What is anemia, including its assessment, pharmacology, and pathophysiology?

Anemia: Assessment, Pathophysiology, and Pharmacology

Anemia is defined as a reduction of hemoglobin concentration, red blood cell count, or packed cell volume below normal levels (Hb <12.0 g/dL in women and <13.0 g/dL in men), classified as mild (Hb 10-11.9 g/dL), moderate (Hb 8-9.9 g/dL), or severe (Hb <8 g/dL). 1

Pathophysiology

Anemia develops through several key mechanisms:

• Disrupted erythropoiesis: Normal red blood cell production involves specialized interstitial cells in the kidney cortex that sense hypoxia and produce erythropoietin. This hormone binds to receptors on erythroid colony-forming units in bone marrow, preventing apoptosis and allowing cell survival and division, ultimately increasing reticulocyte production 1

• Classification by red cell morphology:

  • Microcytic (MCV <80 fL): Typically iron deficiency, thalassemia
  • Normocytic (MCV 80-100 fL): Often anemia of chronic disease, acute blood loss
  • Macrocytic (MCV >100 fL): Usually vitamin B12 or folate deficiency 1

• Underlying mechanisms:

  • Decreased production of red blood cells
  • Increased destruction of red blood cells
  • Blood loss
  • Defective plasma iron transport (rare) 2

Assessment and Diagnosis

Laboratory Evaluation

1. Initial testing:

   • Complete blood count with reticulocyte count
   • Peripheral blood smear examination
   • Iron studies (serum iron, ferritin, transferrin saturation)
   • Vitamin B12 and folate levels
   • Renal function tests
   • C-reactive protein to assess inflammation 1

2. Morphological assessment:

   • Hypochromia, microcytosis, and marked anisocytosis suggest iron deficiency anemia 2
   • MCV helps classify the type of anemia 1

3. Severity grading:

   Grade	Hemoglobin Level
   0	Within normal limits
   1	Mild (Hb 10-11.9 g/dL)
   2	Moderate (Hb 8-9.9 g/dL)
   3	Severe (Hb <8 g/dL)
   4	Life-threatening
   5	Death

Clinical Presentation

• Mild anemia: Often asymptomatic
• Moderate anemia: Poor appetite, fatigue, lassitude, lethargy, exercise intolerance, irritability, dizziness
• Severe anemia: Tachycardia, shortness of breath, diaphoresis, poor capillary refill
• Chronic presentation: Worsening fatigue, dyspnea, lightheadedness, chest pain
• Acute presentation: Symptoms related to acute blood loss 3, 2

Pharmacological Management

Iron Deficiency Anemia

• First-line treatment: Oral ferrous sulfate 324 mg daily (providing 65 mg elemental iron) 1
• Optimal dosing for children: 3-6 mg/kg of elemental iron per day 2
• Duration: Continue treatment for 3-6 months after hemoglobin normalization to replenish iron stores
• Common side effects: Nausea, vomiting, constipation, stomach pain 4

Erythropoiesis-Stimulating Agents (ESAs)

• Indications:

  • Anemia due to chronic kidney disease
  • Anemia due to zidovudine in HIV patients
  • Chemotherapy-induced anemia in non-myeloid malignancies 5

• Dosing:

  • Starting dose: 50-100 Units/kg three times weekly (IV or SC)
  • Target hemoglobin: <11 g/dL to minimize cardiovascular risks 1, 5

• Limitations:

  • Not indicated when anticipated outcome is cure
  • Not indicated when anemia can be managed by transfusion
  • Not shown to improve quality of life or fatigue 5

• Monitoring:

  • Evaluate iron status before and during treatment
  • Monitor hemoglobin weekly until stable, then monthly
  • Adjust dose no more frequently than every 4 weeks 5

Blood Transfusions

• Indications:

  • Severe anemia (Hb <8 g/dL)
  • Hemodynamic instability
  • Significant symptoms
  • Cardiovascular disease with poor tolerance of anemia 1

• Considerations:

  • Decisions should be individualized based on patient factors (age, comorbidities)
  • Physiologic variables should be considered alongside hemoglobin values 6

Special Considerations

Anemia in Elderly

• Definition: Hb <12 g/dL in both sexes
• Often multifactorial: nutritional deficiency (1/3), chronic disease (1/3), unexplained (1/3)
• Contributes significantly to morbidity and mortality 7

Anemia in Cancer Patients

• Prevalence: 40% of patients with non-myeloid malignancies
• Distribution: 30% mild, 9% moderate, 1% severe
• Negative impact on quality of life, exercise tolerance, cognitive function, cardiovascular function, and overall survival 1

Pediatric Anemia

• Most common in children aged 9 months to 3 years and during adolescence
• Screening: Universal laboratory screening at approximately 1 year of age
• Neurodevelopmental impact: Severe and prolonged iron deficiency anemia can result in cognitive deficits that may not be fully reversible 2

Common Pitfalls and Caveats

1. Treating numbers alone: Always consider clinical symptoms and underlying cause before initiating treatment 1

2. Overlooking iron status: Evaluate iron stores before and during treatment; supplement when serum ferritin is <100 mcg/L or transferrin saturation is <20% 5

3. ESA overuse: Use the lowest effective dose to avoid serious cardiovascular and thromboembolic reactions 5

4. Ignoring multifactorial causes: Anemia is often not an independent phenomenon; evaluate for underlying conditions 7

5. Missing occult blood loss: Always assess for occult bleeding, especially in iron deficiency anemia 1

6. Inadequate follow-up: Continue monitoring even after initiating therapy to ensure appropriate response 1