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Indications for Testing

  • Symptoms of anemia (eg, fatigue, weakness, pallor, dizziness, fainting)

Laboratory Testing

  • Initial evaluation – CBC with red blood cell indices and possibly peripheral smear with cell morphology
    • Classify by indices (normocytic, macrocytic, microcytic)
      • Normocytic, normochromic – suggests hypoproliferation
      • Microcytic, hypochromic – suggests maturation defects
      • Macrocytic – suggests maturation defects
      • Peripheral smear may be helpful in diagnosis
    • Reticulocyte count
      • Elevated in hemolytic disease states – consider further hemolytic evaluation based on history and clinical presentation
  • Further testing using results of CBC and reticulocyte count
    • Normocytic or normochromic; microcytic or hypochromic
      • Iron and iron binding capacity, ferritin
        • Low/normal total iron binding capacity (TIBC), normal/high ferritin, low/normal iron – inflammation, chronic disease
          • If no obvious chronic disease present, consider bone marrow biopsy
          • If suspicion for thalassemia, consider hemoglobin electrophoresis
        • High TIBC, low iron, low ferritin
          • Iron deficiency, anemia
    • Macrocytic
      • B12
      • Folate testing
        • Unless patient is at high risk for folate deficiency, do not test – folate deficiency is uncommon in U.S.
        • If testing only for folate deficiency (usually not recommended), use RBC folate
    • If abnormal peripheral smear, further testing based on smear characteristics (regardless of indices)
      • Bone marrow biopsy may be necessary

Differential Diagnosis

  • See Morphologic Etiology in Clinical Background for differential diagnoses
  • Annual CBC testing is appropriate for patients with chronic comorbidity
  • In the absence of chronic comorbidity, CBC testing is appropriate every 5 years in all females, men >50 years, and patients with anemia signs and symptoms

Anemia is characterized by decreased red blood cell mass, causing symptoms resulting from tissue hypoxia.

Definition (World Health Organization)

  • All definitions are sea-level measurements
    • Males ≥18 years – hemoglobin <13 g/dL
    • Nonpregnant females ≥18 years – hemoglobin <12 g/dL


  • Incidence
    • Females – 29-30/1,000
    • Males – 6/1,000 for <45 years; 18.5/1,000 for >75 years
  • Age – different peaks depending on etiology of anemia
  • Sex – M<F during childbearing years


  • Based on morphology of red blood cell (RBC)
    • Mean cell volume (MCV)
      • Low MCV (<80)– microcytic
      • Normal MCV – normocytic
      • High MCV (>100) – macrocytic
    • Mean cell hemoglobin (MCH) and MCH concentration (MCHC)
      • Low MCH/MCHC – hypochromic
      • Normal MCH/MCHC – normochromic
  • Based on RBC production rate – measure of hemolysis
    • Measured by reticulocyte count
    • Reticulocyte count formula (with correction for anemia) – ReticCount% x (Hgb/Htc) x (1/maturation time correction*)
      • * Use 2% for most patients

Morphologic Etiology

Clinical Presentation

  • Acute loss – hypotension, tachycardia, confusion, diaphoresis
    • Obvious source of blood loss may initially be lacking
  • Chronic loss – fatigue, pallor, headache, dyspnea
    • Younger patients
      • Clinical symptoms may be absent until anemia is severe
      • Fatigue, pallor, dyspnea with strenuous exercise
      • Pica
    • Older patients –first manifestation may be angina, dyspnea
  • Other signs and symptoms (etiology based)
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Reticulocytes, Percent and Number 0040022
Method: Flow Cytometry

Iron and Iron Binding Capacity 0020420
Method: Quantitative Spectrophotometry

Ferritin 0070065
Method: Quantitative Chemiluminescent Immunoassay

Vitamin B12 0070150
Method: Quantitative Chemiluminescent Immunoassay

General References

Asare K. Anemia of critical illness. Pharmacotherapy. 2008; 28(10): 1267-82. PubMed

Bross MH, Soch K, Smith-Knuppel T. Anemia in older persons. Am Fam Physician. 2010; 82(5): 480-7. PubMed

Bryan LJ, Zakai NA. Why is my patient anemic? Hematol Oncol Clin North Am. 2012; 26(2): 205-30, vii. PubMed

Cullis JO. Diagnosis and management of anaemia of chronic disease: current status. Br J Haematol. 2011; 154(3): 289-300. PubMed

DeLoughery TG. Microcytic anemia. N Engl J Med. 2014; 371(14): 1324-31. PubMed

Goodnough LT, Schrier SL. Evaluation and management of anemia in the elderly. Am J Hematol. 2014; 89(1): 88-96. PubMed

Heidemann D, Baker-Genaw K, Joseph N, Kuriakose P. Increasing Cost Sensitivity in the Diagnostic Evaluation of Microcytic Anemia. 54(11);837-840. Consultant 360. [Accessed: Nov 2015]

Hussein M, Haddad RY. Approach to anemia. Dis Mon. 2010; 56(8): 449-55. PubMed

Janus J, Moerschel SK. Evaluation of anemia in children. Am Fam Physician. 2010; 81(12): 1462-71. PubMed

Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. Lancet. 2016; 387(10021): 907-16. PubMed

Van Vranken M. Evaluation of microcytosis. Am Fam Physician. 2010; 82(9): 1117-22. PubMed

Vieth JT, Lane DR. Anemia. Emerg Med Clin North Am. 2014; 32(3): 613-28. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Agarwal N, Prchal JT. Anemia of chronic disease (anemia of inflammation). Acta Haematol. 2009; 122(2-3): 103-8. PubMed

Auerbach M, Rodgers GM. Intravenous iron. N Engl J Med. 2007; 357(1): 93-4. PubMed

Gilreath JA, Stenehjem DD, Rodgers GM. Total dose iron dextran infusion in cancer patients: is it SaFe2+? J Natl Compr Canc Netw. 2012; 10(5): 669-76. PubMed

Laman CA, Silverstein SB, Rodgers GM. Parenteral iron therapy: a single institution's experience over a 5-year period. J Natl Compr Canc Netw. 2005; 3(6): 791-5. PubMed

Martin FM, Prchal J, Nieva J, Saven A, Andrey J, Bethel K, Barton JC, Aripally G, Bottomley SS, Friedman JS. Purification and characterization of sideroblasts from patients with acquired and hereditary sideroblastic anaemia. Br J Haematol. 2008; 143(3): 446-50. PubMed

Price E, Artz AS, Barnhart H, Sapp S, Chelune G, Ershler WB, Walston JD, Gordeuk VR, Berger NA, Reuben D, Prchal J, Rao SV, Roy CN, Supiano MA, Schrier SL, Cohen HJ. A prospective randomized wait list control trial of intravenous iron sucrose in older adults with unexplained anemia and serum ferritin 20-200 ng/mL. Blood Cells Mol Dis. 2014; 53(4): 221-30. PubMed

Rodgers GM, Becker PS, Bennett CL, Cella D, Chanan-Khan A, Chesney C, Cleeland C, Coccia PF, Djulbegovic B, Garst JL, Gilreath JA, Kraut EH, Lin W, Matulonis U, Millenson M, Reinke D, Rosenthal J, Sabbatini P, Schwartz RN, Stein RS, Vij R, Network NC. Cancer- and chemotherapy-induced anemia. J Natl Compr Canc Netw. 2008; 6(6): 536-64. PubMed

Rodgers GM. Guidelines for the use of erythropoietic growth factors in patients with chemotherapy-induced anemia. Oncology (Williston Park). 2006; 20(8 Suppl 6): 12-5. PubMed

Sheftel AD, Richardson DR, Prchal J, Ponka P. Mitochondrial iron metabolism and sideroblastic anemia. Acta Haematol. 2009; 122(2-3): 120-33. PubMed

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Last Update: August 2016