Copyright © 2001 by the European Society of Cardiology.
Acute effects of cigarette smoking on platelet-dependent thrombin generation
Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
revised September 13, 1999; accepted September 15, 1999
Abstract
Aims Thrombin is an important factor in the pathogenesis of thrombotic diseases. To clarify whether smoking has an effect in platelet-dependent thrombogenesis, we studied the acute effects of smoking on platelet-dependent thrombin level in smokers.
Methods and Results Subjects consisted of ten smokers and nine non-smokers. Platelet-dependent thrombin level measured after overnight fasting was greater in smokers than in non-smokers (smokers vs non-smokers, 121±47 vs 56±5mIU.ml1,P <0·01). When subjects in the smokers group smoked two cigarettes containing 0·9mg of nicotine per cigarette, platelet-dependent thrombin levels showed a transient three-fold increase in blood samples obtained immediately after smoking (365±76mIU.ml1, P<0·001). Thrombin levels in the blood samples obtained 10min and 30min after smoking were less than that in the samples obtained immediately after smoking ceased, but were not significantly different from those in the samples obtained before smoking. Blood nicotine level increased significantly immediately after smoking (P<0·001), and plasma protein C activity decreased significantly 30min after smoking (P<0·05). When nicotine or cotinine was added to the platelet-rich plasma of non-smokers ex vivo, the platelet-dependent thrombin level increased significantly (P<0·002).
Conclusion Platelet-dependent thrombin level is enhanced in smokers, even when not smoking, when compared with non-smokers and increases immediately after smoking. Increases in nicotine and cotinine levels caused by smoking induced a prothrombotic state in smokers via increased platelet-dependent thrombogenesis.
Key Words: Thrombin, smoking, platelet, thrombogenesis, cigarette
f1 Correspondence: Kyozo Ishikawa, MD, Second Department of Internal Medicine, Kyorin University School Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
References
- Kleinman, JC, Feldman, JJ, Monk, MA, Trends in smoking and ischemic heart disease mortality: recent trends of major coronary risk factors and CHD mortality in the USA and other industrialized countries, Washington, DC, National Institute of Health, 1979
- Wilhelmsen L. Coronary heart disease: epidemiology of smoking and intervention studies of smoking. Am Heart J. 1988;115:242249[CrossRef][ISI][Medline]
- Celermajer DS, Sorensen KE, Georgakopoulos D. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 1993;88:21492155
[Abstract/Free Full Text] - Kiowski W, Linder L, Stoschisky K. Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers. Circulation. 1994;90:2734
[Abstract/Free Full Text] - Zeiher AM, Schaechinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation. 1995;92:10941100
[Abstract/Free Full Text] - Fitzgerald GA, Oates JA, Nowak J. Cigarette smoking and hemostatic function. Am Heart J. 1988;115:267271[CrossRef][ISI][Medline]
- Fuster V, Chesebro JH, Frye RL, Elveback LR. Platelet survival and the development of coronary artery disease in the young adults: effects of cigarette smoking, strong family history and medical therapy. Circulation. 1981;63:546551
[Abstract/Free Full Text] - Zwaal RFA, Comfurius P, Bevers EM. Platelet procoagurant activity and microvesicle formation. Its putative role in hemostasis and thrombosis. Biochem Biophys Acta. 1992;1180:18[Medline]
- Aoki I, Aoki N, Kawano K. Platelet-dependent thrombin generation in patients with hyperlipidemia. J Am Coll Cardiol. 1997;30:9196[Abstract]
- Aoki I, Shimoyama K, Aoki N. Platelet-dependent thrombin generation in patients with diabetes mellitus: effects of glycemic control on coagulability in diabetes. J Am Coll Cardiol. 1996;26:560566
- Aronson DL, Chang P, Kessler CM. Platelet-dependent thrombin generation after in vitro fibrinolytic treatment. Circulation. 1992;85:17061712
[Abstract/Free Full Text] - Hariharan M, VanNoord T. liquid-chromatographic determination of nicotine and cotinine in urine from passive smokers: comparison with gas chromatography with nitrogen-specific detector. Clin Chem. 1991;37:12761280
[Abstract/Free Full Text] - Mattinoli JL, Stocker K. Fast functional protein C assay using Protac, a novel protein C activator. Thromb Res. 1986;43:253264[CrossRef][ISI][Medline]
- Kannel WB, McGee DL, Castelli WP. Latest perspectives on cigarette smoking and cardiovascular disease: the Framingham Study. J Cardiac Rehabil. 1984;4:267277
- Kannel WB. Update on the role of cigarette smoking in coronary artery disease. Am Heart J. 1981;101:319328[CrossRef][ISI][Medline]
- Zimmerman M, McGeachie J. The effect of nicotine on aortic endothelium: a quantitative ultrastructural study. Atherosclerosis. 1987;63:3341[CrossRef][ISI][Medline]
- Astrup P, Kjeldsen K. Model studies linking carbon monoxide and/or nicotine to arteriosclerosis and cardiovascular disease. Prev Med. 1979;8:295302[CrossRef][ISI][Medline]
- Reilly M, Delanty N, Lawson JA, Fitzgerald GA. Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation. 1996;94:1925
[Abstract/Free Full Text] - Craig WY, Palpmaki GE, Haddow JE. Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. Br Med J. 1989;298:784788[ISI][Medline]
- Kimura S, Nishinaga M, Ozawa T, Shimada K. Thrombin generation as an acute effect of cigarette smoking. Am Heart J. 1994;128:711[CrossRef][ISI][Medline]
- Renaud S, Blache D, Dumont E, Thevenon C, Wissendanger T. Platelet function after cigarette smoking in relation to nicotine and carbon monoxide. Clin Pharmacol Ther. 1984;36:389395[ISI][Medline]
- Folts DJ, Bonebrake FC. The effects of cigarette smoke and nicotine on platelet thrombus formation in stenosed dog coronary arteries: inhibition with phentolamine. Circulation. 1982;62:465470
- Foo LC, Roshidah I, Aimy MB. Platelets of habitual smokers have reduced susceptibility to aggregating agent. Thromb Haemost. 1991;65:317319[ISI][Medline]
- Siess W, Lorenz R, Roth P, Weber PC. Plasma catecholamines, platelet aggregation and associated thromboxane formation after physical exercise, smoking or norepinephrine infusion. Circulation. 1982;66:4448
[Abstract/Free Full Text] - Hung J, Lam JYT, Lacoste L, Letchacovski G. Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin. Circulation. 1995;92:24322436
[Abstract/Free Full Text] - Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. (Part 1). N Engl J Med. 1992;326:242250[ISI][Medline]
- Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. (Part 2). N Engl J Med. 1992;326:310318[ISI][Medline]
- Cryer PE, Haymond MW, Santiago JV, Shah SD. Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. N Engl J Med. 1976;295:573577[Abstract]
- Nicod P, Rehr R, Winniford MD, Campbell WB, Firth BG, Hillis LD. Acute systemic and coronary hemodynamic and serologic responses to cigarette smoking in long-term smokers with atherosclerotic coronary artery disease. J Am Coll Cardiol. 1984;4:964971[Abstract]
- Yotsukura M, Koide Y, Fujii K. Heart rate variability during the first month of smoking cessation. Am Heart J. 1998;135:10041009[CrossRef][ISI][Medline]
This article has been cited by other articles:
![]() |
T. Raupach, K. Schafer, S. Konstantinides, and S. Andreas Secondhand smoke as an acute threat for the cardiovascular system: a change in paradigm Eur. Heart J., February 2, 2006; 27(4): 386 - 392. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. K. MacCallum Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers Proceedings of the ATS, April 1, 2005; 2(1): 34 - 43. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. F. Tapson The Role of Smoking in Coagulation and Thromboembolism in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 71 - 77. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Singhal, S. Bevan, T. Barrick, P. Rich, and H. S. Markus The influence of genetic and cardiovascular risk factors on the CADASIL phenotype Brain, September 1, 2004; 127(9): 2031 - 2038. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Suwansaksri, V. Wiwanitkit, and S. Soogarun Effect of Smoking on Platelet Count and Platelet Parameters: An Observation Clinical and Applied Thrombosis/Hemostasis, July 1, 2004; 10(3): 287 - 288. [Abstract] [PDF] |
||||
![]() |
D. Rubenstein, J. Jesty, and D. Bluestein Differences Between Mainstream and Sidestream Cigarette Smoke Extracts and Nicotine in the Activation of Platelets Under Static and Flow Conditions Circulation, January 6, 2004; 109(1): 78 - 83. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. von Kanel and J. E. Dimsdale Hemostatic Alterations in Patients With Obstructive Sleep Apnea and the Implications for Cardiovascular Disease Chest, November 1, 2003; 124(5): 1956 - 1967. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Tsiara, M. Elisaf, and D. P. Mikhailidis Influence of Smoking on Predictors of Vascular Disease Angiology, September 1, 2003; 54(5): 507 - 530. [Abstract] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||






