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

Anemia: Assessment, Pharmacology, and Pathophysiology

Anemia is defined as a reduction of the hemoglobin concentration, red blood cell count, or packed cell volume below normal levels, classified as mild (Hb 10-11.9 g/dL), moderate (Hb 8-9.9 g/dL), or severe (Hb <8 g/dL). 1, 2

Pathophysiology

Anemia results from three primary mechanisms:

1. Decreased production of functional red blood cells:

   • Bone marrow failure or suppression
   • Nutritional deficiencies (iron, vitamin B12, folate)
   • Chronic disease/inflammation
   • Renal insufficiency (decreased erythropoietin)
   • Bone marrow infiltration by malignancy

2. Increased destruction of red blood cells:

   • Hemolysis (immune or non-immune mediated)
   • Mechanical destruction

3. Blood loss:

   • Acute hemorrhage
   • Chronic blood loss

The normal erythropoietic process involves specialized interstitial cells in the kidney cortex that sense hypoxia and produce erythropoietin. This hormone binds to receptors on erythroid colony-forming units (CFU-Es) in bone marrow, preventing apoptosis and allowing cell survival and division, ultimately increasing reticulocyte production and restoring normal red blood cell mass 1.

Assessment and Diagnosis

Laboratory Evaluation

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

Additional Testing Based on Clinical Suspicion

• Hemolysis workup (Coombs test, haptoglobin, LDH)
• Stool guaiac test or endoscopy for occult blood loss
• Bone marrow examination when indicated
• Hemoglobin electrophoresis for suspected hemoglobinopathies 1, 2

Classification by Mean Corpuscular Volume (MCV)

• Microcytic (MCV <80 fL): Iron deficiency, thalassemia, anemia of chronic disease, sideroblastic anemia
• Normocytic (MCV 80-100 fL): Acute blood loss, hemolysis, anemia of chronic disease, renal disease
• Macrocytic (MCV >100 fL): Vitamin B12/folate deficiency, liver disease, alcoholism, myelodysplastic syndromes

Pharmacological Management

Iron Deficiency Anemia

• Oral iron therapy: First-line treatment with ferrous sulfate 324 mg daily (providing 65 mg elemental iron)
• Continue treatment for 3-6 months to replenish iron stores even after hemoglobin normalizes
• Parenteral iron: Reserved for patients with malabsorption, intolerance to oral iron, or when rapid repletion is needed 2, 3

Anemia of Chronic Kidney Disease

• Erythropoiesis-stimulating agents (ESAs): Indicated for treatment of anemia due to CKD
• Starting dose: 50-100 Units/kg three times weekly (IV or SC)
• Target hemoglobin: Avoid exceeding 11 g/dL due to increased cardiovascular risks
• Monitor hemoglobin weekly until stable, then monthly
• Supplemental iron therapy when serum ferritin <100 mcg/L or transferrin saturation <20% 4

Chemotherapy-Induced Anemia

• ESAs: Consider for patients with Hb ≤10 g/dL receiving chemotherapy
• Not indicated for patients receiving chemotherapy with curative intent
• Not indicated when anemia can be managed by transfusion
• Discontinue following completion of chemotherapy course
• Target hemoglobin: <12 g/dL to avoid thromboembolic complications 1, 4

Red Blood Cell Transfusions

• Consider for patients with:
  • Hemodynamic instability
  • Significant symptoms
  • Cardiovascular disease with poor tolerance of anemia
  • Severe anemia (Hb <8 g/dL) 2, 5

Special Considerations

Cancer-Related Anemia

• Prevalence: 40% of patients with non-myeloid malignancies
• Distribution: 30% mild, 9% moderate, 1% severe
• Incidence during chemo/radiotherapy: 54% overall
• Highest in lung (71%) and gynecological (65%) cancers
• Increases with number of chemotherapy cycles 1, 2

Anemia in Elderly

• Often multifactorial: nutritional deficiency (1/3), chronic disease (1/3), unexplained (1/3)
• "Unexplained anemia" may be due to erythropoietin resistance and chronic subclinical inflammation 6

Clinical Impact

Anemia has a significant negative impact on:

• Quality of life
• Exercise tolerance
• Cognitive function
• Cardiovascular function
• Overall survival in most cancer types 1, 2

Pitfalls and Caveats

1. Avoid treating numbers alone: Consider clinical symptoms and underlying cause before initiating treatment.

2. ESA risks: ESAs increase risks of death, serious cardiovascular reactions, and stroke when targeting Hb >11 g/dL. Use the lowest effective dose.

3. Iron supplementation: Always evaluate iron status before and during ESA therapy, as the majority of CKD patients will require supplemental iron.

4. Unexplained anemia: Never assume iron deficiency without proper workup; approximately one-third of anemia cases in elderly patients remain unexplained after standard evaluation.

5. Transfusion decisions: Balance the risks of anemia against the risks of transfusion (iron overload, infection transmission, immune suppression) when making transfusion decisions 4, 5.