Cigarette Smoking Sensitizes and Desensitizes Impedance-measured ADP-induced Platelet Aggregation in Whole Blood

Dan S Sharp; Neal L Benowitz; P M W Bath; John F Martin; Andrew D Beswick; Peter C Elwood

doi:10.1055/s-0038-1649805

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1995; 74(02): 730-735
DOI: 10.1055/s-0038-1649805

Original Article

Platelets

Schattauer GmbH Stuttgart

Cigarette Smoking Sensitizes and Desensitizes Impedance-measured ADP-induced Platelet Aggregation in Whole Blood

Dan S Sharp

¹The MRC Epidemiology Unit (South Wales), Llandough Hospital, Penarth, South Glamorgan, UK

,

Neal L Benowitz

²The Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, and the San Francisco General Hospital Medical Center, San Francisco, CA, USA

,

P M W Bath

³The Blood Pressure Unit, Department of Medicine, St.George’s Hospital Medical School, London, UK

⁴The Department of Medicine, King’s College School of Medicine and Dentistry, London, UK

,

John F Martin

⁴The Department of Medicine, King’s College School of Medicine and Dentistry, London, UK

,

Andrew D Beswick

¹The MRC Epidemiology Unit (South Wales), Llandough Hospital, Penarth, South Glamorgan, UK

,

Peter C Elwood

¹The MRC Epidemiology Unit (South Wales), Llandough Hospital, Penarth, South Glamorgan, UK

› Author Affiliations

Abstract

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Summary

The effect of smoking on platelet aggregation appears to produce conflicting results, with some studies indicating an enhancement and others a decrease of aggregation. This epidemiological study of 120 male smokers, a subset of the Caerphilly Heart Disease Study, examined the relationship of two dimensions of smoking (time proximity of last cigarette before venepuncture and serum nicotine concentration) with threshold dose of adenosine diphosphate (ADP) necessary to induce platelet aggregation in whole blood. Means (range) of ADP threshold dose and nicotine concentration were 1.66 (0.5-2.5, censored) μM and 12.2 (0-35.2) ng/ml. Men smoking within 30 min of venepuncture demonstrated lower ADP threshold doses (-0.48 μM lower [95% C. I.: -0.95, -0.02]) – reflecting increased sensitivity. Men with higher nicotine concentration had higher ADP threshold doses (Regression Coefficient: +0.032 μM per ng/ml [95% C. I.: 0.003, 0.062]) – reflecting decreased sensitivity. Men smoking 30 min or more before venepuncture who also had high nicotine concentration (25-30 ng/ml) demonstrated the highest ADP threshold doses compared to never smokers and to men smoking the previous day (≈2.20 vs 1.86 and 1.81 μM). Relations involving nicotine concentration do not necessarily reflect a pharmacological effect although the potential for a short term nicotine mediated tolerance effect cannot be dismissed. These observations support an hypothesis suggesting a temporal sequence of platelet sensitization and desensitization during smoking.

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References

References
1 Fielding JE. Smoking: Health effects and control. In: Maxcy-Rosenau-Last Public Health and Preventive Medicine. 13 edition Last JM, Wallace RB. eds East Norwalk, Connecticut: Appleton & Lange; 1992: 715-740
2 Yano K, MacLean CJ, Reed DM, Shimizu Y, Sasaki H, Kodama K, Kato H, Kagan A. A comparison of the 12-year mortality and predictive factors of coronary heart disease among Japanese men in Japan and Hawaii. Am J Epidemiol 1988; 127 (03) 476-487
3 Shaper AG, Pocock SJ, Walker M, Phillips AN, Whitehead TP, MacFarlane PW. Risk factors for ischemic heart disease: The prospective phase of the British Regional Heart Study. J Epidemiol Community Health 1985; 39: 197-209
4 Reed D, Marcus E, Hayashi T. Smoking as a predictor of atherosclerosis in the Honolulu Heart Program. In: Tobacco Smoking and Atherosclerosis: Pathogenesis and Cellular Mechanisms. Proceedings of an International Symposium on Tobacco Smoking and Atherosclerosis;Lexington, Kentucky 10.12.1989. New York, London, Washington DC, Boston: Plenum Publish Corp; 1990: 17-25
5 Miller GJ. Environmental influences on hemostasis and thrombosis: Diet and smoking. Ann Epidemiol 1992; 2: 387-391
6 Wilhelmsen L. Thrombocytes and coronary heart disease. Circulation (comment) 1991; 84 (02) 936-938
7 Foo LC, Roshidah I, Aimy MB. Platelets of habitual smokers have reduced susceptibility to aggregating agent. Thromb Haemost 1991; 65 (03) 317-319
8 Beswick A, Renaud S, Yarnell JW G, Elwood PC. Platelet activity in habitual smokers. Thromb Haemost 1991; 66 (06) 739
9 Foo LC. Reply to Beswick et al. Thromb Haemost 1991; 66 (06) 740
10 Elwood PC, Renaud S, Sharp DS, Beswick AD, O’Brien JR, Yarnell JW G. Ischemic heart disease and platelet aggregation: The Caerphilly Collaborative Heart Disease Study. Circulation 1991; 83: 38-44
11 Thaulow E, Erikssen J, Sandvik L, Stormorken H, Cohn PF. Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation 1991; 84: 613-617
12 Hanker LA, Mann KG. Thrombosis and Fibrinolysis. In: Thrombosis in Cardiovascular Disorders. Fuster V, Verstraete M. eds Philadelphia, Pennsylvania: Harcourt Brance Jovanovich, Inc; 1992: 6
13 Elwood PC, Beswick AD, Sharp DS, Yarnell JW G, Rogers S, Renaud S. Whole blood impedance platelet aggregometry and ischemic heart disease: The Caerphilly Collaborative Heart Disease Study. Arteriosclerosis 1990; 10: 1032-1036
14 Abbate R, Favilla S, Boddi M, Costanzo G, Prisco D. Factors influencing platelet aggregation in whole blood. Am J Clin Pathol 1986; 86: 91-96
15 Zatta A, Prosdocimi M, Bertele V, Bazzoni G, Del Maschio A. Inhibition of platelet function by polymorphonuclear leukocytes. J Lab Clin Med 1990; 116: 651-660
16 Levine PH. An acute effect of cigarette smoking on platelet function: A possible link between smoking and arterial thrombosis. Circulation 1973; 48: 619-623
17 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 (03) 389-395
18 Sharp DS, Beswick A, Renaud S, Toothill C, Elwood PC. Blood lead and platelet aggregation - evidence for a causal association. Thromb Haemost 1991; 66 (05) 604-608
19 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 (01) 44-48
20 Pittilo RM, Clark JM F, Harris D, Mackie IJ, Rowles PM, Machin SJ, Woolf N. Cigarette smoking and platelet adhesion. Br J of Haematol 1984; 58: 627-632
21 Taylor RR, Sturm M, Vandongen R, Strophair J, Beilin LJ. Whole blood platelet aggregation is not affected by cigarette smoking but is sex-related. Clin Experimental Pharmacol Physiol 1987; 14: 665-671
22 Schmidt KG, Rasmussen JW. Acute platelet activation induced by smoking: In vivo and ex vivo studies in humans. Thromb Haemost 1984; 52 (02) 279-282
23 Vicari AM, Margonato A, Macagni A, Luoni R, Seveso MP, Vicedomini G, Pozza G. Effects of acute smoking on the hemostatic system in humans. Clin Cardiol 1988; 11: 538-540
24 Davis JW, Arnold J. Time course of some effects of cigarette smoking on platelets. JInt Med 1992; 231: 31-36
25 Sharp DS, Beswick AD, O’Brien JR, Renaud S, Yarnell JW G, Elwood PC. The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: Evidence from the Caerphilly Collaborative Heart Disease Study. Thromb Haemost 1990; 64: 211-215
26 Caerphilly and Speedwell Collaborative Group. Caerphilly and Speedwell collaborative heart disease studies. J Epidemiol Community Health. 1984 38. 259-262
27 Cardinal DC, Flower RJ. The electronic aggregometer: A novel device for assessing platelet behavior in whole blood. J Pharmacol Methods 1980; 3: 135-158
28 Watts SE, Tunbridge LJ, Lloyd JV. Storage of platelets for tests of platelet function: Effects of pH on platelet aggregation and libration of β-thrombo-globulin. Thromb Res 1983; 29: 343-353
29 Cox DR, Oakes D. Analysis of survival data. In: Monographs on Statistics and Applied Probability. Cox DR, Hinkley DV, Rubin D, Silverman BW. eds London, New York: Chapman and Hall; 1985. 3-4 24-25
30 SAS Institute Inc. SAS/STAT User’s Guide. 4. Edition Volume 2 Cary, NC:: SAS Institute Inc; 1989
31 Jacob III P, Wilson M, Benowitz NL. Nicotine and cotinine determination in biologic fluids: An improved gas chromatographic method. J Chromatogr 1981; 222: 61-70
32 Benowitz NL. Pharmacologic aspects of cigarette smoking and nicotine addition. New Engl J Med 1988; 319: 1318-1330
33 Sharp DS, Hath PM W, Martin Jb, Beswiek AD, Sweelnam PM. Platelet and erythrocyte volume and count: Lpidemiological predictors of impedance measured ADP-induced platelet aggregation in whole blood. Platelets 1994; 5: 252-257
34 Mannucci L, Kedaelli R, Tremoli E. Effects of aggregating agents and of blood cells on the aggregation of whole blood by impedance technique. Thrombosis Research 1988; 52: 143-151
35 Blache D, Bouthillicr D, Davignon J. Acute influence of smoking on platelet behaviour, endothelium and plasma lipids and normalization by aspirin. Atherosclerosis 1992; 93: 179-188
36 Lassila R, Laustiola KL. Physical exercise provokes platelet desensiti/ation in men who smoke cigarettes involvement of sympathoadrcnergic mechanisms a study of monozygotic twin pairs discordant for smoking. Thromb Res 1988; 51: 145-155
37 Terres W, Becker BF, Schrödl W, Gerlaeh E. Inhibition of platelet aggregation following chronic in vivo treatment of rats with nicotine: prevention by simultaneous application of propranolol. J Cardiovasc Pharmacol 1989; 13: 233-237
38 bolts Jd, Boncbrake PC. The effects of cigarette smoke and nicotine on platelet thrombus formation in stenosed dog coronary arteries: inhibition with phcntolaminc. Circulation 1982; 65: 465-469
39 Pfueller SL, Burns P, Mak K, Firkin BG. PITeets of nicotine on platelet function. Haemostasis 1988; 18: 163-169
40 Schwartz J, Weiss ST. Host and environmental factors influencing the peripheral blood leukocyte count. Am I Epidemiol 1991; 134: 1402-1409
41 Petitti DB, Kipp H. The leukocyte count: associations with intensity of smoking and persistence of effect after quitting. Am J Epidemiol 1986; 123: 89-95
42 Scheer P. über den Linfluß des Nikulins auf das leukozytäre Blutbild des Mensehen. Z Gesamle Exp Med 1940; 107: 219-227
43 Abboud RT, Tharwat F, Johal S, Richter A, Gibson N. Effect of smoking on plasma neutrophil elastase levels. J Lab Clin Med 1986; 108: 294-300
44 Hanker LA, Mann KG. Thrombosis and Fibrinolysis. In: Thrombosis in Cardiovascular Disorders. Fuster V, Verslraelc M. eds Philadelphia; W. B. Saunders Company: Harcourl Brace Jovanovich, Inc. 1992: 13
45 Salvemini D, de Nucci G, Gryglewski RJ, Vane JR. Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxidelike factor. Proc Nall Acad Sci 1989; 86: 6328-6332
46 Oudinct JP, Sraer J, Bens M, Ardaillou R. Influence of polymorphonuclear leukocytes on the metabolism of arachidonalc in human platelets. Thromb Hacmost 1988; 60: 59-62
47 Wu KK, Papp AC, Manner Cc, Hall ER. Interaction between lymphocytes and platelets in the synthesis of prostacyclin. J Clin Invest 1987; 79: 1601-1606
48 Del Maschio A, Bazzoni G, Bertelé V. Investigation of platelet/leukocyte interaction by whole blood aggregometry. Thromb Haemost 1990; 64: 487
49 Benowitz NL, Jacob III P, Jones RT, Rosenberg J. Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J Pharmacol Exp Ther 1982; 221: 368-372