Protein S Deficiency Questions & Answers

1. Piccin A, Murphy C, Eakins E, Kinsella A, McMahon C, Smith OP, et al. Protein C and free protein S in children with sickle cell anemia. Ann Hematol. 2012 Oct. 91 (10):1669-71. [Medline].

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

3. 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. 2010 Oct-Dec. 3(4):412-5. [Medline]. [Full Text].

4. 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. 2010 Sep. 95(9):1563-71. [Medline]. [Full Text].

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

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

7. 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. 1994 Mar 29. 91(7):2728-32. [Medline].

8. Anderson HA, Maylock CA, Williams JA, Paweletz CP, Shu H, Shacter E. Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol. 2003 Jan. 4 (1):87-91. [Medline].

9. 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. 2009 Jul. 23(7):2244-53. [Medline]. [Full Text].

10. 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. 2009 Jan. 101(1):93-9. [Medline].

11. 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].

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

13. Ikejiri M, Wada H, Yamada N, Nakamura M, Fujimoto N, Nakatani K, et al. High prevalence of congenital thrombophilia in patients with pregnancy-related or idiopathic venous thromboembolism/pulmonary embolism. Int J Hematol. 2017 Mar. 105 (3):272-279. [Medline].

14. Fraga R, Diniz LM, Lucas EA, Emerich PS. Warfarin-induced skin necrosis in a patient with protein S deficiency. An Bras Dermatol. 2018 Jul-Aug. 93 (4):612-613. [Medline]. [Full Text].

15. 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. 2009 Jun. 7(3):210-3. [Medline].

16. 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. 1988 Jan. 71(1):238-41. [Medline].

17. 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. 1990 Aug 28. 29(34):7853-61. [Medline].

18. Schmidel DK, Tatro AV, Phelps LG, Tomczak JA, Long GL. Organization of the human protein S genes. Biochemistry. 1990 Aug 28. 29(34):7845-52. [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. 1995 May. 73(5):750-5. [Medline].

20. Jang MA, Kim SH, Kim DK, Kim HJ. A novel nonsense mutation Tyr301* of PROS1 causing protein S deficiency. Blood Coagul Fibrinolysis. 2015 Mar. 26 (2):223-4. [Medline].

21. Huang X, Xu F, Assa CR, Shen L, Chen B, Liu Z. Recurrent pulmonary embolism associated with deep venous thrombosis diagnosed as protein s deficiency owing to a novel mutation in PROS1: A case report. Medicine (Baltimore). 2018 May. 97 (19):e0714. [Medline]. [Full Text].

22. 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. 2009 May 21. 113(21):5314-22. [Medline].

23. 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. 1989 Feb. 73(2):479-83. [Medline].

24. 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. 1991 Feb 1. 77(3):551-9. [Medline].

25. Castoldi E, Simioni P, Tormene D, Rosing J, Hackeng TM. Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma. J Thromb Haemost. 2010 Feb. 8 (2):294-300. [Medline]. [Full Text].

26. Yilmaz S, Gunaydin S. Inherited risk factors in low-risk venous thromboembolism in patients under 45 years. Interact Cardiovasc Thorac Surg. 2014 Oct 17. [Medline].

27. Klostermeier UC, Limperger V, Kenet G, Kurnik K, Alhenc Gelas M, Finckh U, et al. Role of protein S deficiency in children with venous thromboembolism. An observational international cohort study. Thromb Haemost. 2014 Oct 2. 113(1):[Medline].

28. 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. 2007 Sep. 18(6):543-6. [Medline].

29. Alshaikh NA, Rosing J, Thomassen MCLGD, Castoldi E, Simioni P, Hackeng TM. New functional assays to selectively quantify the activated protein C- and tissue factor pathway inhibitor-cofactor activities of protein S in plasma. J Thromb Haemost. 2017 May. 15 (5):950-960. [Medline].

30. Ameku K, Higa M. Rivaroxaban Treatment for Warfarin-Refractory Thrombosis in a Patient with Hereditary Protein S Deficiency. Case Rep Hematol. 2018. 2018:5217301. [Medline]. [Full Text].

Mohammad Muhsin Chisti, MD, FACP Assistant Professor of Hematology and Oncology, Medical Director of Research, Karmanos Cancer Institute, Wayne State University School of Medicine

Mohammad Muhsin Chisti, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Suma Chinta, MD, MBBS Resident Physician, Department of Internal Medicine, St Joseph Mercy Oakland Hospital

Suma Chinta, MD, MBBS is a member of the following medical societies: American College of Physicians, Medical Council of India

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: Received salary from Medscape for employment. for: Medscape.

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Royal College of Physicians

Disclosure: Nothing to disclose.

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.

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