Skip to main content

Megaloblastic and Nutritional Anemias

  • Chapter
  • First Online:
Nonmalignant Hematology
  • 1656 Accesses

Abstract

Anemia associated with a mean red cell volume (MCV) that is higher than the normal range is frequently encountered. Some patients will have multiple cytopenias while others have isolated anemia. The causes of macrocytic anemias must be distinguished in order to provide specific treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andres E, Affenberger S, Zimmer J, Vinzio S, Grosu D, Pistol G, Maloisel F, Weitten T, Kaltenbach G, Blickle JF. Current hematological findings in cobalamin deficiency. A study of 201 consecutive patients with documented cobalamin deficiency. Clin Lab Haematol. 2006;28(1):50–6.

    Article  CAS  PubMed  Google Scholar 

  • Arshi B, Shaw S. Subacute ascending numbness. Clin Toxicol (Phila). 2014;52(8):905–6.

    Article  CAS  Google Scholar 

  • Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Med Scand. 1968;184(4):247–58.

    CAS  PubMed  Google Scholar 

  • Beutler E, West C. Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood. 2005;106(2):740–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bor MV, von Castel-Roberts KM, Kauwell GP, Stabler SP, Allen RH, Maneval DR, Bailey LB, Nexo E. Daily intake of 4 to 7 microg dietary vitamin B-12 is associated with steady concentrations of vitamin B-12-related biomarkers in a healthy young population. Am J Clin Nutr. 2010;91(3):571–7.

    Article  CAS  PubMed  Google Scholar 

  • Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood. 2008;112(6):2214–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carmel R, Agrawal YP. Failures of cobalamin assays in pernicious anemia. N Engl J Med. 2012;367(4):385–6.

    Article  CAS  PubMed  Google Scholar 

  • Carmel R, Brar S, Agrawal A, Penha PD. Failure of assay to identify low cobalamin concentrations. Clin Chem. 2000;46(12):2017–8.

    CAS  PubMed  Google Scholar 

  • Castelli MC, Friedman K, Sherry J, Brazzillo K, Genoble L, Bhargava P, Riley MG. Comparing the efficacy and tolerability of a new daily oral vitamin B12 formulation and intermittent intramuscular vitamin B12 in normalizing low cobalamin levels: a randomized, open-label, parallel-group study. Clin Ther. 2011;33(3):358–371.e2.

    Article  CAS  PubMed  Google Scholar 

  • Dalsania CJ, Khemka V, Shum M, Devereux L, Lachant NA. A sheep in wolf’s clothing. Am J Med. 2008;121(2):107–9.

    Article  PubMed  Google Scholar 

  • Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev. 2008;66(5):250–5.

    Article  PubMed  Google Scholar 

  • Galloway M, Hamilton M. Macrocytosis: pitfalls in testing and summary of guidance. BMJ. 2007;335(7625):884–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore). 1991;70(4):229–45.

    Article  CAS  Google Scholar 

  • Heil SG, de Jonge R, de Rotte MC, van Wijnen M, Heiner-Fokkema RM, Kobold AC, Pekelharing JM, Adriaansen HJ, Sanders E, Trienekens PH, Rammeloo T, Lindemans J. Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study. Ann Clin Biochem. 2012;49(Pt 2):184–9.

    Article  CAS  PubMed  Google Scholar 

  • Hershko C, Ronson A, Souroujon M, Maschler I, Heyd J, Patz JV. Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood. 2006;107(4):1673–9.

    Article  CAS  PubMed  Google Scholar 

  • Honzik T, Adamovicova M, Smolka V, Magner M, Hruba E, Zeman J. Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional vitamin B12 deficiency – what have we learned? Eur J Paediatr Neurol. 2010;14(6):488–95.

    Article  PubMed  Google Scholar 

  • Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J, Rozen R. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996;93(1):7–9.

    Article  CAS  PubMed  Google Scholar 

  • Kim HI, Hyung WJ, Song KJ, Choi SH, Kim CB, Noh SH. Oral vitamin B12 replacement: an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Ann Surg Oncol. 2011a;18(13):3711–7.

    Article  PubMed  Google Scholar 

  • Kim M, Lee SE, Park J, Lim J, Cho BS, Kim YJ, Kim HJ, Lee S, Min CK, Kim Y, Cho SG. Vitamin B(12)-responsive pancytopenia mimicking myelodysplastic syndrome. Acta Haematol. 2011b;125(4):198–201.

    Article  CAS  PubMed  Google Scholar 

  • Kocaoglu C, Akin F, Caksen H, Boke SB, Arslan S, Aygun S. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother. J Health Popul Nutr. 2014;32(2):367–71.

    PubMed  PubMed Central  Google Scholar 

  • Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):1191–8.

    CAS  PubMed  Google Scholar 

  • Lewerin C, Jacobsson S, Lindstedt G, Nilsson-Ehle H. Serum biomarkers for atrophic gastritis and antibodies against Helicobacter pylori in the elderly: implications for vitamin B12, folic acid and iron status and response to oral vitamin therapy. Scand J Gastroenterol. 2008;43(9):1050–6.

    Article  CAS  PubMed  Google Scholar 

  • Limal N, Scheuermaier K, Tazi Z, Sene D, Piette JC, Cacoub P. Hyperhomocysteinaemia, thrombosis and pernicious anaemia. Thromb Haemost. 2006;96(2):233–5.

    CAS  PubMed  Google Scholar 

  • Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988;318(26):1720–8.

    Article  CAS  PubMed  Google Scholar 

  • Lindenbaum J, Savage DG, Stabler SP, Allen RH. Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol. 1990;34(2):99–107.

    Article  CAS  PubMed  Google Scholar 

  • Mechanick JI, Youdim A, Jones DB, Garvey WT, Hurley DL, McMahon MM, Heinberg LJ, Kushner R, Adams TD, Shikora S, Dixon JB, Brethauer S, American Association of Clinical Endocrinologists; Obesity Society; American Society for Metabolic & Bariatric Surgery. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient-2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society and American Society for Metabolic & Bariatric Surgery. Obesity (Silver Spring). 2013;21 Suppl 1:S1–27.

    Article  CAS  Google Scholar 

  • Mushtak A, Yousef Khan F, Aldehwe B, Abdulrahman Al-Ani A. Three different presentation of same pathophysiology. Acta Inform Med. 2012;20(3):190–1.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nachum-Biala Y, Troen AM. B-vitamins for neuroprotection: narrowing the evidence gap. Biofactors. 2012;38(2):145–50.

    Article  CAS  PubMed  Google Scholar 

  • Nexo E, Hoffmann-Lucke E. Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility. Am J Clin Nutr. 2011;94(1):359S–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nielsen MJ, Rasmussen MR, Andersen CB, Nexo E, Moestrup SK. Vitamin B12 transport from food to the body’s cells – a sophisticated, multistep pathway. Nat Rev Gastroenterol Hepatol. 2012;9(6):345–54.

    Article  CAS  PubMed  Google Scholar 

  • Parmentier S, Meinel J, Oelschlaegel U, Mohr B, Ehninger G, Schaich M, Platzbecker U. Severe pernicious anemia with distinct cytogenetic and flow cytometric aberrations mimicking myelodysplastic syndrome. Ann Hematol. 2012;91(12):1979–81.

    Article  PubMed  Google Scholar 

  • Pennypacker LC, Allen RH, Kelly JP, Matthews LM, Grigsby J, Kaye K, Lindenbaum J, Stabler SP. High prevalence of cobalamin deficiency in elderly outpatients. J Am Geriatr Soc. 1992;40(12):1197–204.

    Article  CAS  PubMed  Google Scholar 

  • Pittock SJ, Payne TA, Harper CM. Reversible myelopathy in a 34-year-old man with vitamin B12 deficiency. Mayo Clin Proc. 2002;77(3):291–4.

    Article  PubMed  Google Scholar 

  • Remacha AF, Souto JC, Pinana JL, Sardà MP, Queralto JM, Marti-Fabregas J, Garcia-Moll X, Fernandez C, Rodriguez A, Cuesta J. Vitamin B12 deficiency, hyperhomocysteinemia and thrombosis: a case and control study. Int J Hematol. 2011;93(4):458–64.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Schrempf W, Eulitz M, Neumeister V, Siegert G, Koch R, Reichmann H, Storch A. Utility of measuring vitamin B12 and its active fraction, holotranscobalamin, in neurological vitamin B12 deficiency syndromes. J Neurol. 2011;258(3):393–401.

    Article  CAS  PubMed  Google Scholar 

  • Sekhar J, Stabler SP. Life-threatening megaloblastic pancytopenia with normal mean cell volume: case series. Eur J Intern Med. 2007;18(7):548–50.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shah DR, Daver N, Borthakur G, Hirsch-Ginsberg C, Oo TH. Pernicious anemia with spuriously normal vitamin B12 level might be misdiagnosed as myelodysplastic syndrome. Clin Lymphoma Myeloma Leuk. 2014;14(4):e141–3.

    Article  PubMed  Google Scholar 

  • Stabler SP. Megaloblastic anemias: pernicious anemia and folate deficiency. In: Young NS, Green SL, High KA, editors. Clinical hematology. Philadelphia: Mosby Elsevier; 2006. p. 242–51.

    Google Scholar 

  • Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149–60.

    Article  CAS  PubMed  Google Scholar 

  • Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr. 2004;24:299–326.

    Article  CAS  PubMed  Google Scholar 

  • Stabler SP, Korson M, Jethva R, Allen RH, Kraus JP, Spector EB, Wagner C, Mudd SH. Metabolic profiling of total homocysteine and related compounds in hyperhomocysteinemia: utility and limitations in diagnosing the cause of puzzling thrombophilia in a family. JIMD Rep. 2013;11:149–63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tadakamalla AK, Talluri SK, Besur S. Pseudo-thrombotic thrombocytopenic purpura: a rare presentation of pernicious anemia. N Am J Med Sci. 2011;3(10):472–4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Toh BH, Chan J, Kyaw T, Alderuccio F. Cutting edge issues in autoimmune gastritis. Clin Rev Allergy Immunol. 2012;42(3):269–78.

    Article  CAS  PubMed  Google Scholar 

  • Vuckovic BA, van Rein N, Cannegieter SC, Rosendaal FR, Lijfering WM. Vitamin supplementation on the risk of venous thrombosis: results from the MEGA case-control study. Am J Clin Nutr. 2015;101(3):606–12.

    Article  CAS  PubMed  Google Scholar 

  • Whyte AF, Jones DL, Dreyer MD. Vitamin B12 deficiency causing hyperhomocysteinaemia and cerebral venous sinus thrombosis. Intern Med J. 2012;42(5):601–3.

    Article  CAS  PubMed  Google Scholar 

  • Wickramasinghe SN. Diagnosis of megaloblastic anaemias. Blood Rev. 2006;20(6):299–318.

    Article  CAS  PubMed  Google Scholar 

  • Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, Stoll C, Alembik Y, Dott B, Czeizel AE, Gelman-Kohan Z, Scarano G, Bianca S, Ettore G, Tenconi R, Bellato S, Scala I, Mutchinick OM, López MA, de Walle H, Hofstra R, Joutchenko L, Kavteladze L, Bermejo E, Martínez-Frías ML, Gallagher M, Erickson JD, Vollset SE, Mastroiacovo P, Andria G, Botto LD. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide. J Med Genet. 2003;40(8):619–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wollman MR, Penchansky L, Shekhter-Levin S. Transient 7q- in association with megaloblastic anemia due to dietary folate and vitamin B12 deficiency. J Pediatr Hematol Oncol. 1996;18(2):162–5.

    Article  CAS  PubMed  Google Scholar 

  • Wun Chan JC, Yu Liu HS, Sang Kho BC, Yin Sim JP, Hang Lau TK, Luk YW, Chu RW, Fung Cheung FM, Tat Choi FP, Kwan Ma ES. Pernicious anemia in Chinese: a study of 181 patients in a Hong Kong hospital. Medicine (Baltimore). 2006;85(3):129–38.

    Article  Google Scholar 

  • Yang DT, Cook RJ. Spurious elevations of vitamin B12 with pernicious anemia. N Engl J Med. 2012;366(18):1742–3.

    Article  CAS  PubMed  Google Scholar 

  • Yang HT, Lee M, Hong KS, Ovbiagele B, Saver JL. Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials. Eur J Intern Med. 2012;23(8):745–54.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sally P. Stabler MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Stabler, S.P. (2016). Megaloblastic and Nutritional Anemias. In: Abutalib, S., Connors, J., Ragni, M. (eds) Nonmalignant Hematology. Springer, Cham. https://doi.org/10.1007/978-3-319-30352-9_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-30352-9_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-30350-5

  • Online ISBN: 978-3-319-30352-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics