What are the differences in types, causes, and treatments of anemias, particularly in different patient demographics and underlying health conditions?

Differences in Anemias: Classification, Causes, and Treatment

Morphologic Classification by MCV

Anemias are best differentiated initially by mean corpuscular volume (MCV), which divides them into three categories with distinct etiologies and management approaches. 1

Microcytic Anemia (MCV <80 fL)

• Most commonly caused by iron deficiency, which accounts for approximately one-half of all anemia cases worldwide 1, 2
• Other causes include thalassemia, anemia of chronic disease, and sideroblastic anemia 1
• Diagnostic confirmation requires low iron stores (ferritin <30 ng/mL, transferrin saturation <15%) and hemoglobin two standard deviations below normal 1, 2
• In men and postmenopausal women, iron deficiency anemia mandates gastrointestinal evaluation with endoscopy to exclude malignancy 1, 2

Normocytic Anemia (MCV 80-100 fL)

• May result from hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency 1
• The reticulocyte index (RI) is the critical follow-up test to distinguish production defects from destruction/loss 1
• Low RI (<1.0) indicates decreased RBC production from iron deficiency, vitamin B12/folate deficiency, aplastic anemia, or bone marrow dysfunction 1
• High RI (>2.0) indicates normal/increased production with blood loss or hemolysis 1

Macrocytic Anemia (MCV >100 fL)

• Most macrocytic anemia is megaloblastic, indicating vitamin B12 or folate deficiency from insufficient uptake or inadequate absorption through lack of intrinsic factor 1
• Non-megaloblastic causes include alcoholism, myelodysplastic syndromes, and certain drugs (hydroxyurea, diphenytoin) 1
• Diagnosis confirmed by low vitamin B12 or folate levels 1

Key Diagnostic Distinctions

Absolute vs. Functional Iron Deficiency

• Absolute iron deficiency: ferritin <100 ng/mL with transferrin saturation <15% 1
• Functional iron deficiency: transferrin saturation <20% with ferritin ≥100 ng/mL, indicating inadequate iron mobilization despite adequate stores 1
• This distinction is critical in cancer patients receiving chemotherapy, where functional iron deficiency may require intravenous iron even with normal ferritin 1

Hemolytic Anemia Markers

• Positive Coombs test, positive disseminated intravascular coagulation panel, low haptoglobin levels, and elevated indirect bilirubin distinguish hemolysis 1
• Clinical signs include jaundice, splenic enlargement, and petechiae 1

Treatment Differences by Etiology

Iron Deficiency Anemia

Oral iron supplementation (ferrous sulfate 324 mg daily or twice daily between meals) is first-line therapy 3, 4, 5

• Continue treatment for 2-3 months after hemoglobin normalization to replenish iron stores 3, 4, 5
• Intravenous iron is indicated when oral iron is not tolerated, malabsorption is present, or rapid repletion is needed 1, 3, 4
• In inflammatory bowel disease with active inflammation, intravenous iron is preferred over oral 1, 3

Cancer and Chemotherapy-Induced Anemia

Erythropoiesis-stimulating agents (ESAs) should only be considered in symptomatic patients receiving chemotherapy with hemoglobin <10 g/dL after correcting iron deficiency 1, 6

• Target hemoglobin is 12 g/dL without transfusions 1
• ESAs are NOT indicated in patients not receiving chemotherapy, those receiving hormonal agents or radiotherapy alone, or when cure is the anticipated outcome 6
• ESAs carry significant risks including hypertension, thromboembolism, and potential tumor progression 4, 5
• Dosing: darbepoetin alfa 2.25 mcg/kg weekly or 500 mcg every 3 weeks 1, 6

Anemia of Chronic Disease/Inflammation

• Treat the underlying inflammatory condition to enhance iron absorption 3, 5
• Intravenous iron therapy is recommended when functional iron deficiency is present (transferrin saturation <20%) 1
• ESAs may be considered in specific situations but are not first-line 3

Genetic Disorders of Iron Metabolism

• Sideroblastic anemia due to SLC25A38 defects presents with severe transfusion-dependent microcytic anemia in childhood 1
• Bone marrow shows ring sideroblasts with elevated ferritin and transferrin saturation even before transfusions 1
• Hematopoietic stem cell transplantation is the only curative treatment 1
• Anemia with systemic iron loading from DMT1 defects requires careful management as transfusions and iron supplementation cause additional liver iron loading 1

Transfusion Thresholds by Population

Use restrictive transfusion strategy (hemoglobin trigger 7-8 g/dL) in hospitalized patients, including those with coronary heart disease 1, 3, 4

• Reserve transfusion for severe symptomatic anemia or when rapid correction is needed 4, 5
• Potential complications include iron overload, infection transmission, immune suppression, pulmonary embolism, and increased mortality 1, 4

Perioperative Anemia Management

In patients with iron deficiency anemia having elective surgery, preoperative iron therapy (oral or intravenous) is reasonable to reduce transfusions and increase hemoglobin 1

• Tranexamic acid is reasonable to reduce intraoperative blood loss and avoid anemia 1
• Even mild preoperative anemia (hemoglobin <13 g/dL in men, <12 g/dL in women) is an independent risk factor for postoperative morbidity and mortality 1

Critical Pitfalls to Avoid

• Failure to investigate gastrointestinal blood loss in men and postmenopausal women with iron deficiency anemia can miss malignancy 1, 3
• Using ESAs without first correcting iron deficiency reduces efficacy and increases risks 1
• Continuing ESAs in non-responders after 4-8 weeks wastes resources and exposes patients to unnecessary risks 1
• Overlooking functional iron deficiency in cancer patients receiving chemotherapy leads to suboptimal anemia management 1
• Transfusing based solely on hemoglobin thresholds without considering symptoms and comorbidities increases complications 1