DOSE-RELATED EFFECTS OF LOW-DOSE ASPIRIN ON HEMOSTASIS PARAMETERS ANDPROSTACYCLIN 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 (PGI(2))/ thromboxane (TXA(2)) ratio and minimized evidence of platelet aggregat ion during normal late pregnancy. Methods: Twelve women with uncomplic ated singleton pregnancies between 28 and 34 weeks gestation participa ted in a randomized blinded study. Blood samples for salicylate levels were obtained pre treatment, 4 hours and 7 days after administration of placebo, 20mg, 40mg or 80mg of aspirin. Twenty-four hour urine spec imens collected at the same intervals were assayed for PGI(2) and TXA( 2) metabolites. In addition, bleeding time and platelet aggregation st udies were performed prior to and after 7 days of LDA or placebo. Resu lts: 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 aggrega tion studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA. The PGI(2)/TXA(2) ratio increased with aspirin doses as low as 20mg, with a decrease in TXA(2) metabolites b ut not in PGI(2) metabolites. Serum salicylate was not detectable in a ny sample from any patient. Conclusion: There are dose-related changes in platelet aggregation and bleeding rimes with progressively increas ing doses of LDA. A lower dose of LDA, such as 20-40 mg per day, may b e as efficacious as higher doses in the prophylaxis of pre-eclampsia i n high risk populations.