Dose-related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy.
BACKGROUND
The purpose of this study was to determine which low dose of low dose aspirin (LDA) optimized the urinary prostacyclin (PGI2)/thromboxane (TXA2) ratio and minimized evidence of platelet aggregation during normal late pregnancy.


METHODS
Twelve women with uncomplicated singleton pregnancies between 28 and 34 weeks gestation participated in a randomized blinded study. Blood samples for salicylate levels were obtained pretreatment, 4 hours and 7 days after administration of placebo, 20mg, 40mg or 80mg of aspirin. Twenty-four hour urine specimens collected at the same intervals were assayed for PGI2 and TXA2 metabolites. In addition, bleeding time and platelet aggregation studies were performed prior to and after 7 days of LDA or placebo.


RESULTS
A dose-related increase in bleeding time occurred with 40 mg and 80 mg of LDA, but not with the 20 mg dose or placebo. Platelet aggregation studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA. The PGI2/TXA2 ratio increased with aspirin doses as low as 20mg, with a decrease in TXA2 metabolites but not in PGI2 metabolites. Serum salicylate was not detectable in any sample from any patient.


CONCLUSIONS
There are dose-related changes in platelet aggregation and bleeding times with progressively increasing doses of LDA. A lower dose of LDA, such as 20-40 mg per day, may be as efficacious as higher doses in the prophylaxis of pre-eclampsia in high risk populations.
Martin
C
C
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Varner
M W
MW
Branch
D W
DW
Rodgers
G
G
Mitchell
M D
MD
D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000652:urine*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D013928:Thromboxane A2 / Q000652:urine*
D013928:Thromboxane A2; D011464:Epoprostenol; D001241:Aspirin