What are the causes and treatments of anemia?

Causes and Treatments of Anemia

Anemia is caused by decreased red blood cell production, increased destruction, or blood loss, and treatment should target the specific underlying cause while considering patient factors, disease characteristics, and treatment-related considerations. 1

Definition and Classification

Anemia is defined as a reduction in hemoglobin concentration, red cell count, or packed cell volume below normal levels, with severity classified as:

• Mild: Hemoglobin ≤11.9 g/dL and ≥10 g/dL
• Moderate: Hemoglobin ≤9.9 g/dL and ≥8.0 g/dL
• Severe: Hemoglobin <8.0 g/dL 1

Causes of Anemia

Decreased Production of Red Blood Cells

• Nutritional deficiencies:

  • Iron deficiency (most common cause of microcytic anemia) 2, 3
  • Vitamin B12 and folate deficiencies (causing macrocytic anemia) 2
  • Note: Folate deficiency has decreased significantly since food fortification began 1

• Bone marrow disorders:

  • Bone marrow infiltration by cancer 1
  • Myelodysplastic syndromes 2
  • Aplastic anemia 1

• Chronic conditions:

  • Anemia of chronic disease/inflammation 1
  • Renal insufficiency (decreased erythropoietin production) 1
  • Endocrine disorders (thyroid disease) 2

Increased Destruction of Red Blood Cells

• Hemolytic anemias:

  • Autoimmune hemolytic anemia (common in chronic lymphocytic leukemia) 1
  • Drug-induced hemolysis 1
  • Microangiopathic processes 1
  • Genetic disorders (thalassemias, G6PD deficiency, sickle cell disease) 4, 5

• Hypersplenism:

  • Sequestration of red blood cells in enlarged spleen 1
  • Common in myeloproliferative disorders and lymphoid malignancies 1

Blood Loss

• Acute hemorrhage:

  • Trauma or surgery 1
  • Gastrointestinal bleeding 3

• Chronic blood loss:

  • Gastrointestinal ulcerations 3
  • Malignancies (60-70% of patients with iron deficiency anemia have GI source when referred for endoscopy) 2, 3
  • Gynecological causes (menorrhagia) 5

• Treatment-related causes:

  • Chemotherapy-induced myelosuppression 1
  • Radiation therapy 1
  • Frequent phlebotomy for laboratory testing 1

Diagnostic Approach

Initial Evaluation

• Complete blood count with reticulocyte count 1
• Peripheral blood smear examination 1
• Iron studies (iron, transferrin saturation, ferritin) 1
• Vitamin B12 and folate levels (if macrocytic) 1
• C-reactive protein (to assess inflammation) 1
• Renal function tests 1
• Assessment for occult blood loss (stool and urine) 1

Morphologic Classification

• Microcytic anemia (MCV <80 fL): Consider iron deficiency, thalassemia, anemia of chronic disease 1
• Normocytic anemia (MCV 80-100 fL): Consider hemorrhage, hemolysis, bone marrow failure, chronic inflammation 1
• Macrocytic anemia (MCV >100 fL): Consider vitamin B12/folate deficiency, alcoholism, medications, myelodysplastic syndromes 1, 2

Special Tests

• Coombs testing for suspected hemolytic anemia (especially in chronic lymphocytic leukemia, non-Hodgkin's lymphoma, or history of autoimmune disease) 1
• Endogenous erythropoietin levels in suspected myelodysplasia 1
• Bone marrow examination when indicated 1
• Endoscopy for iron deficiency anemia without obvious cause 3

Treatment Approaches

Treating Underlying Causes

• Iron deficiency:

  • Oral iron supplementation: 100-200 mg elemental iron daily (lower dose if side effects occur) 3
  • Treatment duration: 3-6 months to normalize hemoglobin and replenish iron stores 3
  • Parenteral iron for oral intolerance, malabsorption, or inflammation 2, 3

• Vitamin deficiencies:

  • Vitamin B12 supplementation (oral can be as effective as intramuscular) 2
  • Folate supplementation 2

• Anemia in cancer patients:

  • Erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia with Hb ≤10 g/dL 1
  • Initial ESA dosing: 40,000 units weekly or 150 units/kg three times weekly 6
  • Monitor response after 4 weeks; adjust dose based on hemoglobin response 1
  • Discontinue ESAs 4 weeks after completing chemotherapy 1
  • Important safety considerations: ESAs increase risk of thromboembolism, cardiovascular events, and may promote tumor growth 6

• Blood transfusions:

  • For severe symptomatic anemia or when rapid correction is needed 1
  • Consider risks including iron overload, infection transmission, and immune suppression 1

Special Considerations

• For unexplained iron deficiency anemia, evaluate for GI malignancy with bidirectional endoscopy (except in premenopausal women <40 years) 3
• In patients with genetic disorders (thalassemia, G6PD deficiency), education and genetic counseling are important 4, 5
• For anemia of chronic disease, treat the underlying inflammatory condition 1

Pitfalls and Caveats

• Do not use ESAs in cancer patients not receiving chemotherapy due to increased mortality risk 1
• Do not target hemoglobin >12 g/dL with ESAs due to increased cardiovascular risks 1, 6
• Do not assume iron deficiency is the only cause of anemia; multiple etiologies often coexist 1, 7
• Do not overlook gastrointestinal sources of blood loss in iron deficiency anemia 2, 3
• Consider functional iron deficiency (ferritin >100 ng/mL but transferrin saturation <20%) when evaluating response to ESAs 1