Megaloblastic anaemia: Prevalence and causative factors

Background: Megaloblastic anaemia is not uncommon in India, but data are insufficient regarding its prevalence, and causative and precipitating factors. We did a prospective study to document such data for patients of megaloblastic anaemia.

Methods: All patients presenting to our hospital over a period of 6 months with a haemoglobin <10 g/dl and/or mean corpuscular volume >95 fL and blood film findings consistent with megaloblastosis were included in the study. Demographic data, diet, drug intake, previous blood transfusion and presenting symptoms were recorded. Clinical findings were obtained from medical records of patients. Complete blood counts, blood film examination, reticulocyte count and cobalamin and folate assays were done. Results of liver function tests and bone marrow slides were available for review.

Results: Megaloblastic anaemiawas diagnosed in 175 patients with anaemia. Assays were done on 120 patients (55 were lost to follow up) and results showed cobalamin deficiency in 78 patients (65%), combined cobalamin and folate deficiency in 20 patients (12%) and pure folate deficiency in 8 patients (6%). Fifteen per cent of patients had normal or high values of both vitamins, having received blood or haematinics before the diagnosis was established. The peak incidence of megaloblastic anaemia was in the age group of 10–30 years (48%), with female preponderance (71%). The predominant symptoms were fatigue, anorexia and gastritis, low grade fever, shortness of breath, palpitations and mild jaundice. Twenty-five per cent of patients were on acid-suppressing medication and 15% had previous transfusion for anaemia. Eighty-seven per cent of patients with cobalamin deficiency and 75% with folate deficiency were lactovegetarians. In the combined deficiency cohort, 71% were vegetarians and 29% were occasional non-vegetarians. Physical findings were pallor (85%), glossitis (29%), mild icterus (25%) and hyperpigmentation (18%). Abnormal haematological findings were mean corpuscular volume 77–123 fL (9 patients had iron deficiency), red cell distribution width 16%–44%, pancytopenia in 62% of patients, reticulocyte count >2% in 42% of patients and typical megaloblastic blood films in all patients. Bone marrow smears available in 22 patients showed moderate-to-severe megaloblastosis. Thirty-two per cent of patients in whom liver function tests were done showed indirect bilirubinaemia with normal enzymes.

Conclusion: Megaloblastic anaemia was diagnosed from complete blood counts, red cell indices, blood film examination and assays of the two vitamins. Bone marrow examination was not essential for diagnosis. Cobalamin deficiency was the major cause of megaloblastosis. Aetiological factors were a diet poor in cobalamin or folate, increased requirements during the growth period and pregnancy, and the use of acid-suppressing medication. Physicians managing these patients need to be aware of the timing of blood sampling for assays, that haematinics and transfusions provide only short term benefits, and that long term follow up and diet counselling is crucial.