Thromb Haemost 1993; 70(02): 281-285
DOI: 10.1055/s-0038-1649566
Original Articles
Coagulation
Schattauer GmbH Stuttgart

Protein C Activity in Healthy Volunteers - Influence of Age, Sex, Smoking and Oral Contraceptives

R C Tait
The Department of Haematology, Royal Infirmary, Glasgow, Scotland
,
Isobel D Walker
The Department of Haematology, Royal Infirmary, Glasgow, Scotland
,
S I A M Islam
1   The Glasgow and West of Scotland Blood Transfusion Service, Law Hospital, Carluke, Scotland
,
Frances McCall
The Department of Haematology, Royal Infirmary, Glasgow, Scotland
,
J A Conkie
The Department of Haematology, Royal Infirmary, Glasgow, Scotland
,
M Wight
The Department of Haematology, Royal Infirmary, Glasgow, Scotland
,
R Mitchell
1   The Glasgow and West of Scotland Blood Transfusion Service, Law Hospital, Carluke, Scotland
,
J F Davidson
The Department of Haematology, Royal Infirmary, Glasgow, Scotland
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 28. September 1992

Accepted after revision 06. Februar 1993

Publikationsdatum:
04. Juli 2018 (online)

Summary

Interpretation of protein C (PC) levels in a given individual has several limitations. A normal PC activity does not necessarily exclude a genetic deficiency nor can a reduced level confirm it. Measuring PC amidolytic activity in 9,648 healthy blood donors has allowed identification of demographic factors which cause variation in PC activity and further hinder interpretation. PC activity displays a log normal distribution and significant variation with age. This is most marked in young adult males when mean PC activity rises from 0.86 iu/ml (15–19 years) to 1.04 iu/ml (45–49 years; P <0.0001). Pre-menopausal females, who for most age ranges, have mean PC activity below their male contemporaries, show a less marked rise with age until the menopause when PC activity rises further. The use of hormonal contraceptive preparations is associated with an increase in mean PC activity of 0.05–0.08 iu/ml while smoking habit has no influence on PC activity.

In view of these findings we strongly recommend the use of age and sex restricted reference ranges when interpreting PC activity.

 
  • References

  • 1 Comp PC, Esmon CT. Generation of fibrinolytic activity by infusion of activated protein C into dogs. J Clin Invest 1981; 68: 1221-1228
  • 2 Marlar RA, Kleiss AJ, Griffin JH. Mechanism of action of human activated protein C, a thrombin-dependent anticoagulant enzyme. Blood 1982; 59: 1067-1072
  • 3 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-1373
  • 4 Bertina RM, Broekmans AW, van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemostas 1982; 48: 1-5
  • 5 Horellou MH, Conard J, Bertina RM, Samama M. Congenital protein C deficiency and thrombotic disease in nine French families. Br Med J 1984; 289: 1285-1287
  • 6 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 1989; 73: 712-717
  • 7 Melissari E, Kakkar VV. Congenital severe protein C deficiency in adults. Br J Haematol 1989; 72: 222-228
  • 8 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 1991; 78: 890-894
  • 9 Miletich J, Sherman L, Broze G. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991-996
  • 10 Mannucci PM, Boyer C, Tripodi A, Vigano-D’Angelo S, Wolf M, Valsecchi C, D’Angelo A, Meyer D, Larrieu MJ. Multicenter comparison of five functional and two immunological assays for protein C. Thromb Haemostas 1987; 57: 44-48
  • 11 Tahara C, Kazama M, Miyajima Y, Matsumoto K, Abe T. Reference values of hemostasis related factors of healthy Japanese adults II. Protein C. Thromb Res 1991; 62: 345-351
  • 12 Mannucci PM, Vigano S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; ii: 463-467
  • 13 Clouse LH, Comp PC. The regulation of haemostasis: the Protein C system. N Engl J Med 1986; 314: 1298-1304
  • 14 Vigano-D’ AngeloS, Comp PC, Esmon CT, D’Angelo A. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest 1986; 77: 416-425
  • 15 McCall F, Conkie JA, Walker ID, Davidson JF. Measurement of protein C in plasma - a fully automated assay. Thromb Res 1987; 45: 681-685
  • 16 Griffin JH, Mosher DF, Zimmerman TS, Kleiss AJ. Protein C, an antithrombotic protein, is reduced in hospitalized patients with intravascular coagulation. Blood 1982; 60: 261-264
  • 17 Kumar S, Haigh JRM, Tate G, Boothby M, Joannes DN, Davies JA, Roberts BE, Feely MP. Effect of warfarin on plasma concentrations of vitamin K dependent coagulation factors in patients with stable control and monitored compliance. Br J Haematol 1990; 74: 82-85
  • 18 Malm J, Laurell M, Dahlback B. Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception. Br J Haematol 1988; 68: 437-443
  • 19 Pabinger-Fasching I, Lechner K, Neissner H, Schmidt R, Balzar E, Mannhalter C. High levels of plasma protein C in nephrotic syndrome. Thromb Haemostas 1985; 53: 5-7
  • 20 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefson DM, Powers P. Development of the human coagulation system in the full-term infant. Blood 1987; 70: 165-172
  • 21 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 1986; 109: 843-845
  • 22 Bertina RM, Broekmans AW, Krommenhoek-van Es C, van Wijngaarden A. The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. Thromb Haemostas 1984; 51: 1-5
  • 23 Marlar RA. Protein C in thromboembolic disease. Semin Thromb Hemostas 1985; 11: 387-393
  • 24 Marlar R, Endres-Brooks J, Miller C. Acquired deficiences of protein C antigen and the plasma inhibitor of activated protein C. Thromb Haemostas 1983; 50: 350
  • 25 Tait RC, Walker ID, Islam SAI, Mitchell R, Conkie JA, McCall F, Davidson JF. Age related changes in Protein C activity in healthy adult males. Thromb Haemostas 1991; 65: 326-327
  • 26 Scott BD, Esmon CT, Comp PC. The natural anticoagulant protein S is decreased in male smokers. Am Heart J 1991; 122: 76-80
  • 27 Huisveld IA, Hospers JEH, Meijers JCM, Starkenburg AE, Erich WBM, Bouma BN. Oral contraceptives reduce total protein S, but not free protein S. Thromb Res 1987; 45: 109-114
  • 28 Meade TW, Stirling Y, Wilkes H, Mannucci PM. Effects of oral contraceptives and obesity on protein C antigen. Thromb Haemostas 1985; 53: 198-199
  • 29 Gonzalez R, Alberca I, Vicente V. Protein C levels in late pregnancy, postpartum and in women on oral contraceptives. Thromb Res 1985; 39: 637-640
  • 30 Jespersen J, Petersen KR, Skouby SO. Effects of newer oral contraceptives on the inhibition of coagulation and fibrinolysis in relation to dosage and type of steroid. Am J Obstet Gynecol 1990; 163: 396-403
  • 31 Ford I, Li TC, Malia RG, Cooke ID, Preston FE. Changes in the natural inhibitors of coagulation, antithrombin III, protein C and protein S during treatment with danazol. Br J Haematol 1991; 77 (Suppl. 01) 61
  • 32 Gonzalez R, Alberca I, Sala N, Vicente V. Protein C deficiency - response to danazol and DDAVP. Thromb Haemostas 1985; 53: 320-322
  • 33 Esparaz B, Green D. A study of proteins C and S in patients with prostatic disease. Thromb Haemostas 1988; 60: 122
  • 34 Weeke B, Krasilnikoff PA. The concentration of 21 serum proteins in normal children and adults. Acta Med Scand 1972; 192: 149-155
  • 35 Hoogendoorn H, Toh CH, Nesheim ME, Giles AR. Alpha-2-macroglobulin binds and inhibits activated protein C. Blood 1991; 78: 2283-2290
  • 36 Marlar RA, Kressin DC. Activated protein C is not regulated by alpha-2-macroglobulin in plasma. Thromb Res 1989; 54: 177-186
  • 37 Lyngbye J, Kroll J. Quantitative Immunoelectrophoresis of proteins in serum from a normal population: season-, age-, and sex-related variations. Clin Chem 1971; 17: 495-500