Hyperhomocysteinemia as a Risk Factor for Deep-Vein Thrombosis

Heijer, Martin den; Koster, Ted; Blom, Henk J.; Bos, Gerard M.J.; Briët, E.; Reitsma, Pieter H.; Vandenbroucke, Jan P.; Rosendaal, Frits R.

doi:10.1056/nejm199603213341203

Cited by 980 publications

(501 citation statements)

References 21 publications

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“…Although in our study the mean decrease in plasma tHcy in the tamoxifen group was approximately 0.5 ,umol 1-', it was as high as 2-3 ,umol 1-' in subjects with baseline concentrations higher than 9 ,umol 1-'. Hyperhomocysteinaemia is a risk factor not only for atherothrombotic diseases but also for venous thrombosis (Falc6n et al, 1994;den Heijer et al, 1996). Thus, the sporadic risk of venous thromboembolism observed in breast cancer patients treated with tamoxifen (Fisher et al, 1989;McDonald et al, 1995) could be ascribed to the drug inhibitory effect on plasma antithrombin III (Mannucci et al, 1996) or to its partial agonistic effects on other oestrogen-regulated target systems, possibly outweighing the protective effect due to the decrease in tHcy levels.…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen reduces plasma homocysteine levels in healthy women

Cattaneo

Baglietto²,

Zighetti³

et al. 1998

Br J Cancer

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Summary Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day-' or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no cont(aindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean ± s.d. plasma levels of tHcy were 7.59 + 1.71 lmol 1-', 7.25 ± 1.61 and 7.09 + 1.33 in the tamoxifen group and 8.07 ± 2.06, 7.93 ± 1.77 and 8.12 + 2.04 in the placebo group at 0, 2 and 6 months (P= 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day-' for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Tamoxifen reduces plasma homocysteine levels in healthy women

Cattaneo

Baglietto²,

Zighetti³

et al. 1998

Br J Cancer

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“…4 Hyperhomocysteinaemia has also been linked with deep venous thrombosis, 7 vascular disease in SLE 8 and tentatively with a number of other conditions including dementia 9,10 and pre-eclampsia. 11,12 There are however problems with the current data.…”

Section: Thcy and Cardiovascular Diseasementioning

confidence: 99%

Homocysteine, hypertension and stroke

Perry

1999

J Hum Hypertens

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The balance of evidence from observational studies suggests that elevated homocysteine levels are associated with increased risk of carotid artery disease and stroke. There is however a paucity of prospective studies. There are also concerns regarding confounding due to factors associated with hyperhomocysteinemia, including renal impairment, an atherogenic diet and cigarette smoking. Homozygosity for a defective thermolabile variant of MTHFR, a common genetic polymorphism which results in hyperhomocysteinemia, has not been consistently linked with stroke or other vascular disease. There is a need for additional prospective studies with data on relevant confounders, sufficient power to characterise the form of the association between homocysteine concentrations and stroke risk, whether linear or threshold, and power to study interactions between homocysteine, other dietary markers and established stroke risk factors such as smoking and

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“…Multiple risk factors for developing a postoperative DVT have been identified and include advanced age, prolonged immobilization, obesity, and prior history (both personal and familial) of DVT or PE [19]. Moreover, a number of studies have shown hereditary prothrombotic genes and/or hematologic abnormalities lead to hypercoagulable states [3,8,12,18,19,22]. The majority of these previous studies have retrospectively observed an increased frequency of one or two abnormalities, such as activated protein C deficiency or hyperhomocysteinemia, in nonorthopaedic patients who have developed a DVT or PE.…”

Section: Introductionmentioning

confidence: 99%

Hematologic Genetic Testing in High-risk Patients Before Knee Arthroplasty: A Pilot Study

Bedair

Berli

Gezer

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Patients with a personal or familial history of thromboembolism are considered at higher risk for thromboembolic disease after knee arthroplasty. While it remains unclear why some patients develop deep vein thrombosis (DVT) or pulmonary embolism (PE) despite similar operative procedures and the same prophylactic regimen, we presume one explanation would be genetic predisposition. Questions/purposes We determined the frequency of 12 factors including antithrombin III activity, prothrombin gene mutations, and the presence of phospholipid antibodies in a high-risk patient cohort and compared those findings with the known prevalence in the population at large. Patients and Methods Patients identified preoperatively as having a personal or familial history of DVT and/or PE were referred for hemostatic serum and genetic tests, including % antithrombin III activity (ATIII), protein C and protein S activities, APC resistance, Factor V gene (Leiden) mutations, prothrombin gene mutations, lupus anticoagulant antibody presence, cardiolipin antibody presence, phosphatidyl antibody presence, b2-glycoprotein antibody presence, and serum homocysteine and lipoprotein(a) levels The frequencies of varying abnormalities were identified and compared to the prevalence reported in the literature.

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Hyperhomocysteinemia as a Risk Factor for Deep-Vein Thrombosis

Abstract: M a r t i n d e n H e u e r , M.D., T e d K o s t e r , M.D., H e n k J. B lo m , Ph.D., G e r a r d M.J. Bos, M.D., E r n e s t B r i ë t , M.D., P i e t e r H. R e its m a , P h .D ., J a n P. V a n d e n b r o ljo k e , M.D., and F rits R. R o sen d a a l, M .D .

Cited by 980 publications

References 21 publications

Tamoxifen reduces plasma homocysteine levels in healthy women

Tamoxifen reduces plasma homocysteine levels in healthy women

Homocysteine, hypertension and stroke

Hematologic Genetic Testing in High-risk Patients Before Knee Arthroplasty: A Pilot Study

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