PDF herunterladen
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)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 7 Melissari E, Kakkar VV. Congenital severe protein C deficiency in adults. Br J Haematol 1989; 72: 222-228
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 12 Mannucci PM, Vigano S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; ii: 463-467
    PubMedSuche in Google Scholar
  • 13 Clouse LH, Comp PC. The regulation of haemostasis: the Protein C system. N Engl J Med 1986; 314: 1298-1304
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 23 Marlar RA. Protein C in thromboembolic disease. Semin Thromb Hemostas 1985; 11: 387-393
    Thieme ConnectPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 26 Scott BD, Esmon CT, Comp PC. The natural anticoagulant protein S is decreased in male smokers. Am Heart J 1991; 122: 76-80
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 32 Gonzalez R, Alberca I, Sala N, Vicente V. Protein C deficiency - response to danazol and DDAVP. Thromb Haemostas 1985; 53: 320-322
    PubMedSuche in Google Scholar
  • 33 Esparaz B, Green D. A study of proteins C and S in patients with prostatic disease. Thromb Haemostas 1988; 60: 122
    PubMedSuche in Google Scholar
  • 34 Weeke B, Krasilnikoff PA. The concentration of 21 serum proteins in normal children and adults. Acta Med Scand 1972; 192: 149-155
    PubMedSuche in Google Scholar
  • 35 Hoogendoorn H, Toh CH, Nesheim ME, Giles AR. Alpha-2-macroglobulin binds and inhibits activated protein C. Blood 1991; 78: 2283-2290
    PubMedSuche in Google Scholar
  • 36 Marlar RA, Kressin DC. Activated protein C is not regulated by alpha-2-macroglobulin in plasma. Thromb Res 1989; 54: 177-186
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar