What is the appropriate treatment for a 76‑year‑old woman with a red blood cell count of 3.63 ×10⁶/µL and hemoglobin of 10.5 g/dL?

Treatment for Anemia in a 76-Year-Old Woman with Hemoglobin 10.5 g/dL

The first priority is to identify and treat the underlying cause of anemia before initiating any erythropoiesis-stimulating agents or transfusion therapy. 1

Immediate Diagnostic Workup Required

Before proceeding with treatment, the following must be evaluated:

• Complete iron studies: serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity to identify iron deficiency (the most common correctable cause in elderly patients) 1, 2
• Vitamin B12 and folate levels: nutritional deficiencies account for approximately one-third of anemia cases in elderly patients 2, 3
• Serum creatinine and estimated GFR: to assess for chronic kidney disease, which accounts for another third of cases in this population 4, 3
• Inflammatory markers (CRP, ESR): chronic inflammatory conditions are responsible for a significant proportion of anemia in elderly patients 2, 3
• Peripheral blood smear review: to evaluate red cell morphology and identify hemolysis, myelodysplastic features, or other hematologic abnormalities 1, 5
• Occult blood loss assessment: stool guaiac testing and evaluation for gastrointestinal or genitourinary bleeding 1, 2
• Thyroid function tests: hypothyroidism can contribute to anemia in elderly women 5

Treatment Algorithm Based on Etiology

If Iron Deficiency is Identified (Ferritin <100 ng/mL or TSAT <20%)

• Oral iron supplementation (ferrous sulfate 325 mg daily) is first-line for mild anemia without active bleeding 1
• Intravenous iron therapy should be considered if oral iron is not tolerated, malabsorption is present, or rapid correction is needed 6
• Target ferritin >100 ng/mL and TSAT >20% before considering erythropoiesis-stimulating agents 4

If Vitamin B12 or Folate Deficiency is Present

• Vitamin B12 replacement: 1000 mcg intramuscularly or high-dose oral supplementation 2
• Folate supplementation: 1 mg daily orally 2

If Chronic Kidney Disease is Identified (GFR <60 mL/min/1.73 m²)

• Initiate erythropoiesis-stimulating agent (ESA) only when hemoglobin is <10 g/dL and iron stores are adequate (ferritin >100 ng/mL, TSAT >20%) 1, 7, 4
• Darbepoetin alfa starting dose: 0.45 mcg/kg subcutaneously once weekly, or 0.75 mcg/kg every 2 weeks for non-dialysis patients 7
• Target hemoglobin: maintain between 10-11 g/dL; do NOT target levels >11 g/dL due to increased cardiovascular risks and mortality 1, 7
• Monitor hemoglobin weekly until stable, then monthly 7

If Myelodysplastic Syndrome is Suspected (Unexplained Anemia with Cytopenias)

• Bone marrow aspiration and biopsy with cytogenetics is required for diagnosis 1
• For symptomatic anemia with serum erythropoietin ≤500 mU/mL: epoetin alfa or darbepoetin alfa with or without G-CSF 1
• For del(5q) MDS: lenalidomide is the preferred treatment (category 1 recommendation) 1
• For higher-risk MDS: azacitidine or decitabine are recommended 1

If Anemia Remains Unexplained After Full Workup

• Approximately one-third of elderly patients have "unexplained anemia" likely due to age-related bone marrow resistance to erythropoietin and chronic subclinical inflammation 2, 3
• Conservative management with observation and supportive care is appropriate for mild anemia (Hb 10-12 g/dL) that is asymptomatic 2, 8
• Consider hematology referral if hemoglobin continues to decline or falls below 10 g/dL 5, 8

Red Blood Cell Transfusion Indications

Transfusion is NOT indicated at hemoglobin 10.5 g/dL in a stable, asymptomatic patient. 1

Transfusion should be considered only if:

• Symptomatic anemia is present (fatigue with functional impairment, dyspnea, chest pain, orthostatic hypotension, tachycardia) 1
• Hemoglobin falls below 8 g/dL in asymptomatic patients 1
• Hemoglobin falls below 10 g/dL with significant cardiovascular comorbidities or active ischemia 1
• Active bleeding with hemodynamic instability is present 1

When transfusion is indicated, administer single units and reassess hemoglobin before giving additional units to avoid overtransfusion 1

Critical Caveats and Pitfalls

• Do not initiate ESA therapy without first ensuring adequate iron stores: this is the most common cause of ESA failure 7, 4
• Avoid targeting hemoglobin >11 g/dL with ESAs: multiple trials demonstrate increased mortality, cardiovascular events, and stroke risk at higher targets 1, 7
• ESAs carry thromboembolism risk: use with caution in patients with history of stroke, malignancy, or thrombotic events 1, 7
• Anemia in elderly patients is rarely physiologic: even mild anemia (Hb 10-12 g/dL) is associated with increased hospitalization, cognitive decline, frailty, and mortality, so investigation is warranted 2, 5, 3
• Serum creatinine may be falsely reassuring in elderly patients: always calculate GFR, as reduced muscle mass can mask significant renal insufficiency 4