Skip to main content
SpringerLink
Log in

Clinical relevance of protein C

  • Review Article
  • Published:
Blut Aims and scope Submit manuscript

Summary

Protein C is, after activation by thrombin, a potent inhibitor of blood coagulation. An isolated deficiency of protein C increases the risk of thrombosis. The two forms of protein C deficiency, the heterozygous and the homozygous deficiency state, have different clinical features. Patients with heterozygous protein C deficiency are at a high risk to develop venous thrombosis and pulmonary embolism. In newborns with homozygous protein C deficiency with very low protein C levels (1%) a purpura fulminans like syndrome was observed. Heparin and coumarin derivatives are effective drugs in heterozygous protein C deficiency, homozygous patients may be treated either by replacement of protein C or coumarin derivatives. Decreased protein C levels were observed in various other diseases: Chronic and acute liver disease, disseminated intravascular coagulation, malignancy, postoperatively and during treatment with asparaginase. The role of protein C in these diseases to trigger thrombosis is not yet established.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barbui T, Rodeghiero F, Meli S, Dini E (1983) Fatal pulmonary embolism and antithrombin III deficiency in adult lymphoblastic leukemia durin L-Asparaginase therapy. Acta Haematol 69: 188–191

    Google Scholar 

  2. Barbui T, Finazzi G, Vigano S, Mannucci PM (1984) L-Asparaginase lowers protein C antigen. Thromb Haemost 52: 216

    Google Scholar 

  3. Bertina RM, Broekmans AW, Van der Linden IK, Mertens K (1982) Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 48: 1–5

    Google Scholar 

  4. Bertina RM, Broekmans AW (1982) Protein C concentrates for therapeutic use. Lancet II: 1384

    Google Scholar 

  5. Bertina RM, Broekmans AW, van Es-Krommenhoek C, van Wijngaarden A (1984) The use of functional and immunological assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. Thromb Haemost 51: 1–5

    Google Scholar 

  6. Boyer C, Rothschild CM, Wolf M, Amiral J, Meyer D, Larrieu MJ (1984) A new method for the estimation of protein C by ELISA. Thromb Res 36: 579–589

    Google Scholar 

  7. Branson HE, Katz J, Marble R, Griffin JM (1983) Inherited protein C deficiency and coumarin responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 2: 1165–1168

    Google Scholar 

  8. Broekmans AW, Bertina RM, Loeliger EA, Hofman V, Klingemann HG (1983) Protein C and the development of skin necrosis during anticoagulant therapy. Thromb Haemost 49: 244

    Google Scholar 

  9. Broekmans AW, Veltkamp JJ, Bertina RM (1983) Congenital protein C deficiency and venous thromboembolism. A study in three Dutch families. N Engl J Med 309: 340–344

    Google Scholar 

  10. Broekmans AW, van der Linden IK, Veltkamp JJ, Bertina RM (1983) Prevalence of isolated protein C deficiency in patients with venous thrombotic disease and in the population. Thromb Haemost 50: 350

    Google Scholar 

  11. Broekmans AW, Bertina RM, Reinalda-Poot J, Engesser L, Muller HP, Leeuw JA, Michiels JJ, Brommer EJP, Briet E (1985) Hereditary protein S deficiency and venous thromboembolism. Thromb Haemost 53: 273–277

    Google Scholar 

  12. Broekmans AW, Conard J, Weyenberg RG, Horellou M (1985) Treatment of hereditary protein C (PC) deficiency with stanazolol. Thromb Haemost 54: 142

    Google Scholar 

  13. Broekmans AW, Bertina RM (1985) Protein C. In: Recent advances in blood coagulation. Churchill, Livingstone Edinburgh London Melbourne New York pp 117–135

    Google Scholar 

  14. Comp PC, Esmon CT (1978) Initiation of clot lysis in plasma by activated protein C. Circulation (Suppl II) 57/58: 210

    Google Scholar 

  15. Comp PC, Esmon CT (1981) Generation of fibrinolytic activity by infusion of activated protein C in dogs. J Clin Invest 68: 1221-≃1228

    Google Scholar 

  16. Comp PC, Esmon CT (1984) Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 311: 1525–1528

    Google Scholar 

  17. Comp PC, Nixon RR, Esmon CT (1984) Determination of functional levels of protein C, an antithrombotic protein, using thrombin-thrombomodulin complex. Blood 63: 15–21

    Google Scholar 

  18. Crabtree GR, Plutzky J, Marlar R, Bertina RM, Broekmans AW, Griffin J, Zarcharski L, Gruppo R, Sala N, Long G (1985) The range of genotypes underlying human protein C deficiency. Thromb Haemost 54: 56

    Google Scholar 

  19. Dahlbäck B, Stenflo J (1980) Inhibitory effect of activated protein C on activation of prothrombin by plateletbound cofactor Xa. Eur J Biochem 107: 331–335

    Google Scholar 

  20. D'Angelo A, Comp PC, Tripodi A, Ponticelli C, Vigano S (1985) Identification of a new type of protein C abnormality with decreased anticoagulant activity. Thromb Haemost 54: 107

    Google Scholar 

  21. Epstein DJ, Bergum PW, Rapaport SI (1983) Kinetics of protein C depression after coumadin administration. Circulation (Suppl III) 68: 316

    Google Scholar 

  22. Esmon CT, Owen WG (1981) Identification of an endothelial cell cofactor for thrombin catalized activation of protein C. Proc Natl Acad Sci USA 78: 2245–225

    Google Scholar 

  23. Esmon CT, Esmon NL, Harris KW (1982) Complex formation between thrombomodulin inhibits both thrombin-catalyzed fibrin formation and F V activation. J Biol Chem 257: 7944–7947

    Google Scholar 

  24. Esmon NL, Roger CC, Esmon CT (1983) Thrombomodulin blocks the ability of thrombin to activate platelets. J Biol Chem 258: 1238–1242

    Google Scholar 

  25. Estelles A, Garcia-Plaza I, Dasi A, Aznar J, Duart M, Sanz G, Perez-Requejo JL, Espana F, Jimenez C, Abeledo G (1984) Severe inherited “homozygous” protein C deficiency in a newborn infant. Thromb Haemost 52: 53–56

    Google Scholar 

  26. Fletcher BT, Lockhart MS (1985) A new function for activated protein C: Activated protein C prevents inhibition of plasminogen activators by release from mononuclear leukocytes-platelet suspensions stimulated by phorbol diester. Thromb Res 37: 155–164

    Google Scholar 

  27. Fletcher BT, Lockhart MS (1985) Whole blood clot lysis: In vitro modulation by activated protein C. Thromb Res 37: 639–649

    Google Scholar 

  28. Foster DC, Yositake S, Davie EW (1985) Characterization of the gene for human protein C. Thromb Haemost 54: 55

    Google Scholar 

  29. Francis RB, Patch MJ (1983) A functional assay for protein C in human plasma. Thromb Res 32: 605–613

    Google Scholar 

  30. Francis RB, Wood RD, Patch MJ, McGehee WG (1985) Reduced functional protein C levels in massive obesity. Thromb Haemost 54: 37

    Google Scholar 

  31. Fulcher CA, Gardiner EJ, Griffin JH, Zimmermann TS (1984) Proteolytic inactivation of human F VIII procoagulant protein by activated protein C and its analogy with F V. Blood 63: 486–489

    Google Scholar 

  32. Griffin JH, Evatt B, Zimmermann TS, Kleiss AJ, Wideman C (1981) Deficiency of protein C in congenital thrombotic disease. J Clin Invest 68: 1370–1373

    Google Scholar 

  33. Griffin JH, Mosher DF, Zimmermann TS, Kleiss AJ (1982) Protein C, an antithrombotic protein, is reduced in hospitalized patients with intravascular coagulation. Blood 60: 261–264

    Google Scholar 

  34. Hofmann V, Frick PG (1982) Repeated occurrence of skin nekrosis twice following coumarin intake and subsequently during decrease of vitamin K dependent coagulation factors associated with cholestasis. Thromb Haemost 48: 245–246

    Google Scholar 

  35. Horellou MH, Conard J, Bertina RM, Samama M (1984) Congenital protein C deficiency and thrombotic disease in nine French families. Brit Med J 289: 1285–1287

    Google Scholar 

  36. Kisiel W, Canfield WM, Ericson LH, Davie EW (1977) Anticoagulant properties of bovine plasma protein C following activation by thrombin. Biochem 16: 5824–5830

    Google Scholar 

  37. Kisiel W (1979) Human protein C: Isolation, characterization and mechanism of activation by a-thrombin. J Clin Invest 64: 761–769

    Google Scholar 

  38. Loeliger EA, Broekmans AW (1984) Drugs affecting blood clotting and fibrinolysis. In: Meyler's side effect of drugs. 659–661

  39. Long GL, Bang NU, Beckmann RJ, Hoskins GA, Jaskunas SR, Little SP, Santerre RF, Crabtree GR (1985) Cloning, DNA sequencing, and expression of genetic material coding for human protein C. Thromb Haemost 54: 56

    Google Scholar 

  40. Mammen JF, Thomas WR, Seegers WH (1960) Activation of purified prothrombin to autoprothrombin II-A. Thromb Diath Haemorrh 5: 218–250

    Google Scholar 

  41. Mannucci PM, Vigano S (1982) Deficiencies of protein C, an inhibitor of blood coagulation. Lancet II: 463–466

    Google Scholar 

  42. Mannucci PM, Vigano S (1983) Protein C concentrates for therapeutic use. Lancet I: 875

    Google Scholar 

  43. Mannucci PM, Bottasso B, Sharon C, Tripodi A (1984) Treatment with Stanazolol of type I protein C deficiency in an Italian family. Ricera Clin Lab 14: 673–679

    Google Scholar 

  44. Mannucci PM, Vigano S, Bottasso B, Candotti G, Bozetti P, Rossi E, Pardi G (1984) Protein C: Antigen during pregnancy, delivery and puerperium. Thromb Haemost 52: 217

    Google Scholar 

  45. Marcinak E, Wilson HD, Marlar RA (1985) Neonatal purpura fulminans: A genetic disorder related to the absence of protein C in blood. Blood 65: 15–20

    Google Scholar 

  46. Marlar RA, Kleiss AJ, Griffin JH (1982) Mechanism of action of activated protein C, a thrombin dependent anticoagulant enzyme. Blood 59: 1062–1072

    Google Scholar 

  47. Marlar RA, Endres-Brooks J, Miller C (1985) Serial studies of protein C and its plasma inhibitor in patients with disseminated intravascular coagulation. Blood 66: 59–63

    Google Scholar 

  48. McGehee WG, Klotz TA, Epstein DJ, Rapaport SI (1984) Coumarin necrosis associated with hereditary protein C deficiency. Ann Intern Med 100: 59–60

    Google Scholar 

  49. Oehler G, Matthes K (1985) Protein C in various liver diseases. In: Protein C — Biochemical and medical aspects, de Gruyter Berlin New York pp 135–140

    Google Scholar 

  50. Pabinger-Fasching I, Bertina RM, Lechner K, Niessner H, Korninger C (1983) Protein C deficiency in two Austrian families. Thromb Haemost 50: 810–813

    Google Scholar 

  51. Pabinger-Fasching I, Lechner K (1984) Protein-C-Mangel und Thromboseneigung. Folia Haematol 4: 416–420

    Google Scholar 

  52. Pabinger I (1985) Protein C Mangel. Hämostaseologie 5: 134–138

    Google Scholar 

  53. Pabinger-Fasching I, Lechner K, Niessner H, Schmidt P, Balzar E, Mannhalter C (1985) High levels of plasma protein C in nephrotic syndrome. Thromb Haemost 53: 5–7

    Google Scholar 

  54. Pabinger-Fasching I, Stoffels U, Lechner K (1985) Protein C determination in patients with thrombotic diseases and disseminated intravascular coagulation. In: Protein C — Biochemical and medical aspects, de Gruyter Berlin New York pp 141–150

    Google Scholar 

  55. Pabinger-Fasching I, Deutsch E (1985) Protein C deficiency in Austria. Semin Thromb Hemost 11: 347–351

    Google Scholar 

  56. Polack B, Pouzol P, Amiral J, Kolodie L (1984) Protein C level at birth. Thromb Haemost 52: 188–190

    Google Scholar 

  57. Rodeghiero F, Mannucci PM, Vigano S, Barbui T, Gugliotta L, Cortellaro M, Dini E (1984) Liver dysfunction rather than intravascular coagulation as a main cause of low protein C and antithrombin III in acute leukemia. Blood 63: 965–969

    Google Scholar 

  58. Rose VL, Fareed J, Kwaan HC (1985) Protein C: Ag deficiency and coumadin necrosis. Thromb Haemost 54: 144

    Google Scholar 

  59. Sala N, Owen WG, Collen D (1984) A functional assay of protein C in human plasma. Blood 63: 671–675

    Google Scholar 

  60. Sala N, Borrell M, Fontcuberta J, Felez J, Rutlant ML (1985) Qualitative defect of protein C in a patient with recurrent venous thrombosis. Thromb Haemost 54: 142

    Google Scholar 

  61. Samama M, Horellou MH, Soria J, Conard J, Nicolas G (1984) Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Thromb Haemost 51: 132–133

    Google Scholar 

  62. Schöndorf TH, Witt J (1985) Protein C in patients under L-Asparaginase treatment. In: Protein C — Biochemical and medical aspects, de Gruyter Berlin New York pp 125–134

    Google Scholar 

  63. Schwarz HP, Fischer M, Hoppmeier P, Batard MA, Griffin JH (1984) Plasma protein S deficiency in familial thrombotic disease. Blood 64: 1297–1300

    Google Scholar 

  64. Seegers WH, Novoa E, Henry RL, Hassouna HI (1976) Relationship of “new” vitamin K dependent protein C and “old” autoprothrombin II-A. Thromb Res 8: 543–552

    Google Scholar 

  65. Seegers WH, McCoy EL, Groben HD, Sakuragawa N, Agrawal BBL (1972) Purification and some properties of autoprothrombin II-A: An anticoagulant perhaps also related to fibrinolysis. Thromb Res 1: 443–460

    Google Scholar 

  66. Seligsohn U, Berger A, Abend M, Rubin L, Attias D, Zivelin A, Rapaport SI (1984) Homozygous protein C deficiency manifested by massive venous thrombosis in a newborn. N Engl J Med 310: 559–562

    Google Scholar 

  67. Stills RH, Marlara RA, Montgomery RR, Deshpande GN, Humbert JR (1984) Severe homozygous protein C deficiency. J Pediatr 105: 409–413

    Google Scholar 

  68. Spicer TE, Rau MC (1976) Purpura fulminans. Am J Med 61: 566–571

    Google Scholar 

  69. Stenflo J (1976) A new vitamin K dependent protein. J Biol Chem 251: 355–363

    Google Scholar 

  70. Stenflo J (1984) Structure and function of protein C. Sem Thromb Haemost 10: 109–121

    Google Scholar 

  71. Suzuki K, Stenflo J, Dahlbäck B, Teodorsson B (1983) Inactivation of human coagulation factor V by activated protein C. J Biol Chem 258: 1914–1920

    Google Scholar 

  72. Suzuki K (1984) Activated protein C inhibitor. Sem Thromb Haemost 10: 154–161

    Google Scholar 

  73. Thaler E, Lechner K (1981) Antithrombin III deficiency and thromboembolism. Clin Haematol 10: 369–390

    Google Scholar 

  74. Vikydal R, Korninger C, Kyrle PA, Niessner H, Pabinger I, Thaler E, Lechner K (1985) The prevalence of hereditary antithrombin III-deficiency in patients with a history of venous thromboembolism. Thromb Haemost 54: 744–745

    Google Scholar 

  75. Vigano S, Mannucci PM, Solinas S, Bottasso B, Mariani G (1984) Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Brit J Haematol 57: 213–220

    Google Scholar 

  76. Vigano S, D'Angelo A, Comp PC, Esmon CT (1985) A new functional assay for protein C assessment of protein C activity during oral anticoagulation. Thromb Haemost 54: 107

    Google Scholar 

  77. Walker FJ (1980) Regulation of activated protein C by a new protein. A possible function for bovine protein S. J Biol Chem 255: 5521–5524

    Google Scholar 

  78. Wehinger H, Witt J (1985) Protein C deficiency in a newborn infant with purpura fulminans. In: Protein C — Biochemical and medical aspects, de Gruyter Berlin New York pp 117–124

    Google Scholar 

  79. Wintzen AR, Broekmans AW, Bertina RM, Briet E, Zecha A, Vielvoye J, Bots GTAM (1985) Cerebral hemorrhagic infarction in young patients with hereditary protein C deficiency: evidence for “spontaneous” cerebral venous thrombosis. Brit Med J 290: 350–352

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Internal Medicine, University of Vienna, Lazarettgasse 14, A-1090, Wien, Austria

    I. Pabinger

Authors
  1. I. Pabinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pabinger, I. Clinical relevance of protein C. Blut 53, 63–75 (1986). https://doi.org/10.1007/BF00321089

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00321089

Key words

Search

Navigation