Indications for Testing

  • Patient with fatigue, weakness, pallor, dizziness, fainting

Laboratory Testing

  • Initial evaluation – CBC with red blood cell indices combined with cell morphology on peripheral smear
    • Classify by indices (normocytic, macrocytic, microcytic)
    • Reticulocyte count
      • Elevated in hemolytic disease states – consider further hemolytic evaluation based on history and clinical presentationn
  • 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
        • If testing only for folate deficiency (usually not recommended), use RBC folate
        • Unless patients is at high risk for folate deficiency, do not test – folate deficiency is uncommon in U.S.
    • If abnormal peripheral smear, workup 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

Clinical Background

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
    • May not have obvious source of blood loss at presentation
  • Chronic loss – fatigue, pallor, lack of stamina, breathlessness
    • Younger patients
      • May not have clinical symptoms until anemia is severe
      • Fatigue, pallor, dyspnea with strenuous exercise
      • Pica
    • Older patients – may first manifest with 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
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Identify presence of anemia; establish morphology indices

Reticulocytes, Percent & Number 0040022
Method: Flow Cytometry

Identify presence of immature RBCs and hemolysis as etiology of anemia

Iron and Iron Binding Capacity 0020420
Method: Quantitative Spectrophotometry

Aids in the diagnosis of iron deficiency, anemia

Ferritin 0070065
Method: Quantitative Chemiluminescent Immunoassay

Aids in the diagnosis of iron deficiency

Vitamin B12  0070150
Method: Quantitative Chemiluminescent Immunoassay

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

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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

Diagnostic Algorithm