Rheumatology International

, Volume 27, Issue 1, pp 39–43 | Cite as

Decreased protein S activity is related to the disease activity of Behcet’s disease

  • Seong Ryul Kwon
  • Mie Jin Lim
  • Shin Goo Park
  • Yeon Sook Moon
  • Won ParkEmail author
Original Article


We wanted to see whether the active inflammation in Behcet’s disease (BD) can cause a thrombotic disorder by decreasing the protein S (PS) activity, and we evaluated the relationship between the decreased PS activity and the disease activity of BD. We included 122 patients with BD whose PS activity levels were measured. In 51 patients, the PS activity was measured again when there were changes in the number of items of “The Behcet’s Disease Current Activity Form (BDCAF)”. The thrombosis rate was 2.5% (3/122), and the PS activity was low in all three of the patients with thrombosis. The incidence of low PS activity in the total 122 BD patients was 27% (33/122). The incidence of the low PS activity in the active BD patients was 33.7% (31/92), and this was significantly more frequent than in the inactive BD patients, (6.7%, 2/30) (χ2-test, P value = 0.0038). The decrease of PS activity had good correlation with the increase of the number of BDCAF items (r = −0.351, P value = 0.012). The PS activity decrease is related to the BD activity. The low PS activity can be the risk factor for thrombotic disorder and also the activity marker for BD and other inflammatory diseases.


Behcet’s disease Disease activity Protein S activity Thrombosis 


  1. 1.
    Kaklamani VG, Vaiopoulos G, Kaklamanis PG (1998) Behcet’s disease. Semin Arthritis Rheum 27:197–217PubMedCrossRefGoogle Scholar
  2. 2.
    Kluft C, Michiels JJ, Wijngaards G (1980) Factual or artificial inhibition of fibrinolysis and the occurrence of venous thrombosis in 3 cases of Behcet’s disease. Scand J Haematol 25:423–430PubMedCrossRefGoogle Scholar
  3. 3.
    Koc Y, Gullu I, Akpek G, Akpolat T, Kiraz S, Batman F et al (1992) Vascular involvement in Behcet’s disease. J Rheumatol 19:402–410PubMedGoogle Scholar
  4. 4.
    Lie JT (1992) Vascular involvement in Behcet’s disease: arterial and venous and vessels of all sizes. J Rheumatol 19:341–343PubMedGoogle Scholar
  5. 5.
    Wechsler B, Vidailhet M, Piette JC, Bousser MG, Dell IB, Blentry O et al (1992) Cerebral venous thrombosis in Behcet’s disease: clinical study and long-term follow-up of 25 cases. Neurol 42:614–618Google Scholar
  6. 6.
    Hampton KK, Chamberlain MA, Menon DK, Davis JA (1991) Coagulation and fibrinolytic activity in Behcet’s disease. Thromb Haemost 66:292–294PubMedGoogle Scholar
  7. 7.
    Ozoran K, Duzgun N, Gurler A, Tutkak H, Tokgoz G (1995) Plasma von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and antithrombin III levels in Behcet’s disease. Scand J Rheumatol 24:376–382PubMedGoogle Scholar
  8. 8.
    Oner AF, Gurgey A, Gurler A, Mesci L (1998) Factor V Leiden mutation in patients with Behcet’s disease. J Rheumatol 25:496–498PubMedGoogle Scholar
  9. 9.
    Gul A, Ozbek U, Ozturk C, Inanc M, Konkce M, Ozcelik T (1996) Coagulation factor V mutation increases the risk of venous thrombosis in Behcet’s disease. Br J Rheumatol 35:1178–1180PubMedCrossRefGoogle Scholar
  10. 10.
    Mader R, Ziv M, Adawi M, Mader R, Lavi I (1992) Thrombophilic factors and their relation to thromboembolic and other clinical manifestations in Behcet’s disease. J Rheumatol 26:2404–2408Google Scholar
  11. 11.
    Sengul N, Demirer S, Yerdel MA, Terzioglu G, Akin B, Gurler A et al (2000) Comparison of coagulation parameters for healthy subject and Behcet’s disease patients with and without vascular involvement. World J Surg 24:1584–1588PubMedCrossRefGoogle Scholar
  12. 12.
    Demier S, Sengul N, Yerder MA, Tuzuner A, Ulus AT, Gurler A et al (2000) Haemostatis in patients with Behcet’s disease. Eur J Vasc Endovasc Surg 19:570–574CrossRefGoogle Scholar
  13. 13.
    Borgel D, Gandrille S, Aiach M (1997) Protein S deficiency. Thromb Haemost 78:351–356PubMedGoogle Scholar
  14. 14.
    Lee JH, Kim SW, Kim JS (2000) Sagittal sinus thrombosis associated with transient free protein S deficiency after l-asparaginase treatment: case report and review of the literature. Clin Neurol Neurosurg 102:33–36PubMedCrossRefGoogle Scholar
  15. 15.
    D’Angelo A, Valle PD, Crippa L, Pattarini E, Grimaldi L, D’Angelo SV (1993) Autoimmune protein S deficiency in a boy with severe thromboemblimc disease. N Engl J med 328:1753–1757PubMedCrossRefGoogle Scholar
  16. 16.
    Stahl CP, Wideman CS, Spira TJ, Haff EC, Hixon GJ, Evatt BL (1993) Protein S deficiency in men with long-term human immunodeficiency virus infection. Blood 81:1801–1807PubMedGoogle Scholar
  17. 17.
    Nguyen P, Reynaud J, Pouzol P, Munzer M, Richard O, Francois P (1994) Varicella and thrombotic complications associated with transient protein C and protein S deficiencies in children. Eur J Pediatr 153:646–649 PubMedCrossRefGoogle Scholar
  18. 18.
    Deitcher SR, Erban JK, Limentani SA (1996) Acquired free protein S deficiency associated with multiple myeloma: a case report. Am J Hematol 51:319–323PubMedCrossRefGoogle Scholar
  19. 19.
    Song KS, Park YS, Kim HK (2000) Prevalence of anti-protein S antibodies in patients with systemic lupus erythematosus. Arthritis Rheum 43:557–560PubMedCrossRefGoogle Scholar
  20. 20.
    International Study Group for Behcet’s Disease (1990) Criteria for diagnosis of Behcet’s disease. Lancet 335:1078–1080Google Scholar
  21. 21.
    Lawton G, Bhakta BB, Chamberlain MA, Tennant A (2004) The Behcet’s Disease activity index. Rheumatol 43:73–78CrossRefGoogle Scholar
  22. 22.
    Lundwall A, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlback B et al (1986) Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc Natl Acad Sci USA 83:6716–6720PubMedCrossRefGoogle Scholar
  23. 23.
    Webb JH, Blom AM, Dahlback B (2002) Vitamin K-dependent protein S localizing complement regulator C4b-binding protein to the surface of apoptotic cells. J Immunol 169:2580–2586PubMedGoogle Scholar
  24. 24.
    Anderson HA, Maylock CA, Williams JA, Paweletz CP, Shu H, Shacter E (2003) Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat immunol 4:87–91PubMedCrossRefGoogle Scholar
  25. 25.
    Ohkohchi K, Tornuki W, Tagami H (1989) Plasma concentration of complement-modulation proteins (C1 inhibitor, C4 binding protein, factor H and factor I) in inflammatory dermatoses with special reference to psoriasis. Dermatologica 179(Suppl 1):30–34PubMedCrossRefGoogle Scholar
  26. 26.
    Kim HA, Choi KW, Song YW (1997) Arthropathy in Behcet’s disease. Scand J Rheumatol 26:125–129PubMedCrossRefGoogle Scholar
  27. 27.
    Lee YJ, Kang SW, Yang JI, Choi YM, Sheen D, Lee EB et al (2002) Coagulation parameters and plasma total homocysteine levels in Behcet’s disease. Thromb Res 106:19–24PubMedCrossRefGoogle Scholar
  28. 28.
    Ozatli D, Sayinalp N, Buyukasik Y, Karakus S, Haznedaroglu IC, Kirazli S et al (2002) Unchanged global fibrinolytic capacity despite increased factor VIIa activity in Behcet’s disease: evidence of a prethrombotic state. Rheumatol Int 21:137–140PubMedCrossRefGoogle Scholar
  29. 29.
    Yazici C, Kose K, Calis M, Demlr M, Kirnap M, Ates F (2004) Increased advanced oxidation protein products in Behcet’s disease: a new activity marker? Br J Dermatol 151:105–111PubMedCrossRefGoogle Scholar
  30. 30.
    Duzgun N, Ayaslioglu E, Tutkak H (2004) Serum soluble CD30 levels in Behcet’s disease. Clin Exp Rheumatol 22(Suppl 34):S17–20PubMedGoogle Scholar
  31. 31.
    Ozoran K, Duzgun N, Tutkak H, Gurler A, Tokgoz G (1996) Fibronectin and circulation immune complexes in Behcet’s disease. Rheumatol Int 15:221–224PubMedCrossRefGoogle Scholar
  32. 32.
    Chang HK, Cheon KS (2002) The clinical significance of a pathergy reaction in patients with Behcet’s disease. J Korean Med Sci 17:371–374PubMedGoogle Scholar
  33. 33.
    Hamuryndan V, Fresko I, Direskeneli H, Tenant MJ, Yurdakul S, Akoglu T et al (1999) Evaluation of the Turkish translation of a disease activity form for Behcet’s syndrome. Rheumatol 38:374–376Google Scholar
  34. 34.
    Bhakta BB, Brennan P, James TE, Chamberlain MA, Noble BA, Silman AJ (1999) Behcet’s disease: evaluation of a new instrument to measure clinical activity. Rheumatol 38:728–733CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Seong Ryul Kwon
    • 1
  • Mie Jin Lim
    • 1
  • Shin Goo Park
    • 2
  • Yeon Sook Moon
    • 3
  • Won Park
    • 1
    Email author
  1. 1.Division of Rheumatology, Department of Internal Medicine, College of MedicineInha UniversityInchonSouth Korea
  2. 2.Department of Occupational and Environmental Medicine, College of MedicineInha University HospitalInchonSouth Korea
  3. 3.Department of Laboratory Medicine, College of MedicineInha University HospitalInchonSouth Korea

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