Meta-analysis on aspirin combined with low-molecular-weight heparin for improving the live birth rate in patients with antiphospholipid syndrome and its correlation with d-dimer levels

Abstract Abstract 488 Background Unexplained recurrent miscarriage (RM) is extremely stressful for women and effective treatment is eagerly awaited. Aspirin and (low-molecular-weight) heparin are being used increasingly, even though evidence to support its use is not availabel. The aim of the ALIFE study was to investigate whether aspirin alone or combined with low-molecular-weight heparin, compared to placebo, improved the live birth rate in women with unexplained RM. Methods We conducted a multicenter, randomized, controlled trial in 8 centers in The Netherlands. Women aged between 18 and 42 years were eligible if they were diagnosed with unexplained RM and attempted to conceive or were less than 6 weeks pregnant. RM was defined as at least 2 miscarriages with an upper gestational age of 20 weeks (calculated from the first day of the last menstrual period). Unexplained RM was diagnosed in case of normal parental karyotype, the absence of uterine pathology on pelvic ultrasound, absence of antiphospholipid syndrome (lupus anticoagulant and anticardiolipin IgG and IgM), and a normal fasting level of homocysteine (< 16 μmol/L). Exclusion criteria were previous venous or arterial thromboembolism, indication for anticoagulant treatment during pregnancy or endocrine disorders. After written informed consent was obtained, randomization was performed centrally with stratification for age (< or ≥36 years), number of previous miscarriages (2 or ≥3), and center. Oral medication was started at the day of inclusion. Aspirin was given as calcium carbasalate 100 mg (Ascal®, Vemedia BV, Diemen, The Netherlands), equivalent to 80 mg of acetylsalicylic acid. Aspirin and placebo study medication was packed in sachets of identical appearance. Patients, doctors, and trial nurses were blinded for these treatment allocations. Women allocated to receive open-label nadroparin 2850 IU s.c. received oral aspirin and started nadroparin injections when a viable intrauterine pregnancy was confirmed by ultrasound from 6 weeks of gestational age. Aspirin or placebo was given until 36 weeks of gestational age or stopped at time of miscarriage, ectopic pregnancy or premature delivery. LMWH was given throughout gestation and stopped 12 hours before delivery. The primary outcome measure was live birth rate. Secondary outcomes included miscarriage rate, uterine and umbilical blood flow profile and prevalence of obstetric complications. Differences in live birth rates will be expressed as relative risks and 95% confidence intervals with the placebo group as reference. Data were analyzed according to the intention-to-treat principle. Preliminary results Between February 2004 and January 2008, 364 women were included in the trial. On July 1st 2009, 25 were not pregnant 2 years after inclusion, 16 were not pregnant, 8 were pregnant, 26 women had decided to withdraw from the study, and 3 had been included erroneously. The results presented in this abstract are based on a pre-scheduled interim analysis of 281 women who had reached an endpoint (live birth or miscarriage) on July 1st 2009. The live birth rate did not differ between women assigned to aspirin, aspirin combined with nadroparin, and placebo. The Data Safety Monitoring Board advised the Steering Committee of the ALIFE study that further continuation of the study was futile. At the time of submission of this abstract, the database is being finalized, with closure scheduled on October 1st 2009. We will present definite data, including those of the a priori defined subgroup of women with hereditary thrombophilia, at the ASH meeting in December 2009. Conclusions Aspirin, and aspirin combined with nadroparin did not improve the live birth rate in women with unexplained RM (Current Controlled Trial number, ISRCTN58496168). Funding: ZonMW, the Dutch Organization for Health Research and Development (945-27-003). Vemedia BV supplied study medication (calcium carbasalate and placebo). GlaxoSmithKline BV offered a grant. Funding sources were not involved in study protocol preparation, trial management or data analysis. Disclosures: Off Label Use: Calcium carbasalate (equivalent to acetyl salicylic acid) and nadroparin to prevent recurrent miscarriage.. Buller:GSK: Consultancy, Honoraria, Research Funding. Middeldorp:GSK: Consultancy, Honoraria, Research Funding.

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Low-molecular-weight heparin plus aspirin versus aspirin alone in pregnant women with hereditary thrombophilia to improve live birth rate: meta-analysis of randomized controlled trials

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-015-3782-2 ◽

2015 ◽

Vol 293 (1) ◽

pp. 81-86 ◽

Cited By ~ 6

Author(s):

Ana Luísa Areia ◽

Etelvina Fonseca ◽

Miguel Areia ◽

Paulo Moura

Keyword(s):

Molecular Weight ◽

Randomized Controlled Trials ◽

Pregnant Women ◽

Low Molecular Weight Heparin ◽

Birth Rate ◽

Meta Analysis ◽

Live Birth Rate ◽

Controlled Trials ◽

Low Molecular Weight ◽

Randomized Controlled

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Comparative study of low dose aspirin versus combination of low dose aspirin and low molecular weight heparin in idiopathic recurrent pregnancy loss

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20200010 ◽

2020 ◽

Vol 9 (2) ◽

pp. 512

Author(s):

S. Bhanu Rekha ◽

K. Sharath Chandra

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Pregnancy Loss ◽

Birth Rate ◽

Low Dose ◽

Recurrent Pregnancy Loss ◽

Live Birth Rate ◽

Low Molecular Weight ◽

Dose Aspirin ◽

Low Dose Aspirin

Background: To compare the role of low dose aspirin versus combination of low dose aspirin and low molecular weight heparin in idiopathic recurrent pregnancy loss and assess the effectiveness of low dose aspirin and low molecular weight heparin in having a better obstetric outcome.Methods: This study was conducted in a private hospital in Mahabubnagar from June 2017 to May 2019. A total of 80 pregnant ladies who had previous 2 and or more pregnancy losses in the early (before 20 weeks) or late (after 20 weeks) pregnancy period was included in the study. 80 pregnant women with idiopathic/unexplained recurrent pregnancy loss were properly evaluated in regard to the history of previous period of gestation of loss, previous scans in regard to documentation of fetal pole and gestation, cardiac activity, anomaly scan and growth scan and any special investigations in previous pregnancies and present pregnancy.Results: A total 80 pregnant women with previous 2 and more unexplained pregnancy losses who were evaluated and found negative with major causes of pregnancy losses half of them (40) were treated with low dose aspirin alone and the other 40 women were treated with a combination of low dose aspirin (75 mg) and low molecular weight Heparin (20 mg) daily low molecular weight heparin till term. The aspirin alone group had 82.5% live birth rate and the combination group had 92.5% live birth rate which is quite satisfactory and more than the Aspirin alone group.Conclusions: Use of combination of low dose aspirin and low molecular weight heparin seems to be a good choice of drugs in treating the unexplained recurrent pregnancy losses than low dose aspirin alone.

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Natural Course of the Subsequent Pregnancy after a Single Loss in Women with and without the Factor V Leiden or Prothrombin 20210A Mutations.

Blood ◽

10.1182/blood.v108.11.275.275 ◽

2006 ◽

Vol 108 (11) ◽

pp. 275-275 ◽

Cited By ~ 5

Author(s):

Michiel Coppens ◽

Nienke Folkeringa ◽

Margreet Teune ◽

Karly Hamulyak ◽

Jan van der Meer ◽

...

Keyword(s):

Live Birth ◽

Low Molecular Weight Heparin ◽

Pregnancy Loss ◽

Birth Rate ◽

Factor V Leiden ◽

Late Pregnancy ◽

Live Birth Rate ◽

Low Molecular Weight ◽

Factor V ◽

Prothrombin 20210A

Abstract In previous case control studies factor V Leiden and the prothrombin 20210A mutation have been associated with pregnancy loss, in particular recurrent and late (>12 weeks of gestation) losses in women carriers1. The prognosis of a second pregnancy after an initial late pregnancy loss in women with inherited thrombophilia is uncertain; the live birth rate reported in different cohort studies varied from 11 to 98%2–4. This has led to a debate about whether low-molecular-weight heparin should be prescribed to women with thrombophilia and pregnancy loss, despite the absence of evidence about its effectiveness from placebo-controlled trials. We determined the live birth rate of the 2nd pregnancy following a first loss in a large family study that included patients with documented venous thromboembolism or premature atherosclerosis and carriership of the factor V Leiden or prothrombin 20210A mutations and their 1st degree relatives. Ectopic or terminated pregnancies and pregnancies lost due to known chromosomal abnormalities were excluded, as well as pregnancies during which anticoagulants were used. A total of 993 women (498 carriers) who had had 2809 pregnancies (1420 in carriers) were analyzed. After an early pregnancy loss in the 1st pregnancy, the live birth rate of the 2nd pregnancy was 77% (95%CI 62–87) in carriers and 76% (95%CI 57–89) in non-carriers. After a late pregnancy loss in the 1st pregnancy, the live birth rate of the 2nd pregnancy was 68% (95%CI 46–85) in carriers and 80% (95%CI 49–94) in non-carriers (OR 0.9, 95%CI 0.5–1.3). We conclude that the pregnancy outcome in women with either factor V Leiden or the prothrombin 20210A mutation is fairly similar to the outcome in women without these mutations. After a late pregnancy loss in the first pregnancy, the live birth rate in the second pregnancy tended to be somewhat lower for carriers than for non-carriers. The live birth rates for both carriers and non-carriers in this study was substantially higher than in some other cohorts, which may be due to the fact that the cohort was not selected based on obstetric indications. Given the observed favourable prognosis after a first pregnancy loss even in women with known thrombophilia and a late loss, low-molecular-weight heparin to improve pregnancy outcome should not be used before results from ongoing randomized placebo controlled trials have shown its effectiveness and safety.

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Risikoschwangerschaften und deren Therapie

Hämostaseologie ◽

10.1055/s-0037-1619784 ◽

2012 ◽

Vol 32 (S 01) ◽

pp. S90-S94 ◽

Cited By ~ 1

Author(s):

H. Radtke ◽

R. Becker ◽

F. P. Schmidt ◽

K. Körber ◽

N. Vehlow ◽

...

Keyword(s):

Live Birth ◽

Low Molecular Weight Heparin ◽

Birth Rate ◽

Live Birth Rate ◽

Low Molecular Weight ◽

Target Variable ◽

Vein Thrombosis ◽

Live Birth Rates ◽

Recurrent Abortions ◽

Deep Vein

SummaryRecurrent abortions are a common problem. A therapy with low-molecular-weight heparin is usual in deep vein thrombosis with thrombophilia, in woman with recurrent abortions or other risks, like EPH-gestosis or HELLP-Syndrom. Patients, method: The efficacy of a mono-therapy with LMWH (3000–16 000 daily) in women with risk pregnancies has been examined prospectively. The dates of 676 pregnant women have been analysed and compared to the current literature about live birth rates without therapy and tot he results of other, similar studies. The live birth rate has been the target variable. Results: We obtained main a live birth rate of 98.6%.There has been no record of serious adverse effects. We obtained a live birth rate of 95.8% if NMH therapy starts early, and a live birth rate of 100% if NMH therapy starts between week 20 and 25. For the live birth rate the existence of thrombophilic gene polymorphisms is irrelevant. Conclusion: The high live birth weight is depended on early starting the therapy with NMH. For the late risk it is favourable to start the therapy with heparin between week 20 and 25 week of pregnancy.

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