Background: Protein C (PC) with its cofactor free protein S (FPS) are important anticoagulants. Any defect in the PC system is a risk factor for venous thrombosis. Aims: To assess the effect of intensity of smoking, and the dose-response for the number of cigarettes smoked on PC and FPS plasma levels. Methods: A comparative study was designed and carried out on a convenient sample of 50 healthy non-smokers and 150 non-symptomatic Jordanian male smokers. PC and FPS levels were measured using an automated system (Stago Analyzer, USA). Results: The plasma level of PC among smokers was 7.2% lower than that among non-smokers (p = 0.02). Moreover, smokers had 15.6% lower circulating FPS than non-smokers (p = 0.001). Furthermore, data showed significant negative correlations between both PC and FPS levels and the intensity of smoking (r = –0.21%, r = –0.23%, respectively; p = 0.01) and the period of smoking (r = –0.15%, r = –0.23%, respectively; p = 0.01, 0.12, respectively). Conclusions: The PC and FPS plasma levels were significantly lower in smokers than non-smokers. Both PC and FPS levels correlated inversely with the period and intensity of smoking, and FPS was more sensitive to smoking than PC.

Keywords:
Activated protein C, Free protein S, Smoking
1.
World Health Organization: Tobacco or Health: A Global Status Report. Geneva, World Health Organization, 1997.
2.
Abbas A, Kharabsha S: Morbidity and Mortality Survey. Jordan, Ministry of Health, 1996, unpubl study.
3.
Ajlouni K, Jaddou H, Batieha A: Obesity in Jordan. Int J Obes 1998;22:624–628.
4.
Bauer KA, Rosenberg RD: The pathophysiology of the prethrombotic state in humans: Insights gained from studies using markers of hemostatic system activation. Blood 1987;70:343–350.
5.
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.
6.
Branson HE, Katz J, Marble R, Griffin JH: Inherited protein C deficiency and a coumarin-responsive chronic relapsing purpura fulminans syndrome in a neonate. Lancet 1983;ii:1165–1168.
7.
Bertina RM, Broekmans AW, van der Linden IK, Mertens K: Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 1982;48:1–5.
8.
Furie B, Bouchard BA, Furie BC: Vitamin K-dependent biosynthesis of gamma carboxyglutamic acid. Blood 1999;93:1798–1808.
9.
Dahlbäck B: Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system. Thromb Haemost 1991;66:49–61.
10.
Rezende SM, Simmonds RE, Lane DA: Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S–C4b binding protein complex. Blood 2004;103:4.
11.
Borgel D, Gandrille S, Aiach M: Protein S deficiency. Thromb Haemost 1997;78:351–356.
12.
Lee J, Kim S, Sung Kim J: Sagittal sinus thrombosis associated with transient free protein S deficiency after L-asparaginase treatment: case report and review of the literature. Clin Neurol Neurosurg 2000;102:33–36.
13.
D’Angelo A, Della Valle P, Crippa L, Pattarini E, Grimaldi LM, Vigano D’Angelo S: Autoimmune protein S deficiency in a boy with severe thromboembolic disease. N Engl J Med 1993;328:1753–1757.
14.
Deitcher SR, Erban JK, Limentani SA: Acquired free protein S deficiency associated with multiple myeloma: a case report. Am J Hematol 1996;51:319–323.
15.
Erkan D, Zhang HW, Shirky RC, Merrill JT: Dual antibody reactivity to beta2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome. Lupus 2002;11:215–220.
16.
Song KS, Park YS, Kim HK: Prevalence of antiprotein S antibodies in patients with systemic lupus erythematosus. Arthritis Rheum 2000;43:557–560.
17.
Fernandez JA, Gruber A, Heeb MJ, Griffin JH: Protein C pathway impairment in nonsymptomatic cigarette smokers. Blood Cells Mol Dis 2002;29:73–82.
18.
Scott BD, Esmon CT, Comp PC: The natural anticoagulant protein S is decreased in male smokers. Am Heart J 1991;122:76–80.
19.
Esmon CT: The protein C pathway. Chest 2003;124:26S–32S.
20.
Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT: The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA 1996;93:10212–10216.
21.
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.
22.
Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G: Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984;311:501–505.
23.
Benowitz NL, FitzGerald GA, Wilson M, Zhang QI: Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking. J Am Coll Cardiol 1993;22:1159–1167.
24.
Branson HE, Katz J, Marble R, Griffin JH: Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983;ii:1165–1168.
25.
Greengard JS, Sun X, Xu X, Fernandez JA, Griffin JH, Evatt B: Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 1994;343:1361–1362.
26.
Glaser CB, Morser J, Clarke JH, Blasko E, McLean K, Kuhn I, Chang RJ, Lin JH, Vilander L, Andrews WH: Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity: a potential rapid mechanism for modulation of coagulation. J Clin Invest 1992;90:2565–2573.
27.
Díez N, Montes R, Alonso A, Medina P, Navarro S, España F, Hermida J: Association of increased fibrinogen concentration with impaired activation of anticoagulant protein C. J Thromb Haemost 2006;4:398–402.
28.
Jimenez Ruiz CA, Rajas O, Ruiz A, Ramos A, Florez S, Ramos L, Solano S, Fornies E: Bronchoalveolar lavage in smokers: quantification of alveolar macrophages and neutrophils as markers of bronchial obstruction. In Vivo 1998;12:427–430.
29.
Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P, Marcucci G, Wu KK: Associations of factor VIII and von Willebrand factor with age, race, sex and risk factors for atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost 1993;70:380–385.
© 2010 S. Karger AG, Basel
2010
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.