Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder

Gris, Jean‐Christophe; Mercier, É.; Quéré, Isabelle; Lavigne-Lissalde, Géraldine; Cochery-Nouvellon, Éva; Hoffet, M.; Ripart-Neveu, Sylvie; Tailland, Marie-Laure; Dauzat, M.; Marès, P.

doi:10.1182/blood-2003-12-4250

Cited by 373 publications

(306 citation statements)

References 22 publications

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“…Thrombophilic conditions induced, in particular, FII and FV genes mutations are a cause for ovarian hyperstimulation syndrome [22]. Wherein the development of thrombophilic states may be minimized in advance by the therapy with preventive doses of thrombolytics, such as low molecular weight heparin, enoxaparin, or aspirin [23,24]. It is for these reasons FII and FV genes mutations are the first priority in SNP analysis panel presented.…”

Section: Snp In Blood Coagulation Factors Genes Which Were Included Imentioning

confidence: 99%

Toward optimal set of single nucleotide polymorphism investigation before IVF

Ivanov

Dedul

Fedotov

et al. 2016

Gynecological Endocrinology

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Background: At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP. Materials and methods: During 2009-2015 in the University Hospital of St. Petersburg State University, blood samples were analyzed from 550 women with different reproductive system disorders preparing for IVF and 46 healthy women in control group. In total, 28 SNP were analyzed in the genes of thrombophilia factors, folic acid cycle, detoxification system, and the renin-angiotensin system. The method used was real-time PCR. Results: A significant increase in the frequency of pathological alleles of some polymorphisms in patients with habitual failure of IVF was shown, compared with the control group. As a result, two options defined panels for optimal typing SNP before IVF were composed. Standard panel includes 8 SNP, 5 in thromborhilic factors, and 3 in folic acid cycle genes. They are 20210 G4A of FII gene, R506Q G4A of FV gene (mutation Leiden), -675 5G44G of PAI-I gene, L33P T4C of ITGB3 gene, -455 G4A of FGB gene, 667 C4T of MTHFR gene, 2756 A4G of MTR gene, and 66 A4G of MTRR gene. Extended panel of 15 SNP also includes 807 C4T of ITGA2 gene, T154M C4T of GP1BA gene, second polymorphism 1298 A4C in MTHFR gene, polymorphisms of the renin-angiotensin gene AGT M235T T4C and -1166 A4C of AGTR1 gene, polymorphisms I105V A4G and A114V C4T of detoxification system gene GSTP. Conclusion:The results of SNP genotyping can be adjusted for treatment tactics and IVF, and also medical support getting pregnant. The success rate of IVF is increased as the result, especially in the group with the usual failure of IVF.

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Section: Snp In Blood Coagulation Factors Genes Which Were Included Imentioning

confidence: 99%

Toward optimal set of single nucleotide polymorphism investigation before IVF

Ivanov

Dedul

Fedotov

et al. 2016

Gynecological Endocrinology

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“…LMWH has significant beneficial effects on trophoblast in vitro [10]. There is evidence of efficacy of LMWH in pregnancy loss not only with APAS but also from an important randomized trial of low-dose aspirin vs. enoxaparin in women with a history of pregnancy loss and associated Protein C deficiency, Protein S deficiency or Factor V Leiden [11]. When coupled with the substantial observational and trial data such as those from Brenner's group [1,12], which is the best evidence we have at present, and the difficulties of conducting randomized controlled trials in this patient group [13], this represents a significant body of data.…”

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confidence: 99%

“…Whether low-dose aspirin, which appears safe in pregnancy [8], should be added to LMWH in this situation is controversial. The combination appears effective in APAS, but the one randomized trial on pregnancy loss and heritable thrombophilia suggests that LMWH may be effective alone [11].…”

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confidence: 99%

The use of LMWH in pregnancies at risk: new evidence or perception?

Greer

2005

Journal of Thrombosis and Haemostasis

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“…Now, 1 year later, another forum on lower-molecular-weight heparin (LMWH) prophylaxis has been opened following a recent publication of Brenner et al Since the first debate, an important prospective study has been published supporting the use of LMWH. Gris et al [11] documented the superiority of LMWH when compared with aspirin in the prevention of fetal loss in women with a thrombophilic defect after a first pregnancy loss. Although this report did not deal with recurrent pregnancy loss, the study further supports the benefit of LMWH in women at risk.…”

mentioning

confidence: 99%

“…Gris et al [11] documented the superiority of LMWH when compared with aspirin in the prevention of fetal loss in women with a thrombophilic defect after a first pregnancy loss. Although this report did not deal with recurrent pregnancy loss, the study further supports the benefit of LMWH in women at risk.…”

mentioning

confidence: 99%

The use of LMWH in pregnancies at risk: new evidence or perception?

Zotz¹,

Gerhardt²,

Scharf³

2005

Journal of Thrombosis and Haemostasis

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The debate goes on. Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications is controversially discussed. In the October 2003 issue of the Journal of Thrombosis and Haemostasis, Middeldorp argued against the implementation of a Ôpotential harmful therapyÕ in women with hereditary thrombophilia and a history of recurrent pregnancy loss [1]. In the same issue, Brenner argued in favor of a heparin prophylaxis, based on the results of the limited number of studies available [2]. A forum on the subject in the July 2004 issue reflected the controversial positions [3][4][5][6][7]. Now, 1 year later, another forum on lower-molecular-weight heparin (LMWH) prophylaxis has been opened following a recent publication of Brenner et al. Since the first debate, an important prospective study has been published supporting the use of LMWH. Gris et al. [11] documented the superiority of LMWH when compared with aspirin in the prevention of fetal loss in women with a thrombophilic defect after a first pregnancy loss. Although this report did not deal with recurrent pregnancy loss, the study further supports the benefit of LMWH in women at risk. The recent trial by Brenner et al., comparing enoxaparin 40 and 80 mg day )1 , showed no significant difference in clinical outcome, indicating that the maximum effect of heparin treatment is already obtained with 40 mg day )1 [8]. A limitation of Brenner's study is the lack of a control group without heparin prophylaxis. Therefore, no validated conclusion on a treatment effect can be drawn.Although data in favor of LMWH are increasing, there are only a limited number of studies supporting heparin prophylaxis in women with recurrent pregnancy loss. Most of these studies are of low quality because of their historic controls. Although LMWH is widely used in pregnancy for prophylaxis of venous thromboembolism and although relevant adverse reactions are rare [12], its application in women with fetal loss requires thorough information on the risk-benefit ratio.There is much discussion on the impact of thrombophilic factors as risk determinants of pregnancy complications including recurrent pregnancy loss or pre-eclampsia [10]. In contrast to venous thromboembolism, the data are more conflicting, particularly in women with early fetal loss. We agree with Lindqvist et al. who, in their recent comment, question the validity of meta-analyses on this issue [10]. These meta-analyses are based on small retrospective studies, which are subject to a publication bias. More importantly, study results are likely to be biased by the increasing referral of women with predetermined thrombophilia to centers which enroll these patients in case-control studies. In consequence, the resulting odds ratio of thrombophilia is overestimated and reflects primarily a referral bias. As the placenta becomes the essential source of blood supply to the embryo between 8 and 10 weeks of gestation [9,13], early and late fetal loss must be separately evaluated and the enrollment of patients has to be ca...

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Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder

Cited by 373 publications

References 22 publications

Toward optimal set of single nucleotide polymorphism investigation before IVF

Toward optimal set of single nucleotide polymorphism investigation before IVF

The use of LMWH in pregnancies at risk: new evidence or perception?

The use of LMWH in pregnancies at risk: new evidence or perception?

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