Effect of low-dose aspirin during pregnancy on fibrinolytic variables before and after parturition.

OBJECTIVE: We assessed the effects of a daily oral dose of 60 to 80 mg of aspirin from 12 weeks' gestation until delivery on fibrinolytic variables before and after parturition. STUDY DESIGN: In a prospective controlled study labor was electively induced in 24 patients, eight receiving low-dose aspirin and 16 controls. Levels were determined in maternal and cord plasma of tissue-type plasminogen activator antigen and activity, plasminogen activator inhibitor-1 antigen, plasminogen activator inhibitor activity, and plasminogen activator inhibitor-2 antigen. We also determined metabolites of vascular prostacyclin and platelet thromboxane A2. RESULTS: The only maternal fibrinolytic variable affected by low-dose aspirin was plasminogen activator inhibitor activity, which showed a significant reduction before and after parturition of 40% and 70%, respectively, in low-dose aspirin users compared with controls. Concentrations of thromboxane B2 in women using low-dose aspirin were 7% (maternal serum) and 17% (cord serum) of values in controls, but concentrations of 6-keto-prostaglandin F1 alpha were not affected. CONCLUSIONS: Low-dose aspirin reduces plasminogen activator inhibitor activity and platelet reactivity, but not prostacyclin synthesis, before and after parturition. The reduction in plasminogen activator inhibitor activity may be caused by inhibition of platelet reactivity.

Effect of low-dose aspirin on vascular refractoriness in angiotensin-sensitive primigravid women.

The hypothesis that an enhanced vasopressor response to angiotensin II in pregnancy may be corrected by suppressing production of platelet thromboxane A2 with low-dose aspirin was tested in a randomized, placebo-controlled, double-blind trial. We studied 36 normotensive primigravid women with an elevated blood pressure response to intravenously infused angiotensin II at 28 weeks' gestation; 18 women received 60 mg of aspirin daily and the same number received matched placebo until 34 weeks' gestation, when angiotensin-sensitivity was again determined. In women taking aspirin, values of thrombin-induced platelet malondialdehyde production were approximately 10% of those determined in the placebo group, indicating marked suppression of thromboxane A2 synthesis. In the aspirin group vascular refractoriness to angiotensin II was restored in 14 of 17 treated women, by comparison with 5 of 15 women in the placebo group who had remained normotensive. These results support the hypothesis that prostacyclin/thromboxane imbalance is an important pathophysiologic factor in the development of the enhanced angiotensin-sensitivity associated with pregnancy-induced hypertensive disorders.

Prevention of recurrent idiopathic fetal growth retardation by low-dose aspirin and dipyridamole.

In a controlled, nonrandomized trial a treatment group of 24 multigravid women with a history of at least two previous pregnancies, all complicated by idiopathic fetal growth retardation and placental infarction, received 1 to 1.6 mg/kg aspirin and 225 mg dipyridamole daily from 16 to 34 weeks' gestation in a total of 30 pregnancies. The end-point measure of the study was birth weight related to gestational age. Results obtained in the treatment group were compared with those in 27 pregnancies of a control group of 24 multigravid women with a similar history of recurrent fetal growth retardation who received comparable antenatal care without low dose aspirin and dipyridamole. Fetal growth retardation occurred in 61% of the control pregnancies and in only 13% of treated pregnancies; severe fetal growth retardation was not observed in treated pregnancies, but it occurred in 27% of the control group. In treated women, platelet cyclo-oxygenase activity was suppressed to 5% to 10% of its pretreatment level, but no effect on vascular prostacyclin production was demonstrated. Treatment did not produce adverse effects in mothers or infants. Low-dose aspirin and dipyridamole direct prostacyclin/thromboxane A2 balance in pregnancy to the dominance of prostacyclin and may thus prevent idiopathic uteroplacental insufficiency and fetal growth retardation in high-risk patients.

Enhanced reactivity of the platelet thromboxane pathway in normotensive and hypertensive pregnancies with insufficient fetal growth.

The reactivity of the platelet thromboxane pathway was investigated by means of measurement of thrombin-induced formation of malondialdehyde in platelets obtained from 26 women in the third trimester of uncomplicated pregnancies, 27 patients with normotensive pregnancies who were delivered of small--for--gestational age infants, 27 patients with pregnancy-induced hypertension and infants with normal birth weights, and 20 patients with pregnancy-induced hypertension and small--for--gestational age infants. Platelet life span and distribution of platelet volumes were also determined. In normotensive and hypertensive pregnant women with small--for--gestational age infants, platelet malondialdehyde formation was significantly increased, and platelet life span was reduced as compared with the other groups. The enhanced reactivity of the platelet thromboxane pathway may be expected to contribute to the increased in vivo platelet activation and consumption which occur in pregnancies with chronic placental insufficiency. Deficient production of placental vascular prostacyclin might be the underlying cause.