Abstract
Protein C (PC) is a 62-kDa vitamin K-dependent plasma zymogen which, after activation to serine protease, plays an important role in the physiologic regulation of blood coagulation.
Given that PC is one of the major naturally occurring inhibitors of coagulation, acquired or hereditary deficiencies of this protein result in excessive thrombin generation. As a vast array of mutations are responsible for hereditary PC deficiencies, screening for their presence by DNA testing would require sequencing each entire gene involving numerous exons. Moreover, the knowledge of the gene mutation does not offer any benefit in the treatment of thrombophilic families, so the routine molecular characterization is not indicative. These defects are detected by functional or immunological assays. Measurement of PC activity is essential to identify subjects with both type I and type II PC defects. There is no need to routinely perform PC immunological assays. However, they are useful in order to distinguish type I from type II PC hereditary deficiency.
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References
Kisiel W (1979) Human plasma protein C: isolation, characterization, and mechanism of activation by alpha-thrombin. J Clin Invest 64:761–769
Stenflo J, Fernlund P (1982) Amino acid sequence of the heavy chain of bovine protein C. J Biol Chem 257:12180–12190
Sadler JE (1993) Structure-function-relationships of the thrombin-thrombomodulin interaction. Haemostasis 23:183
Reitsma PH, Bernardi F, Doig RG et al (1995) Protein C deficiency: a database of mutations, 1995 update. On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH. Thromb Haemost 73:876–889
Richards SM, Olson T, Keyes LD (1990) Quantitative and functional assays compared for determination of zymogen and activated human protein C. Clin Chem 36:1892–1896
Amiral J, Adalbert B, Adam M (1984) Application of enzyme immunoassays to coagulation testing. Clin Chem 30:1512–1516
Laurell C (1977) Electroimmunoassay. Scand J Clin Lab Invest 29:21–37
Ikeda K, Stenflo J (1985) A radioimmunoassay for protein C. Thromb Res 39:297–306
Mikami S, Tuddenham EG (1986) Studies on immunological assay of vitamin K dependent factors. II. Comparison of four immunoassay methods with functional activity of protein C in human plasma. Br J Haematol 62:183–193
Andrew M, Paes B, Milner R et al (1987) Development of the human coagulation system in the full-term infant. Blood 70:165–172
Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L (1992) Maturation of the hemostatic system during childhood. Blood 80:1998–2005
Monagle P, Barnes C, Ignjatovic V et al (2006) Developmental haemostasis—impact for clinical haemostasis laboratories. Thromb Haemost 95:362–372
Jennings I, Kitchen S, Woods TA, Preston FE (2005) Multilaboratory testing in thrombophilia through the United Kingdom National External Quality Assessment Scheme (Blood Coagulation) Quality Assurance Program. Semin Thromb Hemost 31:66–72
Pabinger I, Allaart CF, Hermans J, Briet E, Bertina RM (1992) Hereditary protein C-deficiency: laboratory values in transmitters and guidelines for the diagnostic procedure. Report on a study of the SSC Subcommittee on Protein C and Protein S. Protein C Transmitter Study Group. Thromb Haemost 68:470–474
Kottke-Marchant K, Comp P (2002) Laboratory issues in diagnosing abnormalities of protein C, thrombomodulin, and endothelial cell protein C receptor. Arch Pathol Lab Med 126:1337–1348
de Moerloose P, Reber G, Bouvier CA (1988) Spuriously low levels of protein C with a Protac activation clotting assay. Thromb Haemost 59:543
Faioni EM, Franchi F, Asti D, Mannucci PM (1996) Resistance to activated protein C mimicking dysfunctional protein C: diagnostic approach. Blood Coagul Fibrinolysis 7:349–352
Faioni EM, Hermida J, Rovida E et al (2000) Type II protein C deficiency: identification and molecular modelling of two natural mutants with low anticoagulant and normal amidolytic activity. Br J Haematol 108:265–271
Bovill EG, Tomczak JA, Grant B et al (1992) Protein CVermont: symptomatic type II protein C deficiency associated with two GLA domain mutations. Blood 79:1456–1465
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Hepner, M., Karlaftis, V. (2013). Protein C. In: Monagle, P. (eds) Haemostasis. Methods in Molecular Biology, vol 992. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-339-8_29
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DOI: https://doi.org/10.1007/978-1-62703-339-8_29
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