Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: a case series

Abstract

BackgroundHyperhomocysteinemia has been suspected of favoring thrombosis. Several case–control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is due to genetic and acquired factors (poor diet in folate and vitamin B12, older age, renal impairment, thyroid diseases, and malignancies) induced by the intake and the concentrations of vitamin B9 or B12 in the majority of cases.Cases presentationWe report the cases of four Moroccan patients who presented with acute vein thrombosis of different sites: a 34-year-old man, a 60-year-old man, a 58-year-old man, and a 47-year-old woman. All patients had a low level of cobalamin with marked hyperhomocysteinemia with normal serum and red cell folic acid. Venous thrombosis revealed pernicious anemia in all patients. Their low levels of cobalamin, atrophic gastritis, and positive results for gastric parietal cell antibodies confirmed the diagnosis of pernicious anemia. There was no evidence of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, or hormone replacement therapy. No deficiencies in protein C and protein S were detected; they had normal antithrombin III function and factor V Leiden; no prothrombin gene mutations were detected. Treatment included orally administered anticoagulation therapy and cobalamin supplementation. The outcome was favorable in all cases.ConclusionsThese reports demonstrate that pernicious anemia, on its own, can lead to hyperhomocysteinemia that is significant enough to lead to thrombosis. Understanding the molecular pathogenesis of the development of thrombosis in patients with hyperhomocysteinemia related to Biermer disease would help us to identify patients at risk and to treat them accordingly. The literature concerning the relationship between homocysteine and venous thrombosis is briefly reviewed.

Intrauterine Growth Retardation Complicated by Biermer’s Disease: An Observation in Togo

“…Biermer's disease (formerly called pernicious anemia) is an autoimmune atrophic gastritis, predominantly fundic, responsible for vitamin B12 deficiency (cobalamin) by malabsorption of the latter [1]. Vitamin B12 is the cofactor of methylmalonyl mutase and methionine synthetase.…”

“…This modification induces the aggregation of proteins, a phenomenon involved in many neurodegenerative diseases. The combination of these different mechanisms sheds new light on the developmental defects and cognitive disorders associated with early methyl donor deficiency, highlighting the importance of “fetal programming” in the occurrence of certain neurological pathologies [1, 12]. The patient had an increase in homocysteine that allows us to understand the IUGR and then the hypotonia at birth and the secondary stunted weight loss.…”

“…Biermer's disease (BD) also called pernicious anemia is an autoimmune atrophic gastritis with dryness of Castle's intrinsic factor (IF) responsible for vitamin B12 deficiency. It is usually diagnosed in the presence of megaloblastic anemia, neurologic symptoms, or atrophic gastritis [1]. This entity accounts for more than 25% of the etiologies of vitamin B12 deficiency in adults and results from malabsorption caused by autoimmune gastritis [2].…”

“…It is manifested by anemic and/or digestive and/or neurological signs. The diagnosis is based on the demonstration of chronic atrophic gastritis, the positivity of anti-FI (anti-intrinsic factor) and/or anti-GPC (antigastric parietal cell) autoantibodies in the serum, and/or the decrease of selective vitamin B12 [1]. The association of Biermer's disease with autoimmune diseases such as type 1 diabetes (insulin-dependent), autoimmune thyroiditis (especially Hashimoto's), or vitiligo is common [3].…”

“…The association of Biermer's disease with autoimmune diseases such as type 1 diabetes (insulin-dependent), autoimmune thyroiditis (especially Hashimoto's), or vitiligo is common [3]. Through an increase of homocysteine induced by vitamin B12 deficiency, several studies have reported venous thrombosis during Biermer's disease [1, 4]. During pregnancy, the causes or factors associated with an increased risk of intrauterine growth retardation (IUGR) are extremely numerous and can be grouped into maternal, placental, and fetal anemia [5].…”