What is the appropriate workup and treatment for a 73-year-old patient with unexplained anemia?

Workup for Unexplained Anemia in a 73-Year-Old Patient

In a 73-year-old patient with unexplained anemia, immediately obtain a complete blood count with red cell indices, reticulocyte count, iron studies (ferritin, transferrin saturation, TIBC), serum creatinine with GFR calculation, and refer urgently to gastroenterology for bidirectional endoscopy to exclude gastrointestinal malignancy. 1, 2, 3

Initial Laboratory Assessment

Essential First-Line Tests

• Complete blood count with MCV to classify anemia as microcytic (MCV <80 fL), normocytic (MCV 80-100 fL), or macrocytic (MCV >100 fL) 2, 3

• Reticulocyte count to distinguish impaired red cell production from increased destruction or blood loss 2, 3

• Iron studies panel including serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity 2, 3

• Serum creatinine and calculated GFR since chronic kidney disease is a common cause of anemia in older adults 2, 3

• C-reactive protein (CRP) to identify anemia of chronic inflammation 3

Additional Testing Based on Initial Results

• Vitamin B12 and folate levels if MCV >100 fL or if macrocytosis is present 1, 3

• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism as a contributing factor 2

• Tissue transglutaminase antibody (tTG-IgA) with total IgA to screen for celiac disease, which causes approximately 5% of iron deficiency anemia cases 2, 4

• Urinalysis to detect occult hematuria as a source of blood loss 3

Interpretation of Iron Studies

Iron Deficiency Anemia

• Ferritin <30 μg/L confirms absolute iron deficiency without inflammation 2, 3

• TSAT <20% indicates inadequate iron availability for red cell production 2

• In the presence of inflammation, ferritin up to 100 μg/L may still represent iron deficiency; measure CRP to assess inflammatory state 3

Anemia of Chronic Disease/Inflammation

• Ferritin >100 μg/L with TSAT <20% suggests functional iron deficiency from chronic inflammation 2, 3

• This pattern requires treatment of the underlying inflammatory condition 3

Urgent Gastrointestinal Evaluation

Indications for Immediate Gastroenterology Referral

All men and postmenopausal women with unexplained iron deficiency anemia require urgent bidirectional endoscopy (gastroscopy and colonoscopy) to exclude gastrointestinal malignancy. 1, 2, 4

• Approximately one-third of men and postmenopausal women with iron deficiency anemia have underlying gastrointestinal pathology 1

• Upper gastrointestinal cancer occurs in 1/7 the frequency of colon cancer in this population 4

• Dual pathology (both upper and lower GI bleeding sources) occurs in 1-10% of patients, so both endoscopies are required 2

When Small Bowel Investigation Is Needed

• Capsule endoscopy, CT enterography, or MRI enterography should be performed if bidirectional endoscopy is negative but red flags are present 4

• Red flags include involuntary weight loss, persistent abdominal pain, elevated CRP, or refractory anemia despite treatment 4

Renal Function Assessment

Chronic Kidney Disease Evaluation

• If GFR <30 mL/min/1.73 m², refer to nephrology for evaluation of anemia of chronic kidney disease 2

• Patients with chronic kidney disease require hemoglobin monitoring every 3 months 3

• Complete anemia workup is required if hemoglobin <13 g/dL in men or <12 g/dL in women with chronic kidney disease 3

Hematology Referral Criteria

When to Involve a Hematologist

• Unexplained anemia after completing initial workup including negative bidirectional endoscopy and normal iron studies 2

• Suspected hemolysis based on elevated reticulocyte count (>100 × 10⁹/L) with negative bleeding source 2

• Macrocytic anemia with normal B12 and folate raising concern for myelodysplastic syndrome, particularly in patients over 70 years 3, 5

• Refractory anemia not responding to appropriate iron or vitamin replacement 1

Initial Management While Awaiting Workup

Iron Replacement Therapy

• Oral iron supplementation (100-200 mg elemental iron daily) is first-line treatment for confirmed iron deficiency anemia 2, 4

• Lower doses may be equally effective with fewer gastrointestinal side effects 6

• Treatment duration of 3-6 months is typically required to normalize hemoglobin and replenish iron stores 4

Intravenous Iron Indications

• IV iron is indicated for oral iron intolerance, malabsorption, chronic inflammatory conditions, or failure to respond to oral therapy 2, 4

• Ensure ferritin >100 μg/L and TSAT >20% before considering erythropoietin therapy if anemia persists 2

Common Pitfalls to Avoid

• Do not attribute anemia to "normal aging" in elderly patients—a comprehensive evaluation is always necessary 3, 6

• Do not delay gastroenterology referral while treating with iron supplementation, as this may mask gastrointestinal malignancy 2

• Do not treat with folic acid before excluding vitamin B12 deficiency, as this may precipitate subacute combined degeneration of the spinal cord 1

• Do not assume a single cause—older adults frequently have multifactorial anemia requiring evaluation for concurrent nutritional deficiencies 3, 5

• Do not overlook medication history, particularly NSAIDs, aspirin, and anticoagulants that may contribute to occult blood loss 2