Dose-related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy

Abstract

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.

Conclusion: 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.