Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking.
OBJECTIVE
The purpose of this study was to examine the possible role of nicotine in enhancing coagulation and to assess the potential cardiovascular toxicity of transdermal nicotine therapy for smoking cessation.


BACKGROUND
Cigarette smoking increases the risks of acute coronary events. A likely contributing mechanism is activation of coagulation. The role of nicotine in enhancing coagulability has not been resolved.


METHODS
We compared in a crossover study the effects of cigarette smoking, transdermal nicotine and placebo transdermal nicotine, each for 5 days, in 12 healthy smokers.


RESULTS
Cigarette smoking increased the urinary excretion of 11-dehydro-thromboxane B2 (reflecting thromboxane A2 generation) and increased plasma concentration of the platelet alpha-granule constituents, platelet factor 4 and beta-thromboglobulin, compared with placebo treatment, indicating in vivo platelet activation. Cigarette smoking was also associated with higher levels of fibrinogen in plasma. Transdermal nicotine produced plasma levels of nicotine in the same range as those during smoking but had no effect on thromboxane A2 metabolite excretion, platelet alpha-granule release or plasma fibrinogen, compared with placebo. Excretion of 2,3-dinor-6-keto-PGF1 alpha (reflecting prostacyclin generation) was not significantly influenced by any treatment. These results suggest that nicotine as such is not responsible for the platelet activation or elevation of plasma fibrinogen seen in smokers. However, we cannot exclude the possibility that intermittent bolus-like dosing of nicotine from cigarettes could have different effects from those produced by continually released transdermal nicotine. Other findings were that cigarette smoking and transdermal nicotine treatment were both associated with a higher white blood cell count compared with the placebo patch condition, suggesting a direct effect of nicotine to increase circulating white cells. Factor VII coagulant activity (VIIc) was significantly lower during cigarette smoking, than during either nicotine or placebo patch conditions.


CONCLUSIONS
Transdermal nicotine has less effect on platelet activation and catecholamine release than does cigarette smoking, and its use in smoking cessation treatment of patients with coronary heart disease is likely to be safer than cigarette smoking.
Benowitz
N L
NL
Division of Clinical Pharmacology and Experimental Therapeutics, San Francisco General Hospital Medical Center, California 94110.
Fitzgerald
G A
GA
Wilson
M
M
Zhang
Q
Q
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000097:blood; D003327:Coronary Disease / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D015777:Eicosanoids / Q000096:biosynthesis* / Q000652:urine; D005167:Factor VII / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D019007:P-Selectin; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000032:analysis; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood* / Q000188:drug therapy / Q000652:urine; D016540:Smoking Cessation / Q000379:methods; D013928:Thromboxane A2 / Q000097:blood / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D001620:beta-Thromboglobulin / Q000032:analysis
D015815:Cell Adhesion Molecules; D015777:Eicosanoids; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D009538:Nicotine; D005167:Factor VII; D005340:Fibrinogen