Macrocytosis Clinical Presentation

  • Author: Joseph E Maakaron, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Feb 10, 2012
 

History

The symptoms of macrocytosis are attributable either to the anemia itself or to the underlying condition causing the anemia. They may include the following:

  • Dyspnea – This is a consequence of anemia; in acute or severe anemia, the volume of hemoglobin in the blood is inadequate to provide appropriate oxygenation of the tissues
  • Headache – This is a symptom of anemia due to decreased oxygenation of the tissues
  • Fatigue – This may be attributed to underlying disease, if present, or to inadequate blood volume
  • Sore tongue – This may reflect glossitis or atrophy of the tongue, which are common findings in folate and vitamin B-12 deficiencies[10]
  • Diarrhea or other gastrointestinal (GI) symptoms – These may be present in patients with tropical or celiac sprue; sprue may cause folate or vitamin B-12 deficiencies[11]
  • Paresthesia or gait disturbances – These suggest vitamin B-12 deficiency

A history of alcohol abuse may be an important clue to the cause of the increased mean cell volume (MCV); long-term use of alcohol may have a direct toxic effect on the bone marrow, causing macrocytosis.[12] A thorough examination of the patient’s medication regimen is also crucial in the workup of macrocytosis; a variety of medications may have an effect on the MCV. Recent acute blood loss may signal that reticulocytosis is causing the MCV increase.

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Physical Examination

The following physical findings may be noted:

  • Glossitis suggests that the macrocytosis stems from deficiency of vitamin B-12, folate, or both
  • Tachycardia is usually modest and is common in patients with severe anemia
  • Flow murmurs usually are noted only in patients with severe anemia
  • Splenomegaly may be quite remarkable when the macrocytosis is due to hemolysis, infiltrative disorders, or neoplasms
  • Jaundice suggests liver disease or hemolysis, both of which may lead to an increased MCV
  • Conjunctival pallor is evident in patients with severe anemia
  • Neurologic disorders, such as ataxia, loss of posterior column sensations, loss of deep tendon reflexes (particularly ankle reflex), and confabulation, may suggest thiamine deficiency
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Contributor Information and Disclosures
Author

Joseph E Maakaron, MD  Research Fellow, Department of Internal Medicine, American University of Beirut, Lebanon

Disclosure: Nothing to disclose.

Coauthor(s)

Ali Taher, MD  Professor of Medicine, Division of Hematology and Oncology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Russell Burgess, MD (Retired) Chief, Division of Hematology/Oncology, Eastern Carolina Internal Medicine, PA

Russell Burgess, MD is a member of the following medical societies: American College of Physicians and American Medical Association

Disclosure: Nothing to disclose.

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

References

  1. Kaferle J, Strzoda CE. Evaluation of macrocytosis. Am Fam Physician. Feb 1 2009;79(3):203-8. [Medline].

  2. Argento V, Roylance J, Skudlarska B, et al. Anemia prevalence in a home visit geriatric population. J Am Med Dir Assoc. Jul 2008;9(6):422-6. [Medline].

  3. Rumsey SE, Hokin B, Magin PJ, Pond D. Macrocytosis--an Australian general practice perspective. Aust Fam Physician. Jul 2007;36(7):571-2. [Medline]. [Full Text].

  4. Sternfeld T, Lorenz A, Schmid M, et al. Increased red cell corpuscular volume and hepatic mitochondrial function in NRTI-treated HIV infected patients. Curr HIV Res. May 2009;7(3):336-9. [Medline].

  5. Wu A, Chanarin I, Levi AJ. Macrocytosis of chronic alcoholism. Lancet. May 4 1974;1(7862):829-31. [Medline].

  6. Grgic I, Kaistha BP, Paschen S, Kaistha A, Busch C, Si H, et al. Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly. Pflugers Arch. Jun 2009;458(2):291-302. [Medline].

  7. Weinblatt ME, Fraser P. Elevated mean corpuscular volume as a predictor of hematologic toxicity due to methotrexate therapy. Arthritis Rheum. Dec 1989;32(12):1592-6. [Medline].

  8. Sechi LA, De Carli S, Catena C, Zingaro L, Bartoli E. Benign familial macrocytosis. Clin Lab Haematol. Mar 1996;18(1):41-3. [Medline].

  9. Bessman JD, Banks D. Spurious macrocytosis, a common clue to erythrocyte cold agglutinins. Am J Clin Pathol. Dec 1980;74(6):797-800. [Medline].

  10. Field EA, Speechley JA, Rugman FR, Varga E, Tyldesley WR. Oral signs and symptoms in patients with undiagnosed vitamin B12 deficiency. J Oral Pathol Med. Nov 1995;24(10):468-70. [Medline].

  11. Ellaway C, Christodoulou J, Kamath R, Carpenter K, Wilcken B. The association of protein-losing enteropathy with cobalamin C defect. J Inherit Metab Dis. Feb 1998;21(1):17-22. [Medline].

  12. Fernando OV, Grimsley EW. Prevalence of folate deficiency and macrocytosis in patients with and without alcohol-related illness. South Med J. Aug 1998;91(8):721-5. [Medline].

  13. Curtis D, Sparrow R, Brennan L, Van der Weyden MB. Elevated serum homocysteine as a predictor for vitamin B12 or folate deficiency. Eur J Haematol. Apr 1994;52(4):227-32. [Medline].

  14. 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. Jun 1990;34(2):99-107. [Medline].

  15. Phekoo K, Williams Y, Schey SA, Andrews VE, Dudley JM, Hoffbrand AV. Folate assays: serum or red cell?. J R Coll Physicians Lond. May-Jun 1997;31(3):291-5. [Medline].

  16. Ganji V, Kafai MR. Hemoglobin and hematocrit values are higher and prevalence of anemia is lower in the post-folic acid fortification period than in the pre-folic acid fortification period in US adults. Am J Clin Nutr. Jan 2009;89(1):363-71. [Medline].

 
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