• Diagnosis
  • Algorithms
  • Screening
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

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

Laboratory Testing

  • Initial evaluation – CBC with red blood cell indices AND 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 patients 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

Anemia Testing Algorithm

  • 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, lack of stamina, breathlessness
    • Younger patients
      • Clinical symptoms may be absent until anemia is severe
      • Fatigue, pallor, dyspnea with strenuous exercise
      • Pica
    • Older patients –first manifestion may be angina, dyspnea
  • Other signs and symptoms (etiology based)

Indications for Laboratory Testing

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

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Reticulocytes, Percent & 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

Additional Tests Available

Vitamin B12 and Folate 0070160
Method: Quantitative Chemiluminescent Immunoassay


Aids in detection of vitamin B12 and folate deficiency in individuals with macrocytic or unexplained anemia, or unexplained neurologic disease

Soluble Transferrin Receptor 0070283
Method: Quantitative Immunoturbidimetry

Transferrin, Serum 0050570
Method: Quantitative Immunoturbidimetry

Hemoglobin, Serum 0020057
Method: Quantitative Spectrophotometry

Hemoglobin 0040085
Method: Flow Cytometry

Manual Differential 0040005
Method: Microscopy

Hematocrit 0040080
Method: Automated Cell Count

Folate, RBC 0070385
Method: Quantitative Chemiluminescent Immunoassay

Iron, Plasma or Serum 0020037
Method: Quantitative Spectrophotometry

Vitamin B12 Deficiency Panel 2012276
Method: Quantitative Gas Chromatography/Mass Spectrometry 


Not recommended for initial testing in suspected B12 deficiency; may be useful when B12 and MMA results alone are equivocal

Panel includes methylmalonic acid, 2-methylcitric acid, homocysteine, and cystathionine

General References

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

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

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

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

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

Goodnough L, Schrier S. 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 R. Approach to anemia. Dis Mon. 2010; 56(8): 449-55. PubMed

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

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

Vieth J, Lane D. 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 J. Anemia of chronic disease (anemia of inflammation). Acta Haematol. 2009; 122(2-3): 103-8. PubMed

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

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

Laman C, Silverstein S, Rodgers G. 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 F, Prchal J, Nieva J, Saven A, Andrey J, Bethel K, Barton J, Aripally G, Bottomley S, Friedman J. 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 A, Barnhart H, Sapp S, Chelune G, Ershler W, Walston J, Gordeuk V, Berger N, Reuben D, Prchal J, Rao S, Roy C, Supiano M, Schrier S, Cohen H. 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 G, Becker P, Bennett C, Cella D, Chanan-Khan A, Chesney C, Cleeland C, Coccia P, Djulbegovic B, Garst J, Gilreath J, Kraut E, Lin W, Matulonis U, Millenson M, Reinke D, Rosenthal J, Sabbatini P, Schwartz R, Stein R, Vij R, Network N. Cancer- and chemotherapy-induced anemia. J Natl Compr Canc Netw. 2008; 6(6): 536-64. PubMed

Rodgers G. 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 A, Richardson D, Prchal J, Ponka P. Mitochondrial iron metabolism and sideroblastic anemia. Acta Haematol. 2009; 122(2-3): 120-33. PubMed

Medical Reviewers

Last Update: February 2016