title: Safer surgery using zymogen protein C concentrate.
abstract: This is the first case (November 12, 2007) of peri-operative use of zymogen protein C (ZPC) for a heterozygote Protein C deficient (50%) patient with heterozygosity for the prothrombin gene mutation. The surgery involved total left hip replacement. The patient was 74 years of age and at very high-risk for Deep Vein Thrombosis (DVT) thus possible lung emboli. He was a survivor of Venous thrombo-embolism (VTE) in 1999.For this case the need for increased heparin to prevent a reoccurrence of thrombosis led to a further concern of internal bleeding and possible infection. As proposed by the authors in previous publications the use of a ZPC concentrate would decrease the chance of a thrombosis, with minimum or no internal bleeding. ZPC is activated at the endothelium cell surface and on the surface of the platelets where and when it is needed, therefore providing a safer procedure.This protocol was implemented by administering ZPC concentrate 1 day prior to surgery and continuing for 10 days after. Slightly higher than normal blood loss occurred, however, a safe procedure was achieved without dangerous side effects while several additional benefits were experienced (level of PC activity as high as 235% above normal were measured during the procedure.). It is felt that positive effects were the result of increased blood flow and oxygen transport to the tissues by reducing blood sludging in the microcirculation. Further studies on Protein C dose levels will be necessary to provide economical, safe and efficacious use of Protein C products.It is suggested that ZPC should be considered for patients with high probability of VTE which could cause thrombotic occlusion of the pulmonary and peripheral vasculature. These phenomena can result in hypoxia and hypo perfusion causing organ failure and death.Our research includes a focused effort to optimize upstream and downstream bio-processing to produce both zymogen and activated Protein C at a lower cost and to examine the medical indications that could benefit from a more available and affordable Protein C product.
authors.affiliation: Synthesizer, Inc., 2773 Westminster Road, Ellicott City, MD 21043, USA. bruley@umbc.edu
authors.forename: Duane F
authors.initials: DF
authors.lastname: Bruley
authors.forename: Simon C
authors.initials: SC
authors.lastname: Mears
authors.forename: Michael B
authors.initials: MB
authors.lastname: Streiff
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000379:methods*; D004792:Enzyme Precursors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011486:Protein C / Q000494:pharmacology*
chemical_list: D004792:Enzyme Precursors; D011486:Protein C