Circulation, Vol 79, 29-38, Copyright © 1989 by American Heart Association
JM Gerrard, S Taback, S Singhroy, JC Docherty, I Kostolansky, A McNicol, NL Kobrinsky, JK McKenzie and R Rowe
The effects of smoking, aspirin ingestion, and sex differences on bleeding
times and bleeding time thromboxane B2 and 6-keto- prostaglandin (PG)F1
alpha production were examined. Nonsmoking men produced more thromboxane B2
(3.99 +/- 0.76 ng/ml) than nonsmoking women (2.13 +/- 0.24 ng/ml). Female
smokers produced more thromboxane B2 (5.01 +/- 0.97 ng/ml) than nonsmoking
women. Twenty-four hours after a single dose of 600 mg aspirin, in vitro
production of thromboxane B2 in response to collagen fell by 95%, whereas
in vivo production of thromboxane B2 and 6-keto-PGF1 alpha in bleeding time
blood fell by 87% and 66%, respectively. Subjects with the lowest absolute
levels of thromboxane B2 24 hours after aspirin were also those with the
longest postaspirin bleeding times. Recovery of 6-keto-PGF1 alpha
production was faster than recovery of thromboxane B2 production, but
6-keto-PGF1 alpha production for most subjects was still below basal 72
hours after aspirin. The influence of two different doses of long-term
aspirin (80 mg every other day and 325 mg daily) on the in vivo production
of thromboxane B2 and 6-keto-PGF1 alpha was studied in normals and
diabetics. After 14 days of 80 mg aspirin every other day, thromboxane B2
and 6-keto-PGF1 alpha production were both substantially inhibited (93% and
78%, respectively). After 14 days of 325 mg aspirin daily, thromboxane B2
production was similarly substantially inhibited (93%), whereas 6-keto-PGF1
alpha was significantly less affected (only 45% inhibition). Study of a
second group of five normal subjects confirmed that 6-keto-PGF1 alpha
production was significantly inhibited 24 hours after the first dose of 325
mg aspirin but was not significantly less than basal after 14 days of 325
mg aspirin. The results suggest that 325 mg aspirin daily is more
antithrombotic compared with 80 mg every other day due to the superior
preservation of prostacyclin production.
ARTICLES
In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin
Department of Pediatrics, University of Manitoba, Winnipeg, Canada.
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