What is anemia and how is it diagnosed and treated?

Anemia: Diagnosis and Management

Anemia is defined as a reduction of hemoglobin concentration below normal levels (less than 13 g/dL in men and less than 12 g/dL in women) and requires a systematic diagnostic approach followed by targeted treatment based on the underlying cause. 1

Classification and Diagnosis

• Anemia can be classified morphologically based on mean corpuscular volume (MCV) as microcytic (MCV < 80 fL), normocytic (MCV 80-100 fL), or macrocytic (MCV > 100 fL), which guides the diagnostic approach 1, 2

• Initial evaluation should include complete blood count with reticulocyte count, which helps differentiate between anemia due to decreased production (low reticulocytes) versus increased destruction or blood loss (high reticulocytes) 1

• For microcytic anemia, key diagnostic tests include serum ferritin, transferrin saturation, and C-reactive protein; a serum ferritin <30 μg/L indicates iron deficiency in the absence of inflammation 3

• In the presence of inflammation, serum ferritin up to 100 μg/L may still be consistent with iron deficiency 3

• A low MCV with elevated RDW (>14.0%) suggests iron deficiency anemia, while low MCV with normal RDW (≤14.0%) suggests thalassemia minor 2

• For suspected genetic disorders causing microcytic anemia, bone marrow examination may reveal ring sideroblasts or other characteristic findings 3

Differential Diagnosis

• Iron deficiency anemia: characterized by low serum ferritin, low transferrin saturation, and increased total iron-binding capacity 2, 4

• Anemia of chronic disease: associated with normal or elevated ferritin, low transferrin saturation, and elevated inflammatory markers (CRP, ESR) 5

• Genetic disorders affecting iron metabolism or heme synthesis: include defects in SLC11A2, STEAP3, SLC25A38, and ALAS2, which may present with microcytic hypochromic anemia and varying levels of systemic iron loading 3

• Thalassemias: characterized by microcytosis with normal or elevated RBC count and minimal anemia 3, 2

• Combined deficiencies: iron deficiency may coexist with vitamin B12 or folate deficiency, neutralizing the MCV changes 3

Treatment Approach

• The treatment of anemia should be directed at the underlying cause, with iron supplementation as first-line therapy for iron deficiency anemia using ferrous sulfate 200 mg three times daily for at least three months after correction of anemia. 2

• For patients who cannot tolerate ferrous sulfate, alternative formulations include ferrous gluconate and ferrous fumarate; adding ascorbic acid can enhance iron absorption 2

• A good therapeutic response is defined as a hemoglobin rise ≥10 g/L within 2 weeks, which confirms iron deficiency 2

• For patients with malabsorption or intolerance to oral iron, intravenous iron should be considered, with an expected hemoglobin increase of at least 2 g/dL within 4 weeks 2

• For anemia of chronic disease, treatment should target the underlying condition while considering erythropoiesis-stimulating agents in selected cases 1, 5

• For genetic disorders:

  • ALAS2 defects (X-linked sideroblastic anemia): trial of pyridoxine (vitamin B6) 50-200 mg daily 2
  • SLC25A38 defects: hematopoietic stem cell transplantation is the only curative option 3
  • SLC11A2 defects: oral iron, erythropoietin, or erythrocyte transfusions based on individual needs 2

Monitoring and Follow-up

• Monitor hemoglobin concentration and red cell indices at three-month intervals for one year and then after another year 2

• For patients receiving multiple transfusions or long-term iron therapy, monitor for iron overload with serum ferritin and consider liver MRI in specific cases 2

• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up 2

• In cancer patients, regularly evaluate if anemia is related to the malignancy itself, its treatment, or associated renal disease 3, 1

• In patients with inflammatory bowel disease, regularly monitor iron, B12, and folate levels, and consider maintenance iron therapy to prevent recurrences 1

Special Considerations

• Avoid unnecessary blood draws, especially in critically ill patients, to prevent iatrogenic anemia 1

• In pregnancy, routine screening for anemia is recommended, with iron supplementation for prevention and treatment 1, 4

• Children should be screened for anemia at one year of age 4

• Men and postmenopausal women with iron deficiency anemia should undergo gastrointestinal endoscopy to rule out occult bleeding 4

• Consider combined deficiencies, as iron deficiency may coexist with B12 or folate deficiency, particularly in malnourished patients 2