Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study

Quéré, Isabelle; Perneger, Thomas; Zittoun, J; Bellet, H.; Gris, Jean‐Christophe; Daurès, Jean‐Pierre; Schved, Jean‐François; Mercier, É.; Laroche, J.-P.; Dauzat, M.; Bounameaux, Henri; Janbon, C; Moerloose, Philippe de

doi:10.1016/s0140-6736(02)07876-5

Cited by 84 publications

(30 citation statements)

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“…45 The current findings concerning homocysteine evidence a significant risk associated with traditionally normal homocysteine plasma concentrations, recalling what we have previously described for venous thromboembolism. 17 The question of whether homocysteine concentrations are causally related to early miscarriage remains debatable. Published data only support hyperhomocysteinemia as a risk factor for recurrent early pregnancy loss, 20 but the pathophysiology of this relationship is basically not elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…16 One may speculate that antibodies against these glycoproteins can modulate the placental thrombotic risk. Moderate hyperhomocysteinemia, a risk factor for thromboembolism, 17 seems to influence the thrombotic tendency in patients with primary 18 or secondary 19 antiphospholipid syndrome and is involved in pregnancy failure. 20 The objective of the present study was to determine whether women with a first episode of spontaneous pregnancy loss during the eighth and ninth weeks of gestation were more likely to have moderate levels of some hemostasis-related autoantibodies: traditional antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies), nontraditional antiphospholipid antibodies (antiphosphatidylethanolamine, anti-␤2-glycoprotein I, and antiannexin V antibodies), antihemostasis-related key glycoproteins antibodies (antitissue factor, antithrombomodulin, anti-t-PA), or a moderate hyperhomocysteinemia.…”

Section: Introductionmentioning

confidence: 99%

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Antiphospholipid/antiprotein antibodies, hemostasis-related autoantibodies, and plasma homocysteine as risk factors for a first early pregnancy loss: a matched case-control study

Gris

Perneger

Quéré

et al. 2003

Blood

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antiphospholipid/antiprotein antibodies, hemostasis-related autoantibodies, and plasma homocysteine as risk factors for a first early pregnancy loss: a matched case-control study

Gris

Perneger

Quéré

et al. 2003

Blood

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“…As folates may be involved in thrombotic risk, 16 all patients were taking therapeutic doses of folic acid, 5 mg daily, at least 1 month before conception. This treatment was continued during all new ongoing pregnancies.…”

Section: Treatment Regimensmentioning

confidence: 99%

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

Gris

Mercier

Quéré

et al. 2004

Blood

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The prospective evaluation of the effect of thromboprophylaxis in women with one unexplained pregnancy loss from the 10th week of amenorrhea was performed. A total of 160 patients with heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency were given 5 mg folic acid daily before conception, to be continued during pregnancy, and low-dose aspirin 100 mg daily or low-molecular-weight heparin enoxaparin 40 mg was taken from the 8th week. Twenty-three of the 80 patients

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“…In the elder child, the use of oral contraceptives was probably an aggravating factor in the occurrence of pulmonary embolism which revealed her congenital disease that had remained silent until adulthood. In addition, low methylfolate levels must be considered because they have been found to be associated with a higher risk of venous thrombosis (Quéré et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

Severe methylenetetrahydrofolate reductase deficiency revealed by a pulmonary embolism in a young adult

Tonetti¹,

Ruivard

Rieu

et al. 2002

Br J Haematol

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Summary. Deficiency in methylenetetrahydrofolate reductase (MTHFR), the enzyme involved in the remethylation of homocysteine to methionine using methyltetrahydrofolate as cofactor, induces hyperhomocysteinaemia, homocysteinuria, hypomethioninaemia and low methylfolate levels. Diagnosis usually occurs during infancy because of various neurological abnormalities. We report MTHFR deficiency diagnosed in an adult woman after a pulmonary embolism. Her adult sister, intellectually retarded, suffered from the same disease. Molecular analysis of the MTHFR gene exhibited four different mutations (two missense mutations, one exon skipping and C677T). The impact of these mutations was analysed through the biological abnormalities in the parents and children.Keywords: hyperhomocysteinaemia, pulmonary embolism, MTHFR deficiency, molecular analysis, methylfolate.Among the risk factors of thrombophilia, hyperhomocysteinaemia is responsible for venous and arterial thrombotic diseases (Welch & Loscalzo, 1998).Elevation of plasma homocysteine results from inherited or nutritional factors. Severe hyperhomocysteinaemia is due to enzyme deficiencies. Cystathionine b-synthase, present on the trans-sulphuration pathway, changes homocysteine to cystathionine, by using vitamin B 6 as coenzyme, and is associated with precocious vascular disease. Methylenetetrahydrofolate reductase (MTHFR) catalyses the synthesis of 5-methyltetrahydrofolate, the methyl donor for the vitamin B 12 -dependent remethylation of homocysteine to methionine via methionine synthase (Rosenblatt, 2001). Among various mutations on the MTHFR gene, a thermolabile variant caused by a point mutation in exon 4 of the gene (C677fiT) (AlafiVal) usually induces mild hyperhomocysteinaemia, moderate decreased MTHFR activity and decreased folate status . Nutritional deficiency in the vitamin cofactors (folate, vitamin B 12 and vitamin B 6 ) required for homocysteine metabolism may promote hyperhomocysteinaemia.We report a case of severe pulmonary embolism in a young adult taking oral contraceptives without any known factor of thrombophilia, in whom hyperhomocysteinaemia and hypomethioninaemia related to severe MTHFR deficiency were found. Genetic studies of the family identified three mutations on the MTHFR gene, two of them novel and the C677fiT mutation. The impact of these mutations is discussed. CASE REPORTThe patient, an obese 27-year-old woman, developed dyspnoea 8 months after taking oral contraceptives. One year before, she delivered a healthy child after a normal pregnancy. Since her childhood, she had walking problems, and she encountered difficulties at school. Neurological examination revealed bilateral Babinski signs. Helical computerized tomography showed bilateral pulmonary embolism and duplex ultrasonography revealed left iliac vein thrombosis. When factors associated with thrombophilia (blood levels of antithrombin, protein C, protein S, antiphospholipid antibodies, lupus anticoagulant, analysis of factor V Leiden and prothrombin G20210) were screened, no abnor...

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Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study

Cited by 84 publications

References 28 publications

Antiphospholipid/antiprotein antibodies, hemostasis-related autoantibodies, and plasma homocysteine as risk factors for a first early pregnancy loss: a matched case-control study

Antiphospholipid/antiprotein antibodies, hemostasis-related autoantibodies, and plasma homocysteine as risk factors for a first early pregnancy loss: a matched case-control study

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

Severe methylenetetrahydrofolate reductase deficiency revealed by a pulmonary embolism in a young adult

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