Anemia Management

Definition and Diagnosis

• Anemia is defined as a hemoglobin concentration below 12.0 g/dL in non-pregnant women over 15 years of age, and below 11.0 g/dL in pregnant women, according to the World Health Organization 1
• The lower limit of the normal range for the specific laboratory performing the test can be used to define anemia, as normal hemoglobin ranges may vary between different populations and laboratories 1
• Anemia can be classified into three main categories: microcytic, normocytic, and macrocytic, based on the mean corpuscular volume (MCV), with specific diagnostic criteria for each category 2, 3
• A complete blood count (CBC) with indices, reticulocyte count, peripheral blood smear examination, and targeted testing based on the morphologic classification and reticulocyte response should be performed to diagnose the underlying cause of anemia 2

Iron Deficiency Anemia

• Iron deficiency anemia is characterized by low serum iron, high total iron-binding capacity (TIBC), and low ferritin levels, with the following key differences from anemia of chronic disease:

• All patients with iron deficiency anemia should receive iron supplementation to correct anemia and replenish body stores 1
• Ferrous sulfate 325 mg daily or on alternate days is recommended as first-line treatment for most patients with iron deficiency anemia, with treatment continuing for 3-6 months after normalization of hemoglobin to replenish stores, as recommended by the American Gastroenterological Association 5, 6

Anemia of Chronic Disease

• Anemia of chronic disease is characterized by impaired iron utilization due to inflammatory cytokines, increased hepcidin production causing iron sequestration in macrophages, reduced iron absorption from the gut, shortened red blood cell lifespan, and blunted erythropoietin response, with laboratory findings typically including normal or elevated ferritin, low transferrin saturation, normal MCV, low reticulocyte count, and evidence of underlying inflammatory condition 2
• The American Gastroenterological Association recommends treating the underlying inflammatory condition rather than focusing solely on iron supplementation for anemia of chronic disease, and iron supplementation should only be considered if concurrent iron deficiency is confirmed 7, 8

Erythropoiesis-Stimulating Agents (ESAs)

• ESAs may be considered if inadequate response to iron alone, with a target Hb of 10-11 g/dL, and monitoring of Hb every 2-4 weeks initially, then monthly, as recommended by the National Kidney Foundation 9, 10
• ESAs increase the risk of venous thromboembolism (VTE) 1.5-fold, and should be used with caution in patients being treated with curative intent due to concerns about tumor progression, as advised by the American Society of Clinical Oncology 11, 12

Chronic Kidney Disease (CKD)-Associated Anemia

• The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines define iron deficiency in CKD as transferrin saturation ≤30% and ferritin ≤500 ng/ml in non-dialysis CKD patients 9
• Iron supplementation with ferrous sulfate 325 mg twice daily is the most appropriate treatment for patients with CKD-associated anemia and iron deficiency, according to the KDIGO guidelines 9
• Oral iron therapy is appropriate for non-dialysis CKD patients, and reassessing hemoglobin and iron studies after 1-3 months of therapy is recommended 9
• If oral iron therapy fails, consider intravenous iron, and if iron repletion alone is insufficient, consider ESAs 9

Monitoring and Adjunctive Therapies

• Continue iron supplementation throughout ESA therapy, and monitor iron indices regularly to ensure adequate iron availability for erythropoiesis, as recommended by the British Society of Anaesthetists 13
• Ferritin is an acute phase reactant and may be elevated despite iron deficiency, so consider the entire clinical picture and all iron indices, according to the European Society of Gastrointestinal Endoscopy 6
• Intravenous iron should be considered, especially if iron saturation <20% and ferritin <100 μg/L, or if the patient is symptomatic from anemia, or if rapid correction is needed, as suggested by the British Society of Anaesthetists 13 and the European Society of Gastrointestinal Endoscopy 6

Vitamin B12 and Folate Deficiency

• Patients with inflammatory bowel disease or other chronic conditions require closer surveillance, and vitamin B12 and folate levels should be measured at least annually, or if macrocytosis is present, as recommended by the European Crohn's and Colitis Organisation 2
• Serum folate levels less than 3 ng/mL or RBC folate levels less than 140 ng/mL suggest folate deficiency, and measuring both B12 and folate levels simultaneously is recommended as deficiencies can coexist, according to Clinical Nutrition guidelines 14
• Including homocysteine measurement can improve interpretation of B12 and folate levels 14
• Before treating folate deficiency, it is essential to rule out B12 deficiency first, as treating folate deficiency alone may mask B12 deficiency and precipitate subacute combined degeneration of the spinal cord, according to Obesity Reviews and Clinical Nutrition guidelines 14, 15
• For B12 deficiency with neurological involvement, the American College of Nutrition recommends administering hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then maintaining with hydroxocobalamin 1 mg intramuscularly every 2 months lifelong, and seeking urgent specialist advice from neurologist and hematologist 15
• For B12 deficiency without neurological involvement, hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, then maintaining with 1 mg intramuscularly every 2-3 months lifelong is recommended 15
• For confirmed folate deficiency, administering oral folic acid 5 mg daily for a minimum of 4 months and investigating potential causes of deficiency is recommended 14, 15