How do you diagnose and manage anemia in adult patients?

Diagnosis and Management of Anemia in Adults

Diagnostic Thresholds

Diagnose anemia and initiate comprehensive workup when hemoglobin falls below 13.5 g/dL in adult males or below 12.0 g/dL in adult females. 1, 2, 3

• These thresholds represent approximately 80% of normal mean hemoglobin levels and identify patients most likely to have pathological processes requiring intervention 1, 2
• Do not adjust thresholds downward for age in males, even though mean hemoglobin decreases after age 60, because lower levels typically indicate concurrent pathological conditions 3
• In chronic kidney disease patients specifically, initiate workup at hemoglobin <12 g/dL in adult males and postmenopausal females, or <11 g/dL in premenopausal females 2

Initial Laboratory Evaluation

Order a complete blood count with red cell indices, reticulocyte count, serum ferritin, transferrin saturation, and comprehensive metabolic panel as the foundation of your workup. 2

Pattern-Based Diagnostic Algorithm

For microcytic anemia (MCV <80 fL):

• Serum ferritin is the single most useful test for iron deficiency, with levels <45 μg/L providing optimal sensitivity and specificity 1, 4
• Ferritin <15 μg/L indicates absent iron stores; <30 μg/L indicates low body iron stores 4
• Critical pitfall: In inflammatory states, ferritin up to 100 μg/L may still represent iron deficiency—add transferrin saturation <20% to confirm functional iron deficiency 2, 4
• If iron studies are normal, order hemoglobin electrophoresis to exclude thalassemia 2, 4
• A low MCV with RDW >14.0% suggests iron deficiency, while low MCV with RDW ≤14.0% suggests thalassemia minor 4

For normocytic anemia (MCV 80-100 fL):

• Check creatinine to assess for chronic kidney disease 1
• Measure CRP to identify inflammatory anemia 1
• Consider combined deficiency states—simultaneous iron and B12/folate deficiency can mask typical MCV changes and present as normocytic anemia 2

For macrocytic anemia (MCV >100 fL):

• Check TSH and free T4 for hypothyroidism 1
• Measure serum folate (<10 nmol/L indicates deficiency) and vitamin B12 (<150 pmol/L indicates deficiency) 1
• If B12 is borderline, measure methylmalonic acid (>271 nmol/L confirms B12 deficiency) 1

Reticulocyte Count Interpretation

• Low reticulocyte count indicates deficiencies preventing erythropoiesis or bone marrow disease 2
• Elevated reticulocyte count (>100 × 10⁹/L) indicates hemolysis or acute blood loss—proceed with hemolysis workup 1, 2

Gastrointestinal Investigation Protocol

Perform urgent bidirectional endoscopy (gastroscopy and colonoscopy) as first-line investigations in all men and postmenopausal women with newly diagnosed iron deficiency anemia without obvious explanation. 1, 2

• Approximately one-third of men and postmenopausal women with iron deficiency anemia have underlying GI pathology, most commonly malignancy 1, 2
• This is an accepted indication for fast-track secondary care referral in the UK because GI malignancies can present with iron deficiency anemia, often without specific symptoms 1
• For patients unsuitable for colonoscopy, CT colonography is a reasonable alternative 1
• Screen all patients for celiac disease serologically or on small bowel biopsy at gastroscopy, as it is found in 3-5% of iron deficiency anemia cases 1, 2
• Perform urinalysis or urine microscopy to exclude urinary blood loss 1
• In recurrent or refractory iron deficiency anemia with negative bidirectional endoscopy, wireless capsule endoscopy is essential for small bowel assessment 1

Chronic Kidney Disease-Specific Management

Screen all CKD patients for anemia during initial evaluation, with hemoglobin testing at least annually regardless of CKD stage or cause. 1, 2, 3

• Anemia develops early in CKD and worsens with progressive renal insufficiency; prevalence increases from 8.7% in stage 2 to 52.4% in stage 5 2
• More frequent monitoring is indicated for patients with diabetes, greater disease burden, unstable clinical course, or evidence of previous hemoglobin decline 3
• In critical care patients with CKD, the guideline panel recommends treatment of anemic patients with erythropoietin, especially after trauma, in the absence of contraindications 1

Medication Review

Review all medications that may contribute to anemia or GI blood loss before considering advanced therapies. 2

• Specifically evaluate azathioprine and other immunosuppressants causing bone marrow suppression 2
• Consider NSAIDs, anticoagulants, and antiplatelet agents contributing to GI blood loss 5

Treatment Confirmation and Monitoring

A good response to iron therapy—defined as hemoglobin rise ≥10 g/L within a 2-week timeframe—confirms iron deficiency, even if initial iron studies were equivocal. 1, 2, 4

• Check hemoglobin response at 4 weeks after starting iron replacement 2
• Continue iron for 3 months after hemoglobin normalizes to replenish stores 2, 4
• Monitor hemoglobin and red cell indices at three-monthly intervals for one year, then after a further year 4
• Provide additional oral iron if hemoglobin or MCV falls below normal 4

Critical Pitfalls to Avoid

Never accept normal ferritin at face value in inflammatory states—ferritin >100 μg/L with transferrin saturation <20% still indicates functional iron deficiency. 2

Never assume negative endoscopy rules out GI blood loss—persistent or recurrent anemia requires capsule endoscopy for small bowel evaluation. 2

• The coexistence of iron deficiency anemia and hypercalcemia strongly suggests GI malignancy until proven otherwise 2
• Do not overlook combined deficiency states—simultaneous iron and B12/folate deficiency can mask typical MCV changes 2
• In critical care settings, implement phlebotomy reduction strategies to prevent iatrogenic anemia 1