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.
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.
Gerrard
J M
JM
Department of Pediatrics, University of Manitoba, Winnipeg, Canada.
Taback
S
S
Singhroy
S
S
Docherty
J C
JC
Kostolansky
I
I
McNicol
A
A
Kobrinsky
N L
NL
McKenzie
J K
JK
Rowe
R
R
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis / Q000097:blood*; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001760:Bleeding Time; D003920:Diabetes Mellitus / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D012907:Smoking; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood*; D013997:Time Factors
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin