Hypercoagulable Thrombophilic Defects and Hyperhomocysteinemia in Patients with Recurrent Pregnancy Loss

Raziel, Arieh; Kornberg, Y; Friedler, S.; Schächter, M; Sela, Ben Ami; Ron-El, Raphaël

doi:10.1111/j.8755-8920.2001.450201.x

Cited by 99 publications

(67 citation statements)

References 31 publications

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“…The risk of venous thrombo-embolism is increased seven to ten fold in patients with this deficiency. Two studies that examined the association between protein C deficiency and fetal loss, showed a non-significant association (Raziel et al, 2001;Gris et al, 1999).…”

Section: Protein C Deficiencymentioning

confidence: 99%

“…The homozygous form of the mutation induces a state of hyperhomocysteinaemia (Kujovic, 2004). Hyperhomocysteinaemia has a reported prevalence of around 5 % to 16 % in the general population (Kumar et al, 2003;Raziel et al, 2001). A meta-analysis reported a 3-to 4-fold increased risk of recurrent early pregnancy loss in women with hyperhomocysteinaemia ).…”

Section: Methylenetetrahydrofolate Reductase Deficiency and Hyperhomomentioning

confidence: 99%

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Inherited and Acquired Thrombophilia in Pregnancy

Dawood¹

2011

Thrombophilia

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Section: Protein C Deficiencymentioning

confidence: 99%

Section: Methylenetetrahydrofolate Reductase Deficiency and Hyperhomomentioning

confidence: 99%

Inherited and Acquired Thrombophilia in Pregnancy

Dawood¹

2011

Thrombophilia

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“…These data confirmed an effect for both F5 and F2 (P < 0.001). More importantly, there was con cern that the casecontrol data did not provide direct evidence 99 Foka 63 Onderoglu 86 Grandone 66 Brenner 57 Krause 75 Fatini 61 Raziel 91 Agorastos 50 Glueck 64 Sottilotta 97 Hohlagschwandtner 69 Reznikoff-Etievant 92 Souza 98 Ridker 93 Hopmeier 70 Many 78 Murphy 85 Ivanov 72 Sotiriadis 96 Metz 79 Pauer 88 …”

mentioning

confidence: 99%

Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review

Bradley

Palomaki

Bienstock

et al. 2012

Genetics in Medicine

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Women with recurrent pregnancy loss are offered Factor V Lei den (F5) and/or prothrombin G20210A (F2) testing to identify candidates for anticoagulation to improve outcomes. A systematic literature review was performed to estimate test performance, effect sizes, and treatment effectiveness. Electronic searches were per formed through April 2011, with review of references from includ ed articles. Englishlanguage studies addressed analytic validity, clinical validity, and/or clinical utility and satisfied predefined in clusion criteria. Adequate evidence showed high analytic sensitivity and specificity for F5 and F2 testing. Evidence for clinical validity was adequate. The summary odds ratio for association of recurrent pregnancy loss with F5 in casecontrolled studies was 2.02 (95% confidence interval, 1.60-2.55), with moderate heterogeneity and suggestion of publication bias. Longitudinal studies in women with recurrent pregnancy loss or unselected cohorts showed F5 carriers were more likely to have a subsequent loss than noncarriers (odds ratios: 1.93 and 2.03, respectively). Results for F2 testing were simi lar. For clinical utility, evidence was adequate that anticoagulation treatments were ineffective (except in antiphospholipid antibody syndrome) and had treatmentassociated harms. The certainty of evidence is moderate (high, moderate, and low) that anticoagula tion of women with recurrent pregnancy loss and F5/F2 variants would currently lead to net harms. Pregnancy loss is a common medical problem among repro ductive age women. 1 However, relatively few women having one pregnancy loss experience multiple or "recurrent" preg nancy losses (RPLs). Approximately 5% of such women experi ence a second pregnancy loss and only 1-2% three or more. Genet Med 1Evaluation for RPL often includes ruling out parental chro mosome abnormalities, identifying maternal exposures, and testing for underlying maternal conditions. 1,2 Effective clinical interventions are available for some etiologies, such as correct ing uterine anomalies surgically and treating antiphospholipid syndrome with aspirin and heparin. [3][4][5] The evidence review summarized herein addressed the asso ciation of inherited thrombophilia with RPL, focusing on tests for two genetic variants that are frequently ordered: Factor V Leiden ("F5") and prothrombin G20210A ("F2"). F5 defines a singlenucleotide substitution in the F5 gene (i.e., Factor V Leiden; F5 c.1691G>A; and p.Arg506Gln), 3,6 whereas F2 defines a singlenucleotide substitution in an untranslated region of the F2 gene (i.e., prothrombin G20210A and F2 c.20210G>A). 4,6 Associations between these (and other) heritable thrombo philia variants and serious pregnancy complications (e.g., RPL, fetal growth restriction, placental abruption, and preeclampsia) began to appear in the literature in 1996.6 By 2005, laborato ries were offering clinical testing for F5/F2 as part of "infertil ity" or RPL evaluations. 7 In some states, these tests continue to be available directly to consumers through the intern...

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“…One percent to 5% of pregnant women with recurrent abortions (RA) of which 40%-55% are induced by unknown causes (4)(5)(6). Known etiologic factors of RA are parental chromosome abnormalities, uterine abnormalities, hereditary thrombophilia, endocrinologic disorders, immunologic factors, infections, and nutritional and environmental factors (7).…”

Section: Introductionmentioning

confidence: 99%