A role for homocysteine increase in haemolysis of megaloblastic anaemias due to vitamin B(12) and folate deficiency: results from an in vitro experience.

Megaloblastic anaemias (MA) are frequently associated with haemolysis. The pathogenesis of these finding is not clear, but it is thought to depend on the greater destruction of abnormal and fragile megaloblastic erythrocytes. Vitamin B(12) and folate deficiencies are the commonest cause of MA; these deficiencies may simultaneously induce a significant alteration in homocysteine metabolism leading to hyperhomocysteinemia. Blood cells have enzymes involved in homocysteine metabolism. Considering the possible effects of hyperhomocysteinemia in erythrocyte toxicity (due to oxidative damage and/or to interaction with sulfhydryl residues of structural and enzymatic proteins), the aim of our study was to evaluate (1) the homocysteine blood cells production in patients with MA due to vitamin B(12) and folate deficiency and (2) the possible role and mechanism of hyperhomocysteinemia in MA haemolysis. After incubation at 37 degrees C, blood samples from MA patients showed higher and significant levels of Hcy, LDH, lipid peroxidation parameters (MDA), and ghost protein-bound Hcy than controls. Haemolysis (%) was higher in MA patients than controls and was significantly correlated with Hcy accumulation in the medium, lipid peroxidation indices and ghost protein-bound Hcy. No significant (or significantly lower) alterations through time in considered parameters were observed in the corresponding samples incubated at 4 degrees C or in samples incubated with methionine-free medium (lower Hcy production). Our data, deriving from an in vitro experience, suggest a possible role of Hcy accumulation due to vitamin B(12) and folate deficiencies in haemolysis associated to MA due to vitamin deficiency.