Clinical variability of haemophilia A and B in Mexican families by factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T/A1298C

López‐Jiménez, José de Jesús; Beltrán-Miranda, Claudia Patricia; Mantilla-Capacho, Johanna Milena; Esparza-Flores, M. A.; Jaloma‐Cruz, Ana Rebeca

doi:10.1111/j.1365-2516.2009.02069.x

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…Several studies indicated that the MTHFR 677C>T polymorphism, especially in the homozygous state, could be associated with a milder clinical phenotype of hemophilia (Ahmed, Kannan, Choudhry, & Saxena, ; Ghosh, Shetty, & Mohanty, ; Nowak‐Göttl et al., ). However, our previous study did not reveal any attenuating effects of MTHFR 677C>T on the hemorrhagic phenotype in the presence of FV 1691G>A or FII 20210G>A (López‐Jiménez et al., ).…”

Section: Discussionmentioning

confidence: 73%

Genetic biomarkers related to hemarthrosis, inflammation, and cartilage structure in pediatric patients with hemophilic arthropathy

López‐Jiménez

Ortega‐Cervantes²,

Luna-Záizar³

et al. 2019

Molec Gen & Gen Med

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BackgroundThe pathophysiology of hemophilic arthropathy is complex and not completely understood. In this study, we aimed to identify biomarkers that can affect the hemophilic arthropathy severity.MethodsFifty patients were analyzed for biomarker frequencies; in 37 patients, articular symptoms were evaluated based on the physical joint examination score, and in 18, it was based on magnetic resonance imaging. Eight polymorphisms, namely FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, TNFα‐308G>A and ‐238G>A, ACAN VNTR, and IL1RN*2‐VNTR were identified.ResultsPatients with the MTHFR 677TT genotype showed a higher number of affected joints (1.83 ± 0.9 vs. 0.55 ± 0.7 for CC; p = .023), whereas those with the MTHFR 1298AC genotype exhibited higher effusion according to two radiologists (0.90 ± 0.31/1.20 ± 0.63 vs. 0.38 ± 0.52/0.50 ± 0.53 for AA genotype; p = .043/0.036, respectively). In addition, patients with the TNFα‐308GA genotype had more subchondral cysts (0.75 ± 0.95 vs. 0.07 ± 0.26 for GG genotype; p = .041).ConclusionsThe distribution of risk genotypes for MTHFR and TNFα‐308GA suggests their association with clinical parameters of hemophilic arthropathy. Cohort studies are essential to verify these associations.

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Section: Discussionmentioning

confidence: 73%

Genetic biomarkers related to hemarthrosis, inflammation, and cartilage structure in pediatric patients with hemophilic arthropathy

López‐Jiménez

Ortega‐Cervantes²,

Luna-Záizar³

et al. 2019

Molec Gen & Gen Med

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“…Lee and colleagues 37 observed that patients with FVL mutation had lower factor concentrate consumption (mean: 310 vs. 1,185 U/kg/y) and fewer bleeding episodes. Some of these studies reported a trend in reduction of the development of hemophilic arthropathy, lower factor concentrate utilization, 38 later occurrence of the first symptomatic bleeding, 39 and attenuated bleeding manifestations 9,11,[40][41][42] in hemophilia patients carrying FVL mutation compared with those without this mutation. Protective effect of thrombophilic risk factors, including FVL, with respect to annual bleeding frequency and the severity of the hemophilic arthropathy has also been described by Kurnik and colleagues 43 and Tizzano and colleagues.…”

Section: Variability In Clinical Phenotype Of Hemophilia: Role Of Othmentioning

confidence: 99%

Defining Severity of Hemophilia: More than Factor Levels

Pavlova

Oldenburg²

2013

Semin Thromb Hemost

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Patients with severe hemophilia generally exhibit a severe bleeding phenotype with bleeding into joints or muscles at an early age. Although the severity and frequency of bleeding symptoms correlate with the residual factor VIII/IX (FVIII/IX) activity in the plasma, a considerable variability in bleeding pattern, FVIII/IX concentrate utilization, and joint damage has been observed. A subset of 10 to 15% of patients with severe hemophilia A shows a milder disease phenotype with significantly reduced frequencies of spontaneous bleeding and lower requirements for factor concentrate. This mitigated clinical phenotype is determined by the underlying mutations in the F8/F9 genes, genetic alterations and polymorphisms in other genes of the hemostasis system, differences in inflammatory and immune response genes, limitations in laboratory diagnostics, as well as environmental factors. Identification of disease-modifying factors in hemophilia may influence treatment decisions, such as starting and tailoring prophylaxis according to the specific clinical phenotype, rather than just the laboratory-defined degree of severity. This review focuses on the current information of factors mitigating the clinical presentation of hemophilia and contributing to its high phenotypic heterogeneity.

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“…2 Recently, López-Jiménez et al determined the thrombotic mutations (FVL, PT G20210A, and MTHFR) in 257 Mexican patients with hemophilia. 22 Of the 7 patients positive for investigated mutations, 5 demonstrated attenuation in hemophilia-related bleeding manifestations mostly as decreased bleeding frequency. However, in individuals heterozygous for FVL or PT G20210A, there was no additional effect of MTHFR 677TT and C677T/A1298C genotypes on bleeding phenotype.…”

Section: Discussionmentioning

confidence: 98%

Effect of Prothrombotic Mutations on Factor Consumption in Children With Hemophilia

Tüten

Çam

Özdemir

et al. 2012

Clin Appl Thromb Hemost

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Introduction: In hemophilia A, factor activity usually correlates with clinical severity; however, there are patients with severe hemophilia who have bleeding less than expected. Aim: The aim of this study is to evaluate the impact of prothrombotic mutations on annual factor consumption in children with hemophilia. Methods: Factor V Leiden (FVL) G1691A, Prothrombin (PT) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T and A128C mutations were evaluated in children with moderate–severe hemophilia A (n = 51) and controls (n = 25). Results: None of the cases and controls carried the FVL and PT G20210A in homozygous state. There was no difference in factor consumption between carriers of FVL, PT mutations, and noncarriers. Patients who were homozygous for MTHFR C677T were found to have increased factor consumption compared to noncarriers, and this was a negative association. No decrease in factor consumption was noted in patients with hemophilia having MTHFR A1298C mutation. Conclusion: We could not demonstrate a significant decrease in factor concentrate consumption in children with hemophilia having prothrombotic mutations.

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Clinical variability of haemophilia A and B in Mexican families by factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T/A1298C

Cited by 6 publications

References 10 publications

Genetic biomarkers related to hemarthrosis, inflammation, and cartilage structure in pediatric patients with hemophilic arthropathy

Genetic biomarkers related to hemarthrosis, inflammation, and cartilage structure in pediatric patients with hemophilic arthropathy

Defining Severity of Hemophilia: More than Factor Levels

Effect of Prothrombotic Mutations on Factor Consumption in Children With Hemophilia

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