Protein S Deficiency Treatment & Management

  • Author: John E Godwin, MD, MS; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

Medical Care

Management of protein S deficiency takes place in the event of acute VTE or in patients with asymptomatic carrier states without a thrombotic event. Following an acute thrombosis, administer heparin therapy and then transition to warfarin oral anticoagulation.

  • Heparin therapy
    • Physicians may administer the initial heparin treatment as intravenous unfractionated heparin or as subcutaneous low molecular weight heparin (LMWH).
    • Heparin should be administered for a minimum of 5 days.
    • Manage heparin with standard protocols. See Deep Venous Thrombosis or Pulmonary Embolism for additional details.
  • Warfarin
    • Warfarin administration can start on day 1 or 2 of heparin therapy. After 2 consecutive therapeutic international normalized ratio (INR) clotting tests and a minimum of 5 days of heparin therapy, the patient can continue on warfarin alone.
    • In most patients, specialists recommend 6-9 months of initial treatment with warfarin.
    • The question of whether to continue lifelong warfarin in patients with identified protein S deficiency after their first thrombotic event is controversial. If the first thrombotic event was life threatening or occurred in multiple or unusual sites (eg, cerebral veins, mesenteric veins), most experts recommend lifelong therapy initially. If precipitated by a strong event (eg, trauma, surgery) and the thrombosis did not meet the criteria of life threatening or multiple or unusual sites, some experts argue that these patients may have a lower risk of recurrence and deserve a trial without warfarin after 9 months.
  • In patients who are asymptomatic carriers of protein S deficiency, the goal of therapy is prevention of the first thrombosis. In such patients, avoid drugs that predispose to thrombosis, including oral contraceptives. In these patients, if surgery or orthopedic injury occurs, prophylaxis with heparin is mandatory.
  • In pregnancy, experts recommend prophylaxis with heparin; however, the timing is controversial. Most experts would treat from the second trimester through 4-6 weeks postpartum.
  • Patient bleeding risks must be assessed on an individual basis for any of these prophylactic recommendations, and no single prescription fits all cases.
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Diet

Dietary issues relate to patients with protein S deficiency who are on oral anticoagulation with warfarin. Avoid diets rich in vitamin K foods.

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Activity

Restrictions apply to activity shortly after acute venous thrombosis (ie, DVT, pulmonary embolism). See Deep Venous Thrombosis or Pulmonary Embolism for additional details concerning such restrictions. While on anticoagulation therapy, patients should avoid vigorous contact activities.

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Contributor Information and Disclosures
Author

John E Godwin, MD, MS  Professor of Medicine, Chief Division of Hematology/Oncology, Associate Director, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine

John E Godwin, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Rodger L Bick†, MD, PhD, FACP  Former Clinical Professor of Medicine, University of Texas Southwestern Medical Center; Former Director, Dallas and Pacific Thrombosis Hemostasis and Vascular Medicine Clinical Center

Rodger L Bick†, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American Cancer Society, American College of Angiology, American College of Physicians, American Geriatrics Society, American Heart Association, American Medical Association, American Society for Clinical Pathology, American Society of Hematology, Association of Clinical Scientists, California Medical Association, California Thoracic Society, International College of Angiology, International Society of Hematology, International Society on Thrombosis and Haemostasis, New York Academy of Sciences, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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.

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, Jefferson Medical College of 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 Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Castoldi E, Hackeng TM. Regulation of coagulation by protein S. Curr Opin Hematol. Sep 2008;15(5):529-36. [Medline].

  2. Soare AM, Popa C. Deficiencies of proteins C, S and antithrombin and activated protein C resistance--their involvement in the occurrence of Arterial thromboses. J Med Life. Oct-Dec 2010;3(4):412-5. [Medline]. [Full Text].

  3. Castoldi E, Maurissen LF, Tormene D, Spiezia L, Gavasso S, Radu C, et al. Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from families with mixed type I/III protein S deficiency. Haematologica. Sep 2010;95(9):1563-71. [Medline]. [Full Text].

  4. Marlar RA, Gausman JN. Protein S abnormalities: a diagnostic nightmare. Am J Hematol. May 2011;86(5):418-21. [Medline].

  5. Heeb MJ, Prashun D, Griffin JH, Bouma BN. Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor. FASEB J. Jul 2009;23(7):2244-53. [Medline].

  6. Lijfering WM, Brouwer JL, Veeger NJ, Bank I, Coppens M, Middeldorp S, et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood. May 21 2009;113(21):5314-22. [Medline].

  7. Brouwer JL, Lijfering WM, Ten Kate MK, Kluin-Nelemans HC, Veeger NJ, van der Meer J. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin. Thromb Haemost. Jan 2009;101(1):93-9. [Medline].

  8. Edlich RF, Cross CL, Dahlstrom JJ, Long WB 3rd. Modern concepts of the diagnosis and treatment of purpura fulminans. J Environ Pathol Toxicol Oncol. 2008;27(3):191-6. [Medline].

  9. Alvi AR, Khan S, Niazi SK, Ghulam M, Bibi S. Acute mesenteric venous thrombosis: improved outcome with early diagnosis and prompt anticoagulation therapy. Int J Surg. Jun 2009;7(3):210-3. [Medline].

  10. Tripodi A, Asti D, Chantarangkul V, Biguzzi E, Mannucci PM. Interference of factor V Leiden on protein S activity: evaluation of a new prothrombin time-based assay. Blood Coagul Fibrinolysis. Sep 2007;18(6):543-6. [Medline].

  11. Adachi T. Protein S and congenital protein S deficiency: the most frequent congenital thrombophilia in Japanese. Curr Drug Targets. Aug 2005;6(5):585-92. [Medline].

  12. Baker ME, French FS, Joseph DR. Vitamin K-dependent protein S is similar to rat androgen-binding protein. Biochem J. Apr 1 1987;243(1):293-6. [Medline].

  13. Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med. Jul 15 1993;119(2):104-9. [Medline].

  14. Dahlback B, Villoutreix BO. The anticoagulant protein C pathway. FEBS Lett. Jun 13 2005;579(15):3310-6. [Medline].

  15. Dahlbäck B, Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc Natl Acad Sci U S A. Apr 1981;78(4):2512-6. [Medline].

  16. Di Scipio RG, Hermodson MA, Yates SG, Davie EW. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S. Biochemistry. Feb 22 1977;16(4):698-706. [Medline].

  17. Francis RB Jr. Protein S deficiency in sickle cell anemia. J Lab Clin Med. May 1988;111(5):571-6. [Medline].

  18. Giri TK, Villoutreix BO, Wallqvist A, Dahlbäck B, de Frutos PG. Topological studies of the amino terminal modules of vitamin K-dependent protein S using monoclonal antibody epitope mapping and molecular modeling. Thromb Haemost. Nov 1998;80(5):798-804. [Medline].

  19. Gomez E, Poort SR, Bertina RM, Reitsma PH. Identification of eight point mutations in protein S deficiency type I--analysis of 15 pedigrees. Thromb Haemost. May 1995;73(5):750-5. [Medline].

  20. Hackeng TM, Rosing J. Protein S as cofactor for TFPI. Arterioscler Thromb Vasc Biol. Aug 6 2009;epub ahead of print. [Medline].

  21. Hackeng TM, van 't Veer C, Meijers JC, Bouma BN. Human protein S inhibits prothrombinase complex activity on endothelial cells and platelets via direct interactions with factors Va and Xa. J Biol Chem. Aug 19 1994;269(33):21051-8. [Medline].

  22. Heeb MJ, Rosing J, Bakker HM, Fernandez JA, Tans G, Griffin JH. Protein S binds to and inhibits factor Xa. Proc Natl Acad Sci U S A. Mar 29 1994;91(7):2728-32. [Medline].

  23. Hillarp A, Dahlback B. Novel subunit in C4b-binding protein required for protein S binding. J Biol Chem. Sep 5 1988;263(25):12759-64. [Medline].

  24. Ploos van Amstel HK, Huisman MV, Reitsma PH, Wouter ten Cate J, Bertina RM. Partial protein S gene deletion in a family with hereditary thrombophilia. Blood. Feb 1989;73(2):479-83. [Medline].

  25. Ploos van Amstel HK, Reitsma PH, van der Logt CP, Bertina RM. Intron-exon organization of the active human protein S gene PS alpha and its pseudogene PS beta: duplication and silencing during primate evolution. Biochemistry. Aug 28 1990;29(34):7853-61. [Medline].

  26. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med. Apr 6 1995;332(14):912-7. [Medline].

  27. Schmidel DK, Nelson RM, Broxson EH Jr, Comp PC, Marlar RA, Long GL. A 5.3-kb deletion including exon XIII of the protein S alpha gene occurs in two protein S-deficient families. Blood. Feb 1 1991;77(3):551-9. [Medline].

  28. Schmidel DK, Tatro AV, Phelps LG, Tomczak JA, Long GL. Organization of the human protein S genes. Biochemistry. Aug 28 1990;29(34):7845-52. [Medline].

  29. Siddique RM, Siddique MI, Connors AF Jr, Rimm AA. Thirty-day case-fatality rates for pulmonary embolism in the elderly. Arch Intern Med. Nov 11 1996;156(20):2343-7. [Medline].

  30. Simmonds RE, Zöller B, Ireland H, Thompson E, de Frutos PG, Dahlbäck B, et al. Genetic and phenotypic analysis of a large (122-member) protein S-deficient kindred provides an explanation for the familial coexistence of type I and type III plasma phenotypes. Blood. Jun 15 1997;89(12):4364-70. [Medline].

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

  32. Walker MC, Garner PR, Keely EJ, Rock GA, Reis MD. Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol. Jul 1997;177(1):162-9. [Medline].

  33. Watkins PC, Eddy R, Fukushima Y, Byers MG, Cohen EH, Dackowski WR, et al. The gene for protein S maps near the centromere of human chromosome 3. Blood. Jan 1988;71(1):238-41. [Medline].

  34. Zhang D, Hao J, Yang N. Protein C and D-dimer are related to portal vein thrombosis in patients with liver cirrhosis. J Gastroenterol Hepatol. Aug 3 2009;epub ahead of print. [Medline].

 
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A simplified outline of the protein C system.
 
 
 
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