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

Approach to Anemia in Adults

Begin with a complete blood count and MCV to classify anemia as microcytic, normocytic, or macrocytic, then follow a structured diagnostic pathway based on this classification, with serum ferritin being the single most powerful initial test for suspected iron deficiency. 1

Initial Laboratory Workup

Order these tests immediately:

• Complete blood count with MCV to categorize anemia type 1
• Reticulocyte count to distinguish regenerative (blood loss, hemolysis) from non-regenerative (production defect) anemia 1
• Serum ferritin as the most powerful single test for iron deficiency; <15 µg/L confirms absolute iron deficiency 1
• Consider transferrin saturation and additional iron studies only when ferritin is equivocal (15-100 µg/L) or inflammation is suspected 1

Classification-Based Diagnostic Algorithm

Microcytic Anemia (MCV <80 fL)

Iron deficiency is the most common cause 1, 2:

Critical action for men and postmenopausal women: Gastrointestinal investigation is mandatory, as 60-70% have an identifiable GI source and approximately one-third have underlying pathology including malignancy 1, 3

Specific workup steps:

• Bidirectional endoscopy (both upper and lower) as first-line investigation to exclude GI malignancy 1
• Obtain small bowel biopsies during gastroscopy even without celiac symptoms, as 2-5% of iron deficiency cases are due to celiac disease 1
• Screen with tissue transglutaminase antibody testing for celiac disease 1

Common pitfall: Never assume dietary deficiency alone in men and postmenopausal women—always investigate for GI pathology including malignancy 1, 3

Normocytic Anemia (MCV 80-100 fL)

This has the broadest differential 2, 4:

• Check serum ferritin first, as iron deficiency can present with normocytic anemia before becoming microcytic 1, 4
• Measure creatinine to assess for chronic kidney disease 1
• Check C-reactive protein to identify inflammatory causes 1
• Consider evaluation for chronic disease, malignancy (solid tumors or hematologic), rheumatologic disorders, and endocrine disorders 2, 4

Macrocytic Anemia (MCV >100 fL)

Follow this sequence:

• Measure vitamin B12 and folate levels as nutritional deficiencies are common and treatable 1, 2
• Check TSH and free T4 for hypothyroidism 1
• Consider alcohol use history, medication review (hydroxyurea, antiretrovirals), and evaluation for myelodysplastic syndromes or myeloma in older adults 2, 4

Essential History Elements

Focus on these specific details 1:

• Dietary intake patterns (vegetarian/vegan diet, pica)
• Medication use (NSAIDs, anticoagulants, PPIs, chemotherapy agents)
• GI symptoms (melena, hematochezia, dysphagia, early satiety, change in bowel habits)
• Previous GI or bariatric surgery (but do not let this preclude investigation for other causes) 1
• Family history of hematologic disorders (thalassemia, sickle cell disease)
• Menstrual history in premenopausal women

Management Principles

Iron Deficiency Anemia Treatment

Initiate ferrous sulfate 325 mg daily for 3-6 months to normalize hemoglobin and replenish stores 1:

• Expect hemoglobin rise of ≥10 g/L within 2 weeks if true iron deficiency, which confirms the diagnosis even with equivocal iron studies 1
• Lower-dose formulations may be as effective with fewer adverse effects 4
• Normalization of hemoglobin typically occurs by 8 weeks in most patients 4

Reserve intravenous iron for specific situations 1, 4:

• Patients intolerant of oral therapy
• Malabsorption syndromes
• Inflammatory bowel disease
• Chronic kidney disease

Common pitfall: Avoid over-supplementation, which can cause iron overload especially in hereditary hemochromatosis 1

Vitamin B12 Deficiency

Oral vitamin B12 is underused and can be as effective as intramuscular vitamin B12 in managing deficiency anemia 2

When to Consider Transfusion

Symptomatic patients with hemoglobin ≤8 g/dL may require blood transfusion 4, 5

Non-Responsive Patients

If patients do not benefit from appropriate therapy, evaluate for 2, 3:

• Non-adherence to prescribed regimen
• Malabsorption (celiac disease, inflammatory bowel disease, H. pylori gastritis)
• Ongoing occult bleeding
• Underlying systemic disease (chronic kidney disease, malignancy, chronic inflammation)
• Less common inherited disorders (thalassemia, sideroblastic anemia)

Special Population Considerations

Inflammatory bowel disease patients: Ferritin up to 100 µg/L may still reflect iron deficiency due to inflammation; consider intravenous iron for moderate-to-severe anemia or oral intolerance 1

Older adults: Anemia is associated with increased morbidity and mortality; in many cases the etiology remains unknown despite thorough evaluation, but this should not prevent investigation for treatable causes 4