thromboxane-a2 and Abortion--Habitual

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis in essential thrombocythemia (ET) has become an important issue. The rationale for its use in ET comes from the observation that arterial thrombosis and platelet-mediated microcirculatory disturbances are the major causes of morbidity and mortality in ET. Experimental data have shown persistently elevated levels of thromboxane A2 (TXA2) in ET patients probably reflecting an enhanced in vivo platelet activation. Increased TXA2 biosynthesis and platelet activation in vivo in ET are selectively suppressed by repeated low doses of aspirin. ET-related symptoms such as erythromelalgia, transient neurologic and ocular disturbances are sensitive to aspirin. However, the benefit of low-dose aspirin is still uncertain in the primary prevention of thrombosis in ET. Furthermore, aspirin may unmask a latent bleeding diathesis frequently present in ET which may result in severe hemorrhagic complications. Thus, aspirin is contraindicated in ET patients with a bleeding history or a very high platelet count (> 1500 x 10(9)/L) leading to the acquisition of von Willebrand factor deficiency. If indicated, aspirin is presently used in the widely accepted low-dose regimen of 100 mg daily. However, an optimal effective dose has not yet been established. To further evaluate the efficacy and safety of aspirin in ET, prospective clinical trials are needed.

Topics: Abortion, Habitual; Aspirin; Cerebrovascular Disorders; Cohort Studies; Contraindications; Erythromelalgia; Female; Fibrinolytic Agents; Forecasting; Hemorrhage; Humans; Incidence; Middle Aged; Myeloproliferative Disorders; Pilot Projects; Platelet Activation; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Hematologic; Retrospective Studies; Safety; Thrombocythemia, Essential; Thrombophilia; Thrombosis; Thromboxane A2; Vision Disorders; von Willebrand Diseases

All pregnancy-associated tissues are capable of producing prostaglandins including PGI2 and TXA2. In normal pregnancy there is a dominance of PGI2 over TXA2 which may contribute to the maternal circulatory adaptation to pregnancy. Furthermore, both fetoplacental PGI2 and TXA2 production are important regulators of the fetal blood supply. It has been clearly established that in pre-eclampsia PGI2 production decreases in the fetoplacental tissues and quite probably also in the maternal tissues. The effect of this change may be further exaggerated by the simultaneous stimulation in pre-eclampsia of TXA2 production. The reason for PGI2 deficiency is not known. Other vasoactive agents, such as endothelin, may act in concert with prostaglandins. Relative PGI2 deficiency is likely to exist also in IUGR and lupus anticoagulant syndrome of pregnancy. In the latter, lupus anticoagulant may directly inhibit the synthesis of PGI2. One study suggests PGI2 deficiency also in early pregnancies of women with a history of repeated abortions. Prostaglandin production increases during full-term labour, and similar but smaller changes also occur in preterm labour. A silent bacterial infection may trigger the onset of preterm labour through cytokine-stimulated increase of prostaglandin production. No data were found on prostaglandin production in post-term pregnancies. That oligo-polyhydramnios is possibly prostaglandin mediated is suggested by the control of polyhydramnios by indomethacin treatment. Smoking decreases the production of PGI2 and possibly increases that of TXA2, which may lead to decreased blood flow and IUGR. Which constituent of cigarette smoke exerts this effect is not known. Ethanol consumption causes aberrations in prostaglandin metabolism which cannot be directly connected with fetal alcohol effects.

Topics: Abortion, Habitual; Alcohol Drinking; Epoprostenol; Female; Fetal Growth Retardation; Humans; Lupus Erythematosus, Systemic; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prostaglandins; Smoking; Thromboxane A2; Thromboxane B2

Recurrent miscarriage is a major women's health problem. Aspirin and heparin have been shown to have potentially beneficial effects on trophoblast implantation. However, few published data on this issue are available from developing countries.. An open clinical trial was conducted at the Department of Obstetrics and Gynecology at Misurata Teaching Hospital in Libya from January 2009 to December 2010 to investigate the effects of treatment with low dose aspirin (LDA) versus treatment with low-molecular-weight-heparin (LMWH) in combination with LDA on patients with a history of recurrent miscarriages. A total of 150 women were enrolled in the study. Women were eligible for the study if they had a history of three or more consecutive miscarriages. Participants were randomly assigned to receive either LDA (75 mg daily) alone or a combination of LDA and LMWH (75 women per treatment group). The primary outcomes were the rate of miscarriages and live births for each group.. Compared with the group who received LDA alone, the combination group had a significantly lower number of miscarriages (22/75 [29%] vs. 43/75 [47%], P < 0.001) and had a significantly higher number of live births (53/75 [71%] vs. 32/75 [42%], P < 0.001). Two preterm infants in the LDA group and three in the combination group were admitted to the neonatal intensive care unit. There were no significant differences in the mean (SD) birth weights of neonates born in either group (2955.4 ± 560 vs. 3050 ± 540 g for the LDA and combination groups, respectively, P = 0.444). There were no congenital abnormalities detected in either group.. The combination of LDA and LMWH is better than LDA alone for the maintenance of pregnancy in patients with recurrent first trimester miscarriage.. NCT01917799.

Topics: Abortion, Habitual; Adult; Aspirin; Birth Weight; Embryo Implantation; Enoxaparin; Female; Fibrinolytic Agents; Humans; Infant, Newborn; Libya; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Prostaglandins I; Thrombophilia; Thromboxane A2; Trophoblasts; Vasodilation; Young Adult

Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.

Topics: Abortion, Habitual; Adult; Aspirin; Autoimmune Diseases; Blood Platelets; Epoprostenol; Female; Humans; Pregnancy; Thromboxane A2; Thromboxane B2

To see if changes in prostacyclin and thromboxane A2 (TXA2) production during early pregnancy in women with habitual abortion is a pregnancy-induced change, we compared the production of these prostanoids in habitual aborters and in healthy controls in nonpregnant state and related it to luteal function.. Comparison between patients (n = 16) with a history of at least three consecutive miscarriages and healthy controls without a history of abortions (n = 11).. Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland.. Habitual aborters and control women exhibited no change in the urinary output of the stable degradation products of prostacyclin and TXA2 when studied between 0 and 2 and 5 and 8 days after the luteinizing hormone peak. Habitual aborters as a whole, or when subgrouped to those with normal (10 cycles) or defective luteal function (12 cycles) did not differ from the control series with regard to prostacyclin and TXA2 production.. Productions of prostacyclin and TXA2 are not relative to the luteal function and are normal in nonpregnant women with a history of habitual abortion.. To examine if changes in prostacyclin and thromboxane A2 (TXA2) production during early pregnancy in women with habitual abortion are pregnancy-induced the authors compared the production of these prostanoids in habitual aborters with those in healthy controls in a nonpregnant state and related it to luteal function. Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Finland, were the setting of this comparison between patients with a history of at least 3 consecutive miscarriages (n=16) and healthy controls without a history of abortions (n=11). Habitual aborters and control women exhibited no change in urinary output of the stable degradation products of prostacyclin and TXA2 when studied between 0 and 2 and 5 and 8 days after the luteinizing hormone peak. Habitual aborters as a whole, or when subgrouped to those with normal (10 cycles) or defective luteal function (12 cycles), did not differ from the control series with regard to prostacyclin and TXA2 production. Productions of prostacyclin and TXA2 are not relative to the luteal function and are normal in nonpregnant women with a history of habitual abortion.

Topics: Abortion, Habitual; Adult; Epoprostenol; Female; Humans; Luteal Phase; Medical Records; Pregnancy; Thromboxane A2

To evaluate the significance of vasoactive prostanoids in habitual abortion, we measured urinary excretion of prostacyclin metabolites (6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and of thromboxane A2 metabolites (TxB2 and 2,3-dinor-TxB2) during 25 pregnancies in 22 women with recurrent spontaneous abortion (RSA). The control group were 16 pregnant women with no history of abortion. Ultrasound examination at first follow-up appointment showed a living fetus in 23 pregnancies of women with RSA. 9 of these pregnancies ended in abortion; 14 continued to term as did all the pregnancies in the control group. Compared with controls, women with RSA had a lower (p less than 0.05) ratio of prostacyclin to thromboxane between weeks 4 and 7 of gestation and a lower (p less than 0.01) output of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11. Women whose pregnancies ended in abortion had higher (p less than 0.05) output of 2,3-dinor-TxB2 between weeks 4 and 7 of gestation and lower (p less than 0.01) excretion of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11 compared with women whose pregnancies proceeded to term. We conclude that deficiency of vasodilatory prostacyclin may be a factor in habitual abortion.

Topics: 6-Ketoprostaglandin F1 alpha; Abortion, Habitual; Epoprostenol; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Thromboxane A2; Thromboxane B2