Protein C Deficiency: Multimedia

References

1. Dahlback B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood. Jul 1 2008;112(1):19-27. [Medline]. [Full Text].

2. Clouse LH, Comp PC. The regulation of hemostasis: the protein C system. N Engl J Med. May 15 1986;314(20):1298-304. [Medline].

3. Walker FJ. Regulation of activated protein C by a new protein. A possible function for bovine protein S. J Biol Chem. Jun 25 1980;255(12):5521-4. [Medline]. [Full Text].

4. Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood. Apr 15 2007;109(8):3161-72. [Medline]. [Full Text].

5. Reitsma PH, Bernardi F, Doig RG, Gandrille S, on behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH. Protein C deficiency: a database of mutations, 1995 update. Thromb Haemost. May 1995;73(5):876-89. [Medline].

6. D'Ursi P, Marino F, Caprera A, et al. ProCMD: a database and 3D web resource for protein C mutants. BMC Bioinformatics. Mar 8 2007;8 suppl 1:S11. [Medline]. [Full Text].

7. Bovill EG, Bauer KA, Dickerman JD, Callas P, West B. The clinical spectrum of heterozygous protein C deficiency in a large New England kindred. Blood. Feb 15 1989;73(3):712-7. [Medline]. [Full Text].

8. Broekmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thromboembolism. A study of three Dutch families. N Engl J Med. Aug 11 1983;309(6):340-4. [Medline].

9. Horellou MH, Conard J, Bertina RM, Samama M. Congenital protein C deficiency and thrombotic disease in nine French families. Br Med J (Clin Res Ed). Nov 10 1984;289(6454):1285-7. [Medline]. [Full Text].

10. Reitsma PH, Poort SR, Allaart CF, Briet E, Bertina RM. The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects. Blood. Aug 15 1991;78(4):890-4. [Medline]. [Full Text].

11. Mustafa S, Mannhalter C, Rintelen C,et al. Clinical features of thrombophilia in families with gene defects in protein C or protein S combined with factor V Leiden. Blood Coagul Fibrinolysis. Jan 1998;9(1):85-9. [Medline].

12. Tait RC, Walker ID, Reitsma PH, et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost. Jan 1995;73(1):87-93. [Medline].

13. Miletich J, Sherman L, Broze G Jr. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med. Oct 15 1987;317(16):991-6. [Medline].

14. Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J. Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism--results of the Spanish Multicentric Study on Thrombophilia (EMET-Study). Thromb Haemost. Mar 1997;77(3):444-51. [Medline].

15. Gladson CL, Scharrer I, Hach V, Beck KH, Griffin JH. The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemost. Feb 25 1988;59(1):18-22. [Medline].

16. Heijboer H, Brandjes DP, Buller HR, Sturk A, ten Cate JW. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis. N Engl J Med. Nov 29 1990;323(22):1512-6. [Medline].

17. Martinelli I, Mannucci PM, De Stefano V, et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood. Oct 1 1998;92(7):2353-8. [Medline]. [Full Text].

18. Koster T, Rosendaal FR, Briet E, et al. Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia Study). Blood. May 15 1995;85(10):2756-61. [Medline]. [Full Text].

19. Pabinger I, Schneider B, for the Gesellschaft fur Thrombose- und Hamostaseforschung (GTH) Study Group on Natural Inhibitors. Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency. A cooperative, retrospective study. Arterioscler Thromb Vasc Biol. Jun 1996;16(6):742-8. [Medline]. [Full Text].

20. de Bruijn SF, Stam J, Koopman MM, Vandenbroucke JP, for the Cerebral Venous Sinus Thrombosis Study Group. Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users and in [correction of who are] carriers of hereditary prothrombotic conditions. BMJ. Feb 21 1998;316(7131):589-92. [Medline]. [Full Text].

21. Momoi A, Komura Y, Kumon I, et al. Mesenteric venous thrombosis in hereditary protein C deficiency with the mutation at Arg169 (CGG-TGG). Intern Med. Jan 2003;42(1):110-6. [Medline]. [Full Text].

22. Wysokinska EM, Wysokinski WE, Brown RD, et al. Thrombophilia differences in cerebral venous sinus and lower extremity deep venous thrombosis. Neurology. Feb 19 2008;70(8):627-33. [Medline].

23. Melissari E, Kakkar VV. Congenital severe protein C deficiency in adults. Br J Haematol. Jun 1989;72(2):222-8. [Medline].

24. McGehee WG, Klotz TA, Epstein DJ, Rapaport SI. Coumarin necrosis associated with hereditary protein C deficiency. Ann Intern Med. Jul 1984;101(1):59-60. [Medline].

25. Bauer KA. Coumarin-induced skin necrosis. Arch Dermatol. Jun 1993;129(6):766-8. [Medline].

26. Faraci PA, Deterling RA Jr, Stein AM, Rheinlander HF, Cleveland RJ. Warfarin induced necrosis of the skin. Surg Gynecol Obstet. May 1978;146(5):695-700. [Medline].

27. Broekmans AW, Teepe RG, van der Meer FJ, Briet E, Bertina RM. Protein C (PC) and coumarin-induced skin necrosis. Thromb Res. 1986;41(suppl 1):137.

28. Teepe RG, Broekmans AW, Vermeer BJ, Nienhuis AM, Loeliger EA. Recurrent coumarin-induced skin necrosis in a patient with an acquired functional protein C deficiency. Arch Dermatol. Dec 1986;122(12):1408-12. [Medline].

29. Sallah S, Abdallah JM, Gagnon GA. Recurrent warfarin-induced skin necrosis in kindreds with protein S deficiency. Haemostasis. Jan-Feb 1998;28(1):25-30. [Medline].

30. Preston FE, Rosendaal FR, Walker ID, et al. Increased fetal loss in women with heritable thrombophilia. Lancet. Oct 5 1996;348(9032):913-6. [Medline].

31. Vossen CY, Preston FE, Conard J, et al. Hereditary thrombophilia and fetal loss: a prospective follow-up study. J Thromb Haemost. Apr 2004;2(4):592-6. [Medline]. [Full Text].

32. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. Mar 15 2003;361(9361):901-8. [Medline].

33. Kohler J, Kasper J, Witt I, von Reutern GM. Ischemic stroke due to protein C deficiency. Stroke. Jul 1990;21(7):1077-80. [Medline]. [Full Text].

34. Camerlingo M, Finazzi G, Casto L, et al. Inherited protein C deficiency and nonhemorrhagic arterial stroke in young adults. Neurology. Sep 1991;41(9):1371-3. [Medline].

35. Peterman MA, Roberts WC. Syndrome of protein C deficiency and anterior wall acute myocardial infarction at a young age from a single coronary occlusion with otherwise normal coronary arteries. Am J Cardiol. Sep 15 2003;92(6):768-70. [Medline].

36. Douay X, Lucas C, Caron C, Goudemand J, Leys D. Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke. Acta Neurol Scand. Aug 1998;98(2):124-7. [Medline].

37. Munts AG, van Genderen PJ, Dippel DW, van Kooten F, Koudstaal PJ. Coagulation disorders in young adults with acute cerebral ischaemia. J Neurol. Jan 1998;245(1):21-5. [Medline].

38. Boekholdt SM, Kramer MH. Arterial thrombosis and the role of thrombophilia. Semin Thromb Hemost. Sep 2007;33(6):588-96. [Medline].

39. Seligsohn U, Berger A, Abend M, et al. Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med. Mar 1 1984;310(9):559-62. [Medline].

40. Peters C, Casella JF, Marlar RA, Montgomery RR, Zinkham WH. Homozygous protein C deficiency: observations on the nature of the molecular abnormality and the effectiveness of warfarin therapy. Pediatrics. Feb 1988;81(2):272-6. [Medline].

41. Marciniak E, Wilson HD, Marlar RA. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood. Jan 1985;65(1):15-20. [Medline]. [Full Text].

42. Patel RK, Ford E, Thumpston J, Arya R. Risk factors for venous thrombosis in the black population. Thromb Haemost. Nov 2003;90(5):835-8. [Medline].

43. Sakata T, Kario K, Katayama Y, et al. Studies on congenital protein C deficiency in Japanese: prevalence, genetic analysis, and relevance to the onset of arterial occlusive diseases. Semin Thromb Hemost. 2000;26(1):11-6. [Medline].

44. Nardi M, Karpatkin M. Prothrombin and protein C in early childhood: normal adult levels are not achieved until the fourth year of life. J Pediatr. Nov 1986;109(5):843-5. [Medline].

45. van Teunenbroek A, Peters M, Sturk A, Borm JJ, Breederveld C. Protein C activity and antigen levels in childhood. Eur J Pediatr. Aug 1990;149(11):774-8. [Medline].

46. Lensen RP, Rosendaal FR, Koster T, et al. Apparent different thrombotic tendency in patients with factor V Leiden and protein C deficiency due to selection of patients. Blood. Dec 1 1996;88(11):4205-8. [Medline]. [Full Text].

47. Mitchell CA, Rowell JA, Hau L, Young JP, Salem HH. A fatal thrombotic disorder associated with an acquired inhibitor of protein C. N Engl J Med. Dec 24 1987;317(26):1638-42. [Medline].

48. Gordon B, Haire W, Ruby E, et al. Prolonged deficiency of protein C following hematopoietic stem cell transplantation. Bone Marrow Transplant. Mar 1996;17(3):415-9. [Medline].

49. Gerson WT, Dickerman JD, Bovill EG, Golden E. Severe acquired protein C deficiency in purpura fulminans associated with disseminated intravascular coagulation: treatment with protein C concentrate. Pediatrics. Feb 1993;91(2):418-22. [Medline].

50. Michiels JJ, Hamulyak K. Laboratory diagnosis of hereditary thrombophilia. Semin Thromb Hemost. 1998;24(4):309-20. [Medline].

51. Dolan G, Neal K, Cooper P, Brown P, Preston FE. Protein C, antithrombin III and plasminogen: effect of age, sex and blood group. Br J Haematol. Apr 1994;86(4):798-803. [Medline].

52. Martinoli JL, Stocker K. Fast functional protein C assay using Protac, a novel protein C activator. Thromb Res. Aug 1 1986;43(3):253-64. [Medline].

53. Jones DW, Mackie IJ, Winter M, Gallimore M, Machin SJ. Detection of protein C deficiency during oral anticoagulant therapy--use of the protein C:factor VII ratio. Blood Coagul Fibrinolysis. Jun 1991;2(3):407-11. [Medline].

54. Linn YC, Tien SL. Detection of protein C or protein S deficiency in patients on warfarin therapy--a study of nine patients. Ann Acad Med Singapore. Sep 1994;23(5):775-80. [Medline].

55. Schramm W, Spannagl M, Bauer KA, et al. Treatment of coumarin-induced skin necrosis with a monoclonal antibody purified protein C concentrate. Arch Dermatol. Jun 1993;129(6):753-6. [Medline].

56. Dreyfus M, Magny JF, Bridey F, et al. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med. Nov 28 1991;325(22):1565-8. [Medline].

57. Conard J, Bauer KA, Gruber A, et al. Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency. Blood. Aug 15 1993;82(4):1159-64. [Medline]. [Full Text].

58. Dreyfus M, Ladouzi A, Chambost H, et al, for the PROTEXEL Study Group. Treatment of inherited protein C deficiency by replacement therapy with the French purified plasma-derived protein C concentrate (PROTEXEL). Vox Sang. Oct 2007;93(3):233-40. [Medline].

59. Hartman KR, Manco-Johnson M, Rawlings JS, Bower DJ, Marlar RA. Homozygous protein C deficiency: early treatment with warfarin. Am J Pediatr Hematol Oncol. Winter 1989;11(4):395-401. [Medline].

60. Minford AM, Parapia LA, Stainforth C, Lee D. Treatment of homozygous protein C deficiency with subcutaneous protein C concentrate. Br J Haematol. Apr 1996;93(1):215-6. [Medline].

61. [Best Evidence] Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. Mar 3 2009;150(5):293-300. [Medline].

62. [Best Evidence] Klein TE, Altman RB, Eriksson N, et al, for the International Warfarin Pharmacogenetics Consortium. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. Feb 19 2009;360(8):753-64. [Medline].

Further Reading

Related eMedicine Topics

• Antithrombin Deficiency
• Cerebral Venous Thrombosis [in the Neurology section]
• Deep Venous Thrombosis and Thrombophlebitis [in the Emergency Medicine section]
• Dysfibrinogenemia  
• Hypercoagulability: Hereditary Thrombophilia and Lupus Anticoagulants Associated With Venous Thrombosis and Emboli
• Mesenteric Venous Thrombosis [in the General Surgery section]
• Miscarriages Caused by Blood Coagulation Protein or Platelet Deficits
• Protein S Deficiency
• Pulmonary Embolism [in the Emergency Medicine section]

• Activated Protein C and Corticosteroids for Human Septic Shock
• Activated Protein C in Acute Stroke Trial
• Evaluate Protein C levels in Severe Sepsis Patients on Drotrecogin Alfa (Activated)

• Guideline on the assessment of bleeding risk prior to surgery or invasive procedures. British Committee for Standards in Haematology - Professional Association. 2007. 25 pages. NGC:006183
• Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. British Committee for Standards in Haematology - Professional Association. 2004 Jul. 18 pages. NGC:006191
• Prevention of deep vein thrombosis and pulmonary embolism. American College of Obstetricians and Gynecologists - Medical Specialty Society. 2000 Oct (revised 2007 Aug). 12 pages. NGC:005947
• Venous thromboembolism. Institute for Clinical Systems Improvement - Private Nonprofit Organization. 1998 Jun (revised 2007 Jun). 91 pages. [NGC Update Pending] NGC:005885
• Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). American College of Chest Physicians - Medical Specialty Society. 2001 Jan (revised 2008 Jun). 43 pages. NGC:006675

Keywords

protein C deficiency, thrombophilia, hypercoagulability, venous thromboembolism, VTE, acquired protein C deficiency, warfarin-induced skin necrosis, WISN, neonatal purpura fulminans, NPF, activated protein C resistance, aPC, inherited blood coagulation disorders, inherited blood protein disorders

Contributor Information and Disclosures

Author

Adam Cuker, MD, Fellowship in Hematology/Oncology, Hospital of the University of Pennsylvania
Adam Cuker, MD is a member of the following medical societies: American Society of Hematology, Hemophilia and Thrombosis Research Society, International Society on Thrombosis and Haemostasis, and National Hemophilia Foundation
Disclosure: Nothing to disclose.

Coauthor(s)

Eleanor S Pollak, MD, Associate Director of Special Coagulation, Associate Professor, Department of Pathology and Laboratory Medicine, Section of Hematology and Coagulation, University of Pennsylvania
Eleanor S Pollak, MD is a member of the following medical societies: American Society of Hematology, College of American Pathologists, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

Medical Editor

David Aboulafia, MD, Medical Director, Bailey-Boushay House; Clinical Professor, Department of Medicine, Division of Hematology, University of Washington
David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.