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DOI: 10.1055/s-0038-1660995
The Use of a Functional and Immunologic Assay for Plasma Protein C in the Study of the Heterogeneity of Congenital Protein C Deficiency
Publication History
Received 30 August 1983
Accepted 12 October 1983
Publication Date:
19 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/198401/lookinside/thumbnails/10-1055-s-0038-1660995-1.jpg)
Summary
Protein C is a vitamin K dependent protein involved in blood coagulation. A congenital deficiency in protein C antigen - which inherits as an autosomal dominant disorder - has been reported to be associated with a high risk for thrombo-embolic disease at relatively young age. In the present paper we report on the development of a functional assay for plasma protein C. In this assay protein C is adsorbed to Al(OH)3, eluted and activated by thrombin, after which the concentration of the activated protein C is measured with a peptide substrate (S2366). Normal values for protein C activity and protein C antigen were determined in healthy volunteers and patients on stable oral anticoagulant treatment. Protein C activity and antigen levels were compared in 28 patients from 9 different pedigrees with both congenital protein C deficiency and thrombotic disease. Two types of protein C deficiency could be recognized: in type I the deficiency is due to the absence or reduced presence of protein C molecules, while in type II the deficiency is caused by the presence of an abnormal protein C molecule with strongly reduced functional activity.
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References
- 1 Kisiel W, Canfield WM, Ericsson LH, Davie EW. Anticoagulant properties of bovine protein C following activation by thrombin. Biochemistry 1977; 16: 5824-5831
- 2 Esmon CT, Comps P, Walker F. Functions for protein C. In: Vitamin K Metabolism and Vitamin K Dependent Proteins. Suttie JW. (ed.) University Park Press; Baltimore: 1980. 1 72-83
- 3 Comp PC, Jacocks RM, Ferrell GL, Esmon CT. Activation of protein C in vivo. J Clin Invest 1982; 70: 127-134
- 4 Mannucci PM, Vigano S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; 2: 463-466
- 5 Stenflo J. A new vitamin K-dependent protein: purification from bovine plasma and preliminary characterization. J Biol Chem 1976; 251: 355-363
- 6 Esmon CT, Stenflo J, Suttie JW. A new vitamin K-dependent protein. A phospholipid binding zymogen of a serine esterase J Biol Chem 1976; 251: 3052-3056
- 7 Owen WG, Esmon CT. Functional properties of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. J Biol Chem 1981; 256: 5532-5535
- 8 Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2249-2252
- 9 Nesheim ME, Canfield WM, Kisiel W, Mann KG. Studies of the capacity of factor X a to protect factor Va from inactivation by activated protein C. J Biol Chem 1982; 257: 1443-1447
- 10 Marlar RA, Kleiss AJ, Griffin JH. Human protein C: inactivation of factor V and VIII in plasma by the activated molecule. Ann NY Acad Sci 1981; 370: 303-310
- 11 Griffin JH, Evatt B, Zimmermann TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-1373
- 12 Bertina RM, Broekmans AW, Van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemostas 1982; 48: 1-5
- 13 Broekmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thrombo-embolism. A study in three Dutch families N Engl J Med 1983; 309: 340-344
- 14 Smith RL. Titration of activated bovine factor X. J Biol Chem 1973; 248: 2418-2423
- 15 Bertina RM, Westhoek-Kuipers ME J, Alderkamp GH J. The inhibitor of prothrombin conversion of patients on oral anticoagulant treatment. Thromb Haemostas 1981; 45: 237-241
- 16 Bertina RM, Van der Linden IK. Inhibitor-neutralisation assay and electro-immuno assay of human factor IX (Christmas factor). Clin Chim Acta 1977; 77: 275-286
- 17 Loeliger EA, Lewis SM. Progress in laboratory control of oral anticoagulants. Lancet 1982; 2: 318-320
- 18 Canfield WM, Kisiel W. Evidence of normal functional levels of activated protein C inhibitor in combined factor V/VIII deficiency disease. J Clin Invest 1982; 70: 1260-1272