Inherited Thrombophilia is Associated With Pregnancy Losses That Occur After 12th Gestational Week in Serbian Population

Mitić, Gorana; Kovač, Mirjana; Povazan, Ljubica; Magić, Zvonko; Djordjević, Valentina; Salatic, Iva; Mitić, Igor; Novakov-Mikic, Aleksandra

doi:10.1177/1076029609335518

Cited by 18 publications

(21 citation statements)

References 19 publications

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“…However, the MTHFR 677TT genotype is identified as a high genetic risk factor for recurrent SA, together with the homozygous 5G/5G polymorphism of the PAI-1gene in a Turkish population (Yenicesu et al, 2009). In agreement with this and also with the present study's findings, the homozygous MTHFR 677TT genotype was found with an increased frequency in recurrent SA patients in a Serbian population (Mitic et al, 2010).…”

Section: Disscussionsupporting

confidence: 91%

“…Numerous studies focus on the mechanism through which hyperhomocysteinemia, hereditary trombophilia (such as protein C or protein S deficiency, the factor V Leiden mutation, the prothrombin G20210A mutation) or combinations of these factors, could influence the normal in utero development and even play a role in spontaneous abortion etiology. Some authors suggest that as many as 60% of pregnancy losses could have been provoked by coagulation disorders (Bick and Hoppensteadt, 2005;Mitic et al, 2010). However, these conclusions are often inconsistent and results are contradictory (Altomare et al, 2007;Robertson et al, 2005;Rodger et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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The C677T Variant in the Methylenetetrahydrofolate Reductase Gene and Idiopathic Spontaneous Abortion in a Romanian Population Group

et al. 2012

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Spontaneous abortions (SA) are a major public health problem and a frequent pregnancy associated disorder. Hereditary thrombophilia and hyperhomocysteinemia are considered to be important factors altering the placental circulation, the in utero development and the evolution of pregnancy. The MTHFR gene (methylenetetrahydrofolate reductase) exhibits an intensely studied polymorphism, C677T, that was repeatedly associated with hyperhomocysteinemia, increased thrombotic risk and was studied in relation with SA susceptibility. This study was aim to assessing the correlation of this polymorphism with idiopathic sporadic or recurrent SA in a Romanian population. In the case-control study, 131 patients with a history of SA and 135 women with no SA and at least one uneventful term delivery were included. The PCR-RFLP technique (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) was used to genotype the cases and controls and the results were analysed using the χ 2 test. The present analysis indicates that the MTHFR 677TT homozygous genotype is positively associated with recurrent idiopathic SA (OR 2.493, 95%CI 0.974, 6.379, p-value 0.06). This association was no longer observed in sporadic SA patients (OR 1.214, 95%CI 0.488, 3.017, p-value 0.814). In conclusion, the present study is consistent with previous reports which state that the presence of MTHFR 677T variant in homozygous status could represent a genetic susceptibility factor for recurrent idiopathic SA. Moreover, this is the first attempt to investigate this correlation in a Romanian group and to offer epidemiological support in estimating the frequencies of some common genetic variants in the Romanian population.

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Section: Disscussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The C677T Variant in the Methylenetetrahydrofolate Reductase Gene and Idiopathic Spontaneous Abortion in a Romanian Population Group

et al. 2012

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“…In our population, we have also found an increased incidence of thrombophilic abnormalities in women with recurrent pregnancy loss, particularly if these occur after the 12 th gestational week (63,64). Results of the implementation of thromboprophylaxis in these women during subsequent pregnancies are encouraging, particularly for the most frequently found thrombophilias, such as FV Leiden and prothrombin gene mutation G20210A.…”

Section: Pregnancysupporting

confidence: 56%

An Integrative Approach to the Patient with Thrombophilia / SVEOBUHVATNI PRISTUP BOLESNIKU SA TROMBOFILIJOM

Mitić¹

2014

Journal of Medical Biochemistry

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SummaryVenous thromboembolism (VTE) is a multifactorial disease that results from a conjunction of several risk factors, both inherited and acquired. The younger the person, the more risk factors are required to cause the disease. Since 1937, when the term thrombophilia was coined by Nygaard and Brown, and 1965 when it was used for the first time by Egeberg, a substantial increase in the percentage of patients with VTE and underlying thrombophilia has been reported, particularly after the discovery of the most common thrombophilic mutations, FV Leiden and FII G20210A. Presence of thrombophilia could be detected in as many as 50% of all patients with VTE. Thrombophilia testing has increased lately not only in patients with thromboses but also for other indications, however, whether the results will help in the clinical management of the patients is still unclear. Thrombo philia testing is most commonly performed in young patients with VTE, patients with recurrent episodes of VTE or with thromboses at unusual sites and in persons with positive family history. Whether the presence of thrombophilia influences the clinical management of the patient remains controversial. Patients with VTE and the recognized risk factors such are surgery, trauma, immobilization, pregnancy and the puerperium are at very low risk for recurrence, but prediction of the recurrence of VTE based on the presence of thrombophilia has not been sufficiently explored. Presence of clinical risk factors should be integrated in the strategy of VTE risk assessment. Since many risk factors, such as obesity, hypertension, dyslipidemia, diabetes and smoking are common for both arterial and venous thromboses, it has been suggested that VTE should be considered as part of a pancardiovascular syndrome, along with coronary artery disease, Kratak sadr`ajVenska tromboembolijska bolest (VTE) nastaje kao rezultat udru`enog delovanja brojnih faktora rizika, kako naslednih tako i ste~enih. U~estalost VTE je direktno povezana sa staro{}u, tako da je u mla|em uzrastu neophodno udru`eno delovanje vi{e faktora rizika za nastanak venske tromboze. Prisustvo trombofilije se mo`e utvrditi kod oko polovine bolesnika sa VTE. Dijagnostika trombofilije je sve ~e{}a u svako dnevnom laboratorijskom radu, ne samo kod bo lesnika sa trombozama ve} i za druge indikacije kao {to su komplikacije trudno}e izazvane o{te}enjem placentalne vasku larizacije, a da nije u potpunosti razja{njeno da li }e prisustvo trombofilije uticati na dalji tok le~enja i sveobuhvatni pristup bolesniku. Naj~e{}e indikacije za ispitivanje trombofilije su tromboze u mla |em uzrastu, recidivi venskih tromboza, tromboze na ne uo bi~ajenim mestima kao i postojanje tromboza kod vi{e ~la no va porodice. Dijagnostika trombofilije se naje{}e ko risti kao pomo} u proceni rizika za nastanak recidiva VTE, mada je dosada{njim ispitivanjima pokazano da samo te{ke trom bo filije, kao {to su deficit inhibitora koagulacije, homo zigotni oblik mutacije FV Leiden ili udru`eni heterozigoti za FV Lei den i FII G20210A, predst...

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“…Among five studies (conducted in Israel, 95,100,110 Serbia, 80 and Spain 54 ), a phenotypic test, APCR, was used to determine which women would be tested for the F5 variant. The remaining 37 studies genotyped all women.…”

Section: Case-control Studiesmentioning

confidence: 99%

“…72 Pihusch 89 Many 78 Foka 63 Mitic 80 Souza 98 Sottilotta 97 Kupferminc 112 Hohlagschwandtner 69 Reznikoff-Etievant 92 …”

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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Inherited Thrombophilia is Associated With Pregnancy Losses That Occur After 12th Gestational Week in Serbian Population

Cited by 18 publications

References 19 publications

The C677T Variant in the Methylenetetrahydrofolate Reductase Gene and Idiopathic Spontaneous Abortion in a Romanian Population Group

The C677T Variant in the Methylenetetrahydrofolate Reductase Gene and Idiopathic Spontaneous Abortion in a Romanian Population Group

An Integrative Approach to the Patient with Thrombophilia / SVEOBUHVATNI PRISTUP BOLESNIKU SA TROMBOFILIJOM

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

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