Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Macrocytosis/Macrocytic anemia

Stanley L Schrier, MD
Section Editor
William C Mentzer, MD
Deputy Editor
Jennifer S Tirnauer, MD


Macrocytosis is a descriptive term for red blood cell (RBC) size larger than the normal range. It may be caused by abnormalities of RBC production in the bone marrow, altered RBC membrane composition, or an increase in the percentage of reticulocytes, which are larger than mature RBCs. This topic discusses causes of macrocytosis and macrocytic anemia. Additional topics discuss the following:

Microcytosis/microcytic anemia – (See "Microcytosis/Microcytic anemia".)

General anemia evaluation

Child – (See "Approach to the child with anemia".)

Adult – (See "Approach to the adult patient with anemia".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Oct 03, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Hoffbrand V, Provan D. ABC of clinical haematology. Macrocytic anaemias. BMJ 1997; 314:430.
  2. 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; 76:581.
  3. d'Onofrio G, Chirillo R, Zini G, et al. Simultaneous measurement of reticulocyte and red blood cell indices in healthy subjects and patients with microcytic and macrocytic anemia. Blood 1995; 85:818.
  4. Houwen B. Reticulocyte maturation. Blood Cells 1992; 18:167.
  5. Shuster S, Marks J, Chanarin I. Folic acid deficiency in patients with skin disease. Br J Dermatol 1967; 79:398.
  6. Borgna-Pignatti C, Azzalli M, Pedretti S. Thiamine-responsive megaloblastic anemia syndrome: long term follow-up. J Pediatr 2009; 155:295.
  7. Viana MB, Carvalho RI. Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: A new syndrome? J Pediatr 1978; 93:235.
  8. Porter FS, Rogers LE, Sidbury JB Jr. Thiamine-responsive megaloblastic anemia. J Pediatr 1969; 74:494.
  9. Aycan Z, Baş VN, Cetinkaya S, et al. Thiamine-responsive megaloblastic anemia syndrome with atrial standstill: a case report. J Pediatr Hematol Oncol 2011; 33:144.
  10. Srikrupa NN, Meenakshi S, Arokiasamy T, et al. Leber's congenital amaurosis as the retinal degenerative phenotype in thiamine responsive megaloblastic anemia: a case report. Ophthalmic Genet 2014; 35:119.
  11. Hesdorffer CS, Longo DL. Drug-Induced Megaloblastic Anemia. N Engl J Med 2015; 373:1649.
  12. Karvellas CJ, Sawyer M, Hamilton M, Mackey JR. Effect of capecitabine on mean corpuscular volume in patients with metastatic breast cancer. Am J Clin Oncol 2004; 27:364.
  13. Snower DP, Weil SC. Changing etiology of macrocytosis. Zidovudine as a frequent causative factor. Am J Clin Pathol 1993; 99:57.
  14. Burns ER, Reed LJ, Wenz B. Volumetric erythrocyte macrocytosis induced by hydroxyurea. Am J Clin Pathol 1986; 85:337.
  15. Engström KG, Löfvenberg E. Treatment of myeloproliferative disorders with hydroxyurea: effects on red blood cell geometry and deformability. Blood 1998; 91:3986.
  16. Gillessen S, Graf L, Korte W, Cerny T. Macrocytosis and cobalamin deficiency in patients treated with sunitinib. N Engl J Med 2007; 356:2330.
  17. Billemont B, Izzedine H, Rixe O. Macrocytosis due to treatment with sunitinib. N Engl J Med 2007; 357:1351.
  18. Rini BI, Choueiri TK, Elson P, et al. Sunitinib-induced macrocytosis in patients with metastatic renal cell carcinoma. Cancer 2008; 113:1309.
  19. Schallier D, Trullemans F, Fontaine C, et al. Tyrosine kinase inhibitor-induced macrocytosis. Anticancer Res 2009; 29:5225.
  20. Rajaraman S, Davis WS, Mahakali-Zama A, et al. An allelic series of mutations in the Kit ligand gene of mice. II. Effects of ethylnitrosourea-induced Kitl point mutations on survival and peripheral blood cells of Kitl(Steel) mice. Genetics 2002; 162:341.
  21. Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis. Clin Med Res 2006; 4:236.
  22. Kaferle J, Strzoda CE. Evaluation of macrocytosis. Am Fam Physician 2009; 79:203.
  23. Seppä K, Sillanaukee P, Saarni M. Blood count and hematologic morphology in nonanemic macrocytosis: differences between alcohol abuse and pernicious anemia. Alcohol 1993; 10:343.
  24. Savage D, Lindenbaum J. Anemia in alcoholics. Medicine (Baltimore) 1986; 65:322.
  25. Girard DE, Kumar KL, McAfee JH. Hematologic effects of acute and chronic alcohol abuse. Hematol Oncol Clin North Am 1987; 1:321.
  26. Balcells A, Ingelmo M, Vivancos J, et al. [Macrocytosis in chronic alcoholism (author's transl)]. Med Clin (Barc) 1979; 73:312.
  27. Wymer A, Becker DM. Recognition and evaluation of red blood cell macrocytosis in the primary care setting. J Gen Intern Med 1990; 5:192.
  28. Seppä K, Laippala P, Saarni M. Macrocytosis as a consequence of alcohol abuse among patients in general practice. Alcohol Clin Exp Res 1991; 15:871.
  29. Latvala J, Parkkila S, Melkko J, Niemelä O. Acetaldehyde adducts in blood and bone marrow of patients with ethanol-induced erythrocyte abnormalities. Mol Med 2001; 7:401.
  30. Wickramasinghe SN, Malik F. Acetaldehyde causes a prolongation of the doubling time and an increase in the modal volume of cells in culture. Alcohol Clin Exp Res 1986; 10:350.
  31. Hashimoto Y, Nakayama T, Futamura A, et al. Erythrocyte mean cell volume and genetic polymorphism of aldehyde dehydrogenase 2 in alcohol drinkers. Blood 2002; 99:3487.
  32. Carvalho NF, Kenney RD, Carrington PH, Hall DE. Severe nutritional deficiencies in toddlers resulting from health food milk alternatives. Pediatrics 2001; 107:E46.
  33. Horton L, Coburn RJ, England JM, Himsworth RL. The haematology of hypothyroidism. Q J Med 1976; 45:101.
  34. Hinchliffe RF, Bellamy GJ, Lilleyman JS. Use of the Technicon H1 hypochromia flag in detecting spurious macrocytosis induced by excessive K2-EDTA concentration. Clin Lab Haematol 1992; 14:268.
  35. Holt JT, DeWandler MJ, Arvan DA. Spurious elevation of the electronically determined mean corpuscular volume and hematocrit caused by hyperglycemia. Am J Clin Pathol 1982; 77:561.
  36. van Duijnhoven HL, Treskes M. Marked interference of hyperglycemia in measurements of mean (red) cell volume by Technicon H analyzers. Clin Chem 1996; 42:76.
  37. Weiss GB, Bessman JD. Spurious automated red cell values in warm autoimmune hemolytic anemia. Am J Hematol 1984; 17:433.
  38. Bessman JD, Banks D. Spurious macrocytosis, a common clue to erythrocyte cold agglutinins. Am J Clin Pathol 1980; 74:797.
  39. Goossens W, Van Duppen V, Verwilghen RL. K2- or K3-EDTA: the anticoagulant of choice in routine haematology? Clin Lab Haematol 1991; 13:291.
  40. Rauw J, Wells RA, Chesney A, et al. Validation of a scoring system to establish the probability of myelodysplastic syndrome in patients with unexplained cytopenias or macrocytosis. Leuk Res 2011; 35:1335.
  41. Inelmen EM, D'Alessio M, Gatto MR, et al. Descriptive analysis of the prevalence of anemia in a randomly selected sample of elderly people living at home: some results of an Italian multicentric study. Aging (Milano) 1994; 6:81.
  42. den Elzen WP, Westendorp RG, Frölich M, et al. Vitamin B12 and folate and the risk of anemia in old age: the Leiden 85-Plus Study. Arch Intern Med 2008; 168:2238.
  43. Lam AP, Gundabolu K, Sridharan A, et al. Multiplicative interaction between mean corpuscular volume and red cell distribution width in predicting mortality of elderly patients with and without anemia. Am J Hematol 2013; 88:E245.
  44. Christensen RD, Jopling J, Henry E, Wiedmeier SE. The erythrocyte indices of neonates, defined using data from over 12,000 patients in a multihospital health care system. J Perinatol 2008; 28:24.
  45. Dallman PR, Siimes MA. Percentile curves for hemoglobin and red cell volume in infancy and childhood. J Pediatr 1979; 94:26.
  46. Pappo AS, Fields BW, Buchanan GR. Etiology of red blood cell macrocytosis during childhood: impact of new diseases and therapies. Pediatrics 1992; 89:1063.
  47. Davenport J. Macrocytic anemia. Am Fam Physician 1996; 53:155.
  48. Anttila P, Ihalainen J, Salo A, et al. Idiopathic macrocytic anaemia in the aged: molecular and cytogenetic findings. Br J Haematol 1995; 90:797.
  49. Planche V, Georgin-Lavialle S, Avillach P, et al. Etiologies and diagnostic work-up of extreme macrocytosis defined by an erythrocyte mean corpuscular volume over 130°fL: A study of 109 patients. Am J Hematol 2014; 89:665.