Clinical guidelines for testing for heritable thrombophilia

Baglin, Trevor; Gray, Elaine; Greaves, M.; Hunt, Beverley J.; Keeling, David; Machin, S. J.; Mackie, Ian; Makris, Mike; Nokes, Timothy J.; Perry, David J.; Tait, R. C.; Walker, Isobel D.; Watson, Henry G.

doi:10.1111/j.1365-2141.2009.08022.x

Cited by 419 publications

(409 citation statements)

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“…62 The British Committee for Standards in Haematology and the British Society for Haematology do not include MTHFR polymorphism testing as part of their clinical guidelines for heritable thrombophilia testing. 63 The ACMG consensus statement on factor V Leiden testing briefly references the limited clinical utility of MTHFR polymorphism testing and that homocysteine measurement may be more informative. 64 A medical geneticist may be asked to evaluate a patient who has tested positive, either heterozygous or homozygous, for an MTHFR polymorphism (Box 1).…”

Section: Acmg Practice Guidelinesmentioning

confidence: 99%

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

Hickey

Curry

Toriello

2013

Genetics in Medicine

127

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Section: Acmg Practice Guidelinesmentioning

confidence: 99%

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

Hickey

Curry

Toriello

2013

Genetics in Medicine

127

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“…Considering the insufficient evidence, the professional guidelines do not recommend testing for MTHFR polymorphisms when evaluating the aetiology of VTE (College of American Pathologists, American College of Medical Genetics, The British Committee for Standards in Haematology and the British Society for Haematology); however, hyperhomocysteinemia should be measured in those found to be positive for factor V Leiden (18)(19)(20). The MTHFR C677T polymorphism is not associated with recurrences of VTE; among the carriers of genetic thrombophilic defects, only subjects presenting a positive family history of VTE are predisposed to recurrent thrombosis (21,22).…”

Section: Introductionmentioning

confidence: 99%

The Importance of Homozygous Polymorphisms of Methylenetetrahydrofolate Reductase Gene in Romanian Patients with Idiopathic Venous Thromboembolism

Popp¹,

Fodor²

2013

Balkan Med J

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IntroductionVenous thromboembolism (VTE) is a multifactorial disease, usually the result of the interaction between a genetic background predisposing to hypercoagulability and acquired risk factors. Although considered idiopathic in 25-50% of cases, investigations may detect a cause in over 80% of the patients with VTE (1). Previous studies have shown that an underlying thrombophilia could be found in about half of patients with a first episode of idiopathic VTE (1, 2). Among the "traditional" thrombophilia factors (such as protein C, protein S or antithrombin III deficiency, Factor V Leiden or Prothrombin G20210A mutations), methylenetetrahydrofolate reductase (MTHFR) polymorphisms associated with hyperhomocysteinemia have recently raised interest. The MTHFR gene encodes the enzyme MTHFR, which regulates the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the substrate for remethylation of homocysteine to methionine. The MTHFR gene is located on the short (p) arm of chromosome 1 at position 36.3. There are two common polymorphisms of the MTHFR gene: the MTHFR 677 CT polymorphism resulting in the substitution of alanine to valine at codon 222 (AlaVal) and the MTHFR 1298 AC polymorphism, resulting in a glutamine to alanine substitution (GluAla). The MTHFR C677T polymorphism, especially in the homozygous state, leads to decreased enzyme activity and hyperhomocysteinemia, whereas the MTHFR A1298C polymorphism presents a less well-defined effect, with a lesser decrease of the enzyme function.The prevalence of the T allele varies among races and ethnic groups: it is more common in Caucasians and Asians (30%) compared to African Americans (11%) (3, 4). In Europe, the lowest frequency is found in Finland (25.1%) and the Netherlands (27.4%) and the highest in Italy (45%; 47.3% in Sicily), France (34%-36%), Hungary (33.7%) and Spain (33%) (5-7). The incidence of the MTHFR C677T polymorphism in the general population is about 45% and 15% for heterozygous and homozygous genotypes, respectively. The prevalence of homozygotes for the MTHFR 677TT polymorphism in Europe varies between 5 and 15%; the heterozygous MTHFR C677T genotype presents the highest prevalence in Italy (44%) and the lowest in Norway (28%) (3,4,8,9).The role of MTHFR polymorphisms in VTE is controversial: some authors have shown an association between the MTHFR C677T polymorphism and VTE (10-14), whereas others have proven the contrary (15)(16)(17)

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“…Moreover, the real deception of this demanding clinical case was that the thrombophilia state was unknown at the time. According to the British Committee for standards in Haematology, screening the general population for thrombophilia is not recommended due to the low incidence rate of this pathological condition and cost-effectiveness concerns [10]. …”

Section: Discussionmentioning

confidence: 99%