This approach consists of a blood filter containing immobiized heparinase which could be placed at the effluent of any extracorporeal device (Figure 1). Such a filter could theoretically be used to eliminate heparin after it had served its purpose in the extracorporeal device and before it returned to the patient. In this report we discuss our efforts to develop such a filter. Our work has focused on several areas: 1) enzyme production, 2) enzyme purification, 3) characterization of heparinase, 4) immobilization of hepar1nase, and 5) 1n vitro testing of immobilized heparinase.
Proceedings of the Second World Congress of Chemical Engineering, Montreal, Canada, Vol. I, pp. 183-185
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Canadian Society for Chemical Engineering
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
2nd [Second] World Congress of Chemical Engineering
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