Evaluation of clinical, biochemical and hematological parameters in macrocytic anemia

Aarthi Kannan, Vijai Tilak, Madhukar Rai, Vineetha Gupta


Background: Macrocytosis is a common finding encountered in automated coulters and evaluation of clinical, biochemical and haematological parameters in macrocytic anemias will provide a clue to diagnosis. This study was done to evaluate the clinical and laboratory parameters in macrocytic anemias and their utility in differentiating megaloblastic and non-megaloblastic anemia.

Methods: 100 patients presenting with macrocytosis were taken in to study. A detailed clinical history and physical examination was done in all cases. CBC, biochemical investigations, peripheral blood examination and reticulocyte count was done in all cases and Vitamin B12 and folate levels, bone marrow aspiration and bone marrow biopsy in some cases. After evaluation, a provisional diagnosis was made and patients with megaloblastic anaemia was given vitamin B12 and folic acid treatment and followed up after 2 weeks and 1 month.

Results: Primary bone marrow disorders were the most common cause of macrocytosis (46%). The other causes in decreasing order of frequency were megaloblastic anaemia (38%), hemolytic anemia (6%), drug induced (5%), alcoholism and liver disease (4%) and idiopathic thrombocytopenic purpura (1%). There was a significant difference in the mean values of MCV and serum LDH between megaloblastic and non – megaloblastic macrocytosis. When serum LDH >1345.2 IU/L or MCV>121fl (criterion values of ROC curve) with reticulocyte count <2% was taken as criteria, the sensitivity was 92.1% and specificity was 93.5% for diagnosing megaloblastic anemia.

Conclusions: Systematic evaluation of macrocytosis will help us to distinguish megaloblastic and non – megaloblastic macrocytosis. The blood and biochemical parameters especially CBC, RC, and serum LDH along with supporting clinical features help us in diagnosing megaloblastic anemia in a setup where vitamin and metabolite levels are difficult to obtain.



Megaloblastic anemia, Macrocytosis, Non-megaloblastic macrocytosis, Serum LDH, Mean corpuscular volume, Anemia

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Davidson RJL, Hamilton PJ. High mean red cell volume: its incidence and significance in routine haematology. J Clin Pathol. 1978;31(5):493-8.

Breedveld FC, Bieger R, van Wermeskerken RK. The clinical significance of macrocytosis. Acta Med Scand. 1981;209(4): 319-22.

Colon-Otero G, Menke D, Hook CC. A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia. Med Clin North Am. 1992;76(3):581-97

Wymer A, Becker DM: Recognition and evaluation of red cell macrocytosis in the primary care setting. J Gen Intern Med. 1990;5(3):192-7.

Savage DG, Ogundipe A, Allen RH, Stabler SP, Lindenbaum J. Etiology and diagnostic evaluation of macrocytosis. Am J Med Sci. 2000;319(6):343-52.

Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med. 1994;96(3):239-46.

Savage DG, Allen RH, Gangaidzo IT, Levy LM, Gwanzura C, Moyo A, et al. Pancytopenia in Zimbabwe. Am J Med Sci. 1999;317(1):22-32.

Savage DG, Gangaidzo IT, Lindenbaum J, Kiire C, Mukiibi JM, Moyo A, et al. Vitamin B12 deficiency is the primary cause of megaloblastic anemia in Zimbabwe. Br J Haematol. 1994;86(4):844-50.

McPhedran, P, Barnes MG, Weinstein JS, Robertson JS. Interpretation of electronically determined macrocytosis. Annals of Internal Medicine. 1973;78(5):677-83.

Unnikrishnan V, Dutta TK, Badhe BA, Bobby Z, Panigrahi AK. Clinico – aetiologic profile of macrocytic anemias with special reference to megaloblastic anemia. Indian J. Hematol. Blood Transfus. 2008;24(4):155-65.

Bridgen ML. A systemic approach to macrocytosis. sorting out the cases. Postgrad Med. 1995;97(5):171-2, 175-7, 181-4 passim.

Lee GR. Anemia: a diagnostic strategy. In: Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM, Wintrobe MM editors. Wintrobe’s clinical hematology, 10th ed. Baltimore: Williams & Wilkins. 1998;908-40.

Mahmoud MY, Lugon M, Anderson CC. Unexplained Macrocytosis in Elderly Patients. Age and ageing. 1996;25(4):310-2.

Khanduri U and Sharma A. Megaloblastic anaemia: prevalence and causative factors. The national medical journal of india. 2007;20(4):172-5.

Marshall RA. A review of lesions in the optic fundus in various diseases of the blood. Blood. 1959;14(7):882-91.

Aisen ML, Bacon BR, Goodman AM, et al. Retinal abnormalities associated with anemia. Arch Ophthalmol. 1983;101(7): 1049-52.

Merin S, Freund M. Retinopathy in severe anemia. Am J Ophthalmol. 1968;66(6):1102-6.

Goldfarb TG, Papp BJ. Excessively high levels of lactic acid dehydrogenase activity in pernicious anemia. Am J Med. 1963;34:578-622.

Gordin R, Eanri TM. Lactic dehydrogenase in vitamin B12 deficiency. Acta Hematol. 1959;21(1):16-22.

Emerson PM, Wilkinson JH. Lactate dehydrogenase in the diagnosis and assessment of response to treatment of megaloblastic anemia. Brit J Hematol. 1966;12(6):678-87.

Jaswal TS, Mehta HC, Gupta V, Singh M, Singh S. Serum Lactate Dehydrogenase in diagnosis of megaloblastic anemia. Indian J. Pathol. Microbiol. 2000;43(3): 325-9.

Emerson PM, Withycome WA, Wilkinson JH. The origin of the elevated serum lactate dehydrogenase in megaloblastic anemia. Brit. J. Hematol. 1967;13(5):656-64.

Aitelli, Cristi BS, Wasson, Lori DO, Ray Page, DO. Pernicious Anemia: Presentations Mimicking Acute Leukemia. Southern Medical Journal. 2004;97(3):295-7.