Anemia

Diagnosis

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)
    • Normocytic, normochromic – suggests hypoproliferation
      • Consider the following
        • Bone marrow disorder
        • Inflammation
        • Autoimmune disease (eg, SLE)
        • Chronic renal disease
        • Critical illness
        • Chronic endocrine disorders (eg, thyroid disease)
        • Aplastic anemia, pure red cell aplasia
    • Microcytic, hypochromic – suggests maturation defects
      • Consider the following
        • Iron deficiency
        • Chronic disease – autoimmune disease, celiac disease, inflammatory bowel disease
        • Thalassemia
        • Sideroblastic anemia
        • Lead toxicity
    • Macrocytic – suggests maturation defects
      • Consider the following
        • Folate, B₁₂ deficiency
        • Drug effect
        • Alcohol abuse
        • Hypothyroidism
        • Myelodysplasia
    • Peripheral smear may give clues to the nature of anemia
      • Hypersegmented neutrophils suggest megaloblastic anemia
      • Fragmented RBCs (schistocytes, helmet cells) suggest hemolytic disease
      • RBC pallor suggests microcytic anemia
      • Teardrops in RBCs suggest myelofibrosis
      • Burr cells seen in liver disease
  • Reticulocyte count
    • Elevated in hemolytic etiologies – consider further testing based on history and clinical presentation
• Further testing based on 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
      • 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
  • 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

Screening

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

Epidemiology

• 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

Classification

• Based on morphology of red blood cell (RBC)
  • Mean cell volume (MCV)
    • Low MCV – microcytic
    • Normal MCV – normocytic
    • High MCV – 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

• Macrocytic
  • Drug effect (hydroxyurea, azido-thymidine)
  • Nutrient deficiency – folate, B₁₂
  • Hemolytic anemia
  • Hypothyroidism
  • Alcohol abuse
  • Myelodysplasia
• Normocytic
  • Acute blood loss
  • Hemolysis
  • Renal insufficiency
  • Chronic disease – inflammatory or malignant
  • Bone marrow infiltration – leukemia/lymphoma, metastatic disease, granulomatous disease
  • Hemoglobinopathies
• Microcytic
  • Iron deficiency
  • Chronic disease (inflammatory or malignant) occurs in a minority of the cases
  • Thalassemia

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 depend on etiology
  • Angular stomatitis, glossitis – iron or B₁₂ deficiency
  • Splenomegaly – hemolytic anemia
  • Vitiligo – pernicious anemia
  • Splinter hemorrhage in nails – chronic infection (endocarditis)

Treatment

• Based on diagnosis
• Acute loss may require transfusion to maintain circulation

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
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

Diagnostic Algorithm

  Anemia Testing Algorithm