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DOI: 10.1055/s-0038-1665408
Free Protein S Deficiency Is a Risk Factor for Venous Thrombosis
Publication History
Received 29 1996
Accepted after resubmission 07 July 1997
Publication Date:
12 July 2018 (online)
Summary
A recent study suggests that protein S deficiency is not a risk factor for venous thrombosis. Since this unexpected finding would have important clinical implications if confirmed, we performed a case-control study with the aim to determine the prevalence of protein S deficiency in patients with thrombosis and in healthy individuals taken from the general population and the relative risk of thrombosis in protein S-deficient patients. Free protein S concentration was measured in 327 consecutive patients with at least one venous thrombotic episode and in 317 age- and sex-matched control individuals. Different normal reference ranges were obtained and adopted for men and women. Protein S deficiency was found in 3.1% (95% Cl: 1.5-5.2) of patients and in 1.3% of controls (95% Cl: 0.3-2.8). Ten patients and 4 control subjects had protein S deficiency, which determined a relative risk of thrombosis (sex- and age-adjusted odds ratio) of 2.4 (95% Cl: 0.8-7.9). When men and women were analyzed separately, the risk was 5.0 (95% CI: 0.6-43.6) and 1.6 (95% Cl: 0.4-6.7) respectively. PS-deficient men had more thrombotic episodes than women and later in life. Multivariate analysis established that sex was an independent determinant of the number of episodes, as was age, while PS deficiency was not. However sex and PS deficiency status were both determinants of age at first thrombotic episode.
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References
- 1 Dählbiick B, Stenllo J. The protein C anticoagulant system. In: The molecular basis of blood diseases. Stammatoyannopoulos G, Nienhuis AW, Majerus PW, Varmus H. (eds). W.B.Saunders; Philadelphia, PA: 1994. p. 599
- 2 Discipio RG, Hermodson MA, Yates SG, Davie EW. A comparison of human prothrombin, factorTX, factor X, and protein S. Biochemistry 1977; 16: 698-706
- 3 Harris KW, Esmon CT. Protein S is required for bovine platelets to support activated protein C binding and activity. J Biol Chem 1985; 260: 2007-2010
- 4 Heeb MJ, Rosing J, Bakker HM, Fernandez JA, Tans G, Griffin JH. Protein S binds to and inhibits factor Xa. Proc Natl Acad Sci USA 1994; 91: 2728-2732
- 5 Comp PC, Doray D, Patton D, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504-508
- 6 Broekmans AW, Bertina RM, Reinalda-Poot J, Engesser L, Muller HP, Leeuw JA, Michiels JJ, Brommer EJP, Briët E. Hereditary protein S deficiency and venous thrombo-embolism. A study in three Dutch families. Thromb Haemost 1985; 53: 273-277
- 7 Pabinger I, Kyrle PA, Heistinger M, Eichinger S, Wittman E, Lechner K. The risk of thromboembolism in asymptomatic patients with protein C and protein S deficiency: a prospective cohort study. Thromb Haemost 1994; 71: 441-445
- 8 Koster T, Rosendaal FR, Briët E, van derMeerFJM, Colly LP, Trienekens PH, Poort SR, Reitsma PH, Vandenbroucke JP. Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia study). Blood 1995; 85: 2756-2761
- 9 Fukudome K, Esmon CT. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 1994; 269: 26486-26491
- 10 Bakker H, Tans G, Janssen-Claessen T, Thomassen MCLGD, Hemker HC, Griffin JH, Rosinh J. The effect of phospholipids, calcium ions and protein S on rate constants of human factor Va inactivation by activated human protein C. Eur J Biochem 1992; 208: 171-178
- 11 Dahlbäck B. Inhibition of protein Ca cofactor function of human and bovine protein S by C4b-binding protein. J Biol Chem 1986; 261: 12022-12027
- 12 Hirsch RP, Riegelman RK. Statistical first aid. Blackwell Scientific Publications; Boston, MA: 1992
- 13 Zöller B, Garcia deFrutos P, Dahlbäck B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995; 85: 3524-3531
- 14 Boerger LM, Morris PC, Thumau GR, Esmon CT, Comp PC. Oral contraceptives and gender affect protein S status. Blood 1987; 69: 692-694
- 15 Garì M, Falkon L, Urrùtia T, Vallvé C, Borrell M, Fontcuberta J. The influence of low protein S levels in young women on the definition of the normal range. Thromb Res 1994; 73: 149-152
- 16 Falkon L, Garì M, Garcìa MoraJL, Calaf J, Rodriguez EspinosaJ, Oliver A, Fontcuberta J. The effect of endogenous estradiol levels on protein S concentration during a menstrual cycle and after gnRH analogues and gonadotropin therapy. Br J Haematol 1995; 90: 438-443
- 17 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 1988; 59: 18-22
- 18 Ben TalO, Zivelin A, Seligsohn U. The relative frequency of hereditary thrombotic disorders among 107 patients with thrombophilia in Israel. Thromb Haemost 1989; 61: 50-54
- 19 Heijboer H, Brandjes D, Büller HR, Sturk A, ten CateJW. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep- vein thrombosis. N Engl J Meed 1990; 323: 1512-1516
- 20 Tabemero MD, Tomas FJ, Alberca I, Orfao A, Borrasca AL, Vicente V. Incidence and clinical characteristics of hereditary disorders associated with venous thrombosis. Am J Hematol 1991; 36: 249-254