What are the diagnostic steps and treatment options for anemia according to American Hematology guidelines?

Diagnostic Steps and Treatment Options for Anemia According to American Hematology Guidelines

The diagnostic approach to anemia requires systematic evaluation starting with hemoglobin levels below 135 g/L in adult males and below 120 g/L in adult females, followed by targeted testing based on red cell indices to determine the specific cause, and treatment tailored to the underlying etiology. 1

Diagnosis of Anemia

Initial Evaluation

• Anemia is defined as hemoglobin <135 g/L in males and <120 g/L in females ≥18 years of age 1
• These definitions may not apply to patients who are pregnant, menstruating, living at high altitude, smoking, elderly (≥70 years), non-Caucasian, have chronic lung disease, or hemoglobinopathy 1
• Complete blood count (CBC) with red cell indices is the first diagnostic test, offering important clues to the classification and cause of anemia 2, 3

Classification Based on Mean Corpuscular Volume (MCV)

• Microcytic anemia (MCV <80 fL): Consider iron deficiency, genetic disorders of iron metabolism, thalassemia 1
• Normocytic anemia (MCV 80-100 fL): Consider anemia of chronic disease, hemolysis, blood loss 2
• Macrocytic anemia (MCV >100 fL): Consider vitamin B12/folate deficiency, myelodysplastic syndrome, medications 2, 3

Additional Testing Based on Initial Classification

• For all types: Reticulocyte count to assess bone marrow response 2, 3

  • Low reticulocyte count: Decreased production
  • High reticulocyte count: Blood loss or hemolysis

• For microcytic anemia:

  • Iron studies (serum ferritin, iron, total iron-binding capacity, transferrin saturation) 3
  • If iron deficiency is excluded, consider hemoglobin electrophoresis for thalassemia 1
  • Genetic testing for rare disorders when appropriate (TF, SLC11A2, STEAP3 genes) 1

• For normocytic anemia:

  • Peripheral blood smear examination 2
  • If hemolysis suspected: LDH, haptoglobin, bilirubin, Coombs test 2, 3
  • Renal function tests to assess for anemia of chronic kidney disease 1

• For macrocytic anemia:

  • Vitamin B12 and folate levels 3
  • Liver function tests 2
  • Thyroid function tests 2

Treatment Options

Iron Deficiency Anemia

• First-line treatment: Oral ferrous sulfate 200 mg once daily 4

  • Once-daily dosing improves tolerance while maintaining effectiveness
  • Continue therapy for 3 months after correction of anemia to replenish iron stores
  • Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment

• Indications for intravenous iron:

  • Intolerance to oral iron despite trying at least two different preparations 4
  • Inadequate response to oral iron therapy after 4 weeks
  • Conditions affecting iron absorption (inflammatory bowel disease, celiac disease)
  • Severe anemia (Hb <10 g/dL) in inflammatory bowel disease

Vitamin B12 Deficiency

• For pernicious anemia: Intramuscular vitamin B12 100 mcg daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life 5
• For patients with normal intestinal absorption: Initial treatment similar to pernicious anemia based on severity, followed by oral B12 maintenance 5

Anemia in Cancer Patients

• For chemotherapy-associated anemia:
  • Consider erythropoiesis-stimulating agents (ESAs) when hemoglobin <10 g/dL in patients receiving palliative chemotherapy 1
  • ESAs are not indicated for patients receiving curative chemotherapy 1
  • Red blood cell transfusion is an option depending on severity and clinical circumstances 1
  • Monitor for risk of thromboembolism in patients receiving ESAs 1

Genetic Disorders of Iron Metabolism or Heme Synthesis

• For SLC11A2 defects: Oral iron supplementation, erythropoietin, and/or erythrocyte transfusions based on individual needs 1
• For STEAP3 defects: Erythrocyte transfusions with erythropoietin; iron chelation for systemic iron loading 1
• For SLC25A38 defects: Hematopoietic stem cell transplantation as curative option; symptomatic treatment with erythrocyte transfusions and chelation therapy 1
• For X-linked sideroblastic anemia (ALAS2 defects): Initial treatment with pyridoxine 50-200 mg daily; lifelong supplementation with 10-100 mg daily if responsive 1

Monitoring and Follow-up

• Hemoglobin and red cell indices should be monitored at 3-month intervals for the first year after correction, then again after another year 4
• For patients on ESAs, monitor hemoglobin weekly initially 1
• Consider evaluation for additional causes of anemia if inadequate response to initial treatment 1

Common Pitfalls to Avoid

• Failing to treat the underlying cause of anemia while supplementing iron 4
• Continuing oral iron despite poor tolerance or inadequate response 4
• Using multiple daily doses of oral iron, which increases side effects without improving efficacy 4
• Overlooking the need for vitamin C supplementation to enhance iron absorption 4
• Mistakenly assuming red cell transfusions reverse iron deficiency (transfused red cells have a lifespan of 100-110 days, and iron is not immediately available for erythropoiesis) 1