Evaluation of Macrocytosis in Routine Hemograms

Original Article


Macrocytosis, a condition in which erythrocytes are larger than normal manifests as an increase in mean corpuscular volume (MCV) more than 100 fl. The aim of this study was to identify the underlying causes of macrocytosis, detected in routine hemograms and to evaluate the hematological features in different etiologies. This study included 178 adult patients whose detailed medical history was recorded, and Vitamin B12 assay, folate assay, thyroid function tests, liver function tests, complete blood counts and peripheral smear evaluation was performed. Alcoholism was identified as the etiological factor in 65 cases (36.5%), Vitamin B12 deficiency in 43 cases (24.1%) and drug related in 23 cases (12.9%). These three conditions accounted for 73.6% of macrocytosis. Other causes identified were folate deficiency, liver disease, Myelodysplastic syndrome, chronic renal failure and Aplastic anemia. In 41 cases, the cause of macrocytosis could not be explained. Anemia was observed in 95 cases (53.3%) being most common in Vitamin B12 deficiency. 9 cases (20.9%) of Vitamin B12 deficiency presented with isolated macrocytosis without anemia. It was observed that mean hemoglobin was lower and red cell distribution width (RDW) higher in megaloblastic conditions. Peripheral smear revealed hypersegmented neutrophils in 86% and macro-ovalocytes in 72% of the megaloblastic cases. Complete medical history, red cell parameters and peripheral blood smear are simple, inexpensive tools which assist in identifying the underlying cause of macrocytosis, particularly in resource limited settings. Macrocytosis needs to be evaluated even in the absence of anemia, as it may be the first clue to an underlying pathology.


Macrocytosis Megaloblastic Anemia MCV RDW 



I sincerely thank the ESI Corporation and acknowledge the encouragement and support of our Dean Dr. Rajeeva Shetty, Medical superintendent Dr. Khokhar AK, Department of Medicine and Biochemistry, Dr. Sudha Rao, Biochemist Govinda Raju V. L, laboratory technicians Prabhakar BK, Jolly Varghese, Syed Nazeer Ahmed and Venkatesh G.


  1. 1.
    Aslinia F, Mazza JJ, Yale SH (2006) Megaloblastic anemia and other causes of macrocytosis. Clin Med Res 4(3):236–241PubMedCrossRefGoogle Scholar
  2. 2.
    Hoffbrand V, Provan D (1997) ABC of clinical haematology Macrocytic anaemias. BMJ 314(8):430–433PubMedCrossRefGoogle Scholar
  3. 3.
    Kaferle J, Strzoda CE (2009) Evaluation of macrocytosis. Am Fam Physician 79(3):203–208PubMedGoogle Scholar
  4. 4.
    Thong KL, Hanley SA, Mcbride JA (1977) Clinical significance of a high mean corpuscular volume in nonanemic patients. CMA J 117:908–910Google Scholar
  5. 5.
    Seppä K, Heinilä K, Sillanaukee P, Saarni M (1996) Evaluation of macrocytosis by general practitioners. J Stud Alcohol 57:97–100PubMedGoogle Scholar
  6. 6.
    Wallerstein RO Jr (1987) Laboratory evaluation of anemia. West J Med 146:443–451PubMedGoogle Scholar
  7. 7.
    Davidson RJ, Hamilton PJ (1978) High mean red cell volume: its incidence and significance in routine haematology. J Clin Pathol 31:493–498PubMedCrossRefGoogle Scholar
  8. 8.
    Mason KD, Szer J (2005) Investigating patients with macrocytosis. Med Today 6(12):35–39Google Scholar
  9. 9.
    Bradley KA (1992) Screening and diagnosis of alcoholism in the primary care setting. West J Med 156(2):166–171PubMedGoogle Scholar
  10. 10.
    Conigrave KM, Haber P, Whitfield JB (2003) Traditional markers of excessive alcohol use. Society for the study of addiction to alcohol and other drugs, Addiction 98(Suppl 2):31–43Google Scholar
  11. 11.
    de Benoist B (2008) Conclusions of a WHO Technical Consultation on folate and Vitamin B12 deficiencies. Food Nutr Bull 29(2):S238–S244Google Scholar
  12. 12.
    Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM (1998) Wintrobe’s clinical hematology. Williams and Wilkins, BaltimoreGoogle Scholar
  13. 13.
    Snow CF (1999) Laboratory diagnosis of Vitamin B12 and folate deficiency—a guide for the primary care physician. Arch Intern Med 159:1289–1298PubMedCrossRefGoogle Scholar
  14. 14.
    Savage DG, Ogundipe A, Allen RH, Stabler SP, Lindenbaum J (2000) Etiology and diagnostic evaluation of macrocytosis. Am J Med Sci 319(6):343–352PubMedCrossRefGoogle Scholar
  15. 15.
    Keenan WF Jr (1989) Macrocytosis as an indicator of human disease. J Am Board Fam Pract 2(4):252–256PubMedGoogle Scholar
  16. 16.
    Mahmoud MY, Lugon M, Anderson CC (1996) Unexplained macrocytosis in elderly patients. Age Ageing 25:310–312PubMedCrossRefGoogle Scholar
  17. 17.
    Breedveld FC, Bieger R, van Wermeskerken RK (1981) The clinical significance of macrocytosis. Acta Med Scand 209(4):319–322PubMedGoogle Scholar
  18. 18.
    Colon-Otero G, Menke D, Hook CC (1992) A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia. Med Clin N Am 76:581–597PubMedGoogle Scholar
  19. 19.
    Sarma RP (1990) Red cell indices. In: Walker HK, Hall WD, Hurst JW (eds) Clinical methods: the history, physical, and laboratory examinations, 3rd edn. Butterworths, Boston, pp 720–723Google Scholar
  20. 20.
    Gupta PK, Saxena R, Karan AS, Choudhry VP (2003) Red cell indices for distinguishing macrocytosis of aplastic anaemia and megaloblastic anaemia. Indian J Pathol Microbiol 46(3):375–377PubMedGoogle Scholar
  21. 21.
    Khanduri U, Sharma A (2007) Megaloblastic anaemia: prevalence and causative factors. Nat Med J India 20:172–175Google Scholar
  22. 22.
    Park IK, Kim KY (1987) Clinical evaluation of red cell volume distribution width (RDW). Yonsei Med J 28(4):282–290PubMedGoogle Scholar
  23. 23.
    Seppä K, Sillanaukee P, Saarni M (1993) Blood count and hematologic morphology in nonanemic macrocytosis: differences between alcohol abuse and pernicious anemia. Alcohol 10(5):343–347PubMedCrossRefGoogle Scholar
  24. 24.
    Bessman JD, Gilmer PR Jr, Gardner FH (1983) Improved classification of anemias by MCV and RDW. Am J Clin Pathol 80(3):322–326PubMedGoogle Scholar
  25. 25.
    Lindenbaum J, Roman MJ (1980) Nutritional anemia in alcoholism. Am J Clin Nutr 33:2727–2735PubMedGoogle Scholar
  26. 26.
    Joseph AS, Cinkotai KI, Hunt L, Geary CG (1982) Natural history of smouldering leukaemia. Br J Cancer 46:160PubMedCrossRefGoogle Scholar
  27. 27.
    Carmel R (2008) Mean corpuscular volume and other concerns in the study of vitamin B-12 deficiency: epidemiology with pathophysiology. Am J Clin Nutr 87:1962–1963PubMedGoogle Scholar
  28. 28.
    Carmel R (1979) Macrocytosis, mild anemia, and delay in the diagnosis of pernicious anemia. Arch Intern Med 139:47–50PubMedCrossRefGoogle Scholar

Copyright information

© Indian Society of Haematology & Transfusion Medicine 2012

Authors and Affiliations

  1. 1.Department of PathologyESI PGIMSRBangaloreIndia
  2. 2.BangaloreIndia

Personalised recommendations