Abstract
Of great concern in medical surgery is the formation of blood clots, such as, deep vein thrombosis (DVT) with possible emboli reaching the lungs, thus diminishing or shutting down the oxygen transport to tissue processes. Our research has focused on producing an inexpensive protein C product via IMAC that could be used to bring blood levels to normal. Our work has emphasized safety for hereditary and acquired protein C deficient patients in all aspects of life. There are presently two expensive protein C products on the market. One is Xigris (activated protein C) produced by Eli Lilly & Co., and the second is Ceprotin, the zymogen product which is being manufactured by Baxter BioPharmaceuticals. I will be a guinea pig for my own research hypothesis in that I will have total hip replacement surgery using Ceprotin to help prevent blood clotting due to a protein C deficiency. It is difficult for surgeons and hematologists to agree on a safe procedure for protein C deficient patients undergoing major surgery. The hematologist is concerned about the potential for DVT and lung emboli, while the surgeon is also concerned about internal bleeding and infection after the surgery. The established approach would involve high doses of low molecular weight heparin (LMWH) for protein C deficient patients which would be unacceptable to the surgeon. My hypothesis has recommended administration of zymogen protein C to simulate a normal blood condition where the standard protocol could be used. The validity of this hypothesis is soon to be tested.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
H.I. Bicher., Bruley, D. F., and M. H. Knisely, “Anti-Adhesive Drugs and Tissue Oxygenation,” edited by D. F. Bruley and H. I. Bicher, Advances in Experimental Medicine and Biology, Plenum, Press, Vol. 37B657-667, 1973.
D.F.Bruley. and W. N. Drohan, “Protein C and Related Anticoagulants,” Advances in Applied Biotechnology Series, Volume 11, Gulf Publishing Company (Portfolio Publishing Company), 1990.
G.R. Sharma., Gerlitz, G., Berg, D.T., Cramer, M.S., Jakubowski, J.A., Galbreath, E.J., Heuer, J.G., and B.W.Grinnell, “Activated Protein C Modulates Chemokine Response, and Tissue Injuiry in Expereimental Sepsis”, Advances in Experimental Medicine and Biology, Vol. 614, pp.83-91, Springer, 2008.
D.F.Bruley, Hereditary protein C deficiency, ENCH 444 Class Handout, 1996.
P.C.Comp., “The clinical potential of protein C and activated protein C, advances in applied biotechnology series: protein C and related anticoagulants,” edited by D. F. Bruley and W. Drohan (Portfolio Publ. Co., Texas, 1990), vol. 11.
D.F.Bruley, Hereditary protein C deficiency, ENCH 444 Class Handout, 1996.
R.Drews., et al., Proteolytic maturation of protein C upon engineering the mouse mammary gland to express furin, Proc. Natl. Acad. Sci. USA 92, 10462 (1995).
D.B.McClure., et al., Post-translational processing events in the secretion pathway of human protein C, a complex vitamin K-dependent antithrombotic factor, J. Bio. Chem. 267(27), 19710 (1992).
C.T.Esmon., The roles of protein C and thrombomodulin in the regulation of blood coagulation, J. Bio. Chem. 264 (9), 4743 (1989).
C.M.Henkens., et al., Plasma levels of protein S., protein C, and factor X; Effects of sex, hormonal state and age, Thrombosis and Haemostasis 74 (1995).
T.Mather., et al., The 2.8 Å crystal structure of Gla-domainless activated protein C, EMBO J. 15(24), 6822 (1996)
C.T.Esmon., The regulation of natural anticoagulant pathways, Science 235, 1348 (1997).
A.R.Rezaie and C. T. Esman, Tryptophan 231 and 234 in protein C report the Ca2+-dependent conformational change required for activation by the thrombin-thrombomodulin complex, Biochemistry 34, 12221 (1995).
Sigma Chemical Company (1997): http://www.sigmaaldrich.com.
C.T.Esmon., Regulation of coagulation: The nature of the problem, in: Protein C and Related Coagulants, edited by D. F. Bruley and W. N. Drohan (Gulf, Houston, 1990), p. 3.
C.I.Fisher., et al., Models of the serine domain of the human antithrombotic plasma factor (1994).
D.C.Foster., et al., The nucleotide sequence of the gene for human protein C, Proc. Natl. Acad. Sci. USA 82, 4673 (1985).
L.V.Medved., et al., Thermal stability and domain-domain interactions in natural and recombinant protein C, J. Bio. Chem. 270(23), 13659 (1995).
C.L.Orthner., et al., Conformational changes in an epitope localized to the NH2-terminal region of protein C, J. Bio. Chem. 2647(31), 18781 (1989).
B.W.Grinnell., et al., Trans-activated expression of fully gamma carboxylated recombinant human protein C, an antithrombotic factor, Bio/Technology 5, 1189 (1987).
S.C.B.Yan., et al., Post-translational modifications of proteins; some problems left to solve, TIBS 14, 264 (1989).
D.F.Bruley., Protein C – The Ultimate Anticoagulant/Antithrombotic?, in: Anticoagulant, Antithrombotic, and Thrombolytic Thearapeutics II, edited by C. A. Thibeault and L. M. Savage (IBC Library Series, Southborough, MA, 1998).
H.Wu and D. F. Bruley, Chelator, metal ion and buffer studies for protein C separation, Comparative Biochemistry and Physiology Part A 132, 213 (2002).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science+Business Media, LLC
About this paper
Cite this paper
Bruley, D.F. (2009). Zymogen Protein C Concentrate for Safer Heterozygote Surgery, “I am a Guinea Pig!”. In: Liss, P., Hansell, P., Bruley, D.F., Harrison, D.K. (eds) Oxygen Transport to Tissue XXX. Advances in Experimental Medicine and Biology, vol 645. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-85998-9_18
Download citation
DOI: https://doi.org/10.1007/978-0-387-85998-9_18
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-85997-2
Online ISBN: 978-0-387-85998-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)