What is the approach to diagnosing and managing anemia in an adult patient without a specified medical history?

Diagnostic Approach to Anemia in Adults

Begin by confirming anemia with hemoglobin <130 g/L in men or <120 g/L in non-pregnant women, then classify by mean corpuscular volume (MCV) to guide your diagnostic workup and identify the underlying cause before initiating treatment. 1, 2

Initial Laboratory Assessment

• Obtain a complete blood count with MCV to classify anemia as microcytic (MCV <80 fL), normocytic (MCV 80-100 fL), or macrocytic (MCV >100 fL) 1, 3
• Check reticulocyte count to distinguish regenerative (>10×10⁹/L) from non-regenerative anemia 1
• Measure serum ferritin as the single most powerful test for iron deficiency; <15 µg/L confirms absolute iron deficiency 1, 2
• Consider transferrin saturation (<20%) and other iron studies when ferritin is equivocal or inflammation is suspected (ferritin may be falsely elevated up to 100 µg/L with concurrent inflammation) 1, 2

Classification-Based Diagnostic Pathway

Microcytic Anemia (MCV <80 fL)

• Iron deficiency anemia is the most common cause 3, 4
• Obtain iron profile: ferritin, transferrin saturation, serum iron 1
• In men and postmenopausal women with confirmed iron deficiency, gastrointestinal investigation is mandatory as 60-70% have an identifiable GI source and approximately one-third have underlying pathology including malignancy 1, 3
• Screen for celiac disease with tissue transglutaminase antibody testing, as 3-5% of IDA cases are due to celiac disease 1, 2
• Perform urinalysis to exclude urinary blood loss 1

Normocytic Anemia (MCV 80-100 fL)

• Check creatinine to assess for chronic kidney disease 1
• Measure C-reactive protein to identify inflammatory causes 1
• Consider vitamin B12 and folate deficiency (can present before MCV elevation) 1, 3
• Evaluate for chronic disease, malignancy, endocrine disorders, and rheumatologic conditions 3, 5

Macrocytic Anemia (MCV >100 fL)

• Check TSH and free T4 for hypothyroidism 1
• Measure vitamin B12 (<150 pmol/L indicates deficiency) and folate levels 1, 3
• If B12 level is borderline, measure methylmalonic acid (>271 nmol/L confirms B12 deficiency) 1
• Consider myelodysplastic syndrome, particularly in older adults 3, 5
• Review medications (hydroxyurea, antiretrovirals) and assess alcohol use 3

Critical History and Physical Examination Elements

Take a detailed history focusing on:

• Dietary intake (though borderline deficiency alone should not preclude full investigation in at-risk populations) 1
• Medication use, particularly NSAIDs, aspirin, and anticoagulants 1
• GI symptoms (though these rarely correlate with investigation findings) 1
• Menstrual history in premenopausal women 4
• Previous GI or bariatric surgery (though this should not preclude investigation for other causes) 1
• Family history of hematologic disorders, telangiectasia, or bleeding disorders 1

Gastrointestinal Investigation Protocol for Iron Deficiency

For men and postmenopausal women with unexplained IDA, perform bidirectional endoscopy (gastroscopy and colonoscopy) as first-line investigation to exclude GI malignancy 1, 2

• Obtain small bowel biopsies during gastroscopy even without symptoms, as celiac disease is found in 2-3% of IDA cases 1
• Complete lower GI tract examination is mandatory unless upper endoscopy reveals carcinoma or celiac disease, as dual pathology occurs in 10-15% of patients 1
• Do not accept oesophagitis, erosions, or peptic ulcer as the sole cause without completing lower GI investigation 1
• CT colonography is a reasonable alternative when colonoscopy is not feasible 1

Management Principles

Initiate iron replacement therapy with ferrous sulfate 325 mg (65 mg elemental iron) daily for 3-6 months to normalize hemoglobin and replenish stores 2

• Expect hemoglobin rise of ≥10 g/L within 2 weeks if true iron deficiency; this response confirms the diagnosis even with equivocal iron studies 1
• Lower-dose formulations may be equally effective with fewer adverse effects 5
• Reserve intravenous iron for patients intolerant of oral therapy, malabsorption, or specific conditions like inflammatory bowel disease or chronic kidney disease 1, 2
• Patients not responding to therapy require evaluation for non-adherence, malabsorption, ongoing blood loss, or systemic disease 3

Common Pitfalls to Avoid

• Never assume dietary deficiency alone in men and postmenopausal women—always investigate for GI pathology including malignancy 2
• Do not rely solely on transferrin saturation when ferritin is unavailable, as it has limited specificity 2
• Do not accept a history of GI surgery as the sole explanation without excluding other causes, particularly in those at risk for malignancy 1
• Avoid over-supplementation, which can cause iron overload especially in hereditary hemochromatosis 2
• Do not stop investigation based on NSAID use or anticoagulation—these should not deter full evaluation 1

Special Populations

In critical care patients, implement phlebotomy reduction strategies and restrictive transfusion thresholds 1

In inflammatory bowel disease, ferritin up to 100 µg/L may still reflect iron deficiency; consider intravenous iron for moderate-to-severe anemia (Hb <100 g/L) or oral intolerance 1

In older adults, anemia is associated with increased morbidity and mortality; unknown etiology is common but does not preclude thorough investigation 5