What is the most likely diagnosis and appropriate work‑up and management for a patient with low hemoglobin, low mean corpuscular hemoglobin concentration, and elevated red‑cell distribution width?

Low Hemoglobin, Low MCHC, and Elevated RDW: Iron Deficiency Anemia

This presentation is most consistent with iron deficiency anemia (IDA), and you should immediately check serum ferritin as the most powerful diagnostic test, followed by comprehensive gastrointestinal evaluation to identify the source of blood loss or malabsorption. 1

Diagnostic Interpretation

The combination of low hemoglobin, low MCHC (hypochromia), and elevated RDW indicates:

• Microcytic, hypochromic anemia with increased red cell size variability 1, 2
• Elevated RDW (>15%) is characteristic of iron deficiency, distinguishing it from other microcytic anemias like thalassemia which typically have normal RDW 1, 2
• Low MCHC reflects inadequate hemoglobin concentration within red cells, a hallmark of iron-restricted erythropoiesis 3, 2

Critical Caveat

Combined deficiencies (e.g., iron plus folate/B12) may mask microcytosis but are revealed by elevated RDW, so don't dismiss iron deficiency if MCV appears normal 1

Initial Laboratory Work-Up

Minimum essential tests: 2

• Serum ferritin - most powerful test for iron deficiency; <12-15 μg/dL is diagnostic 1
• Transferrin saturation - <15-16% supports iron deficiency 3, 1
• Complete blood count with indices - confirm MCV, review peripheral smear 3
• Reticulocyte count - low/normal indicates inadequate bone marrow response 3, 2
• C-reactive protein (CRP) - to assess for inflammation that may elevate ferritin 2

Ferritin Interpretation Algorithm

Without inflammation (normal CRP): 2

• Ferritin <30 μg/L = iron deficiency
• Ferritin <12 μg/L = definitive iron deficiency 1

With inflammation (elevated CRP): 1, 2

• Ferritin <100 μg/L may still indicate iron deficiency
• Ferritin >100 μg/L essentially excludes iron deficiency 1
• Consider transferrin saturation <30% or soluble transferrin receptor for confirmation 1, 4

Gastrointestinal Evaluation - Critical for All Patients

In adult men and postmenopausal women, GI blood loss is the most common cause and asymptomatic GI malignancy must be excluded. 1

Mandatory investigations: 1

Upper GI endoscopy with small bowel biopsy:

• Excludes gastric cancer, peptic ulcer disease, angiodysplasia 1
• Small bowel biopsy screens for celiac disease (present in up to 4% of cases) 1, 5

Colonoscopy or CT colonography:

• Excludes colorectal cancer, polyps, inflammatory bowel disease 1
• Particularly critical in patients ≥50 years or with family history 5

Celiac serology (tissue transglutaminase antibody):

• Should be checked in all patients before endoscopy 5, 4

Premenopausal Women - Age-Stratified Approach

Age <50 years: 5

• Check celiac serology in all patients
• Upper GI endoscopy only if upper GI symptoms present
• Colonoscopy reserved for: lower GI symptoms, strong family history (≥2 first-degree relatives or 1 affected <50 years), or persistent IDA despite iron replacement and correction of menstrual losses

Age ≥50 years: 5

• Full GI evaluation (upper endoscopy and colonoscopy) as outlined above

Additional History Elements to Elicit

Dietary assessment: 1

• Iron-deficient diet (though positive history should not deter full GI investigation)

Medication review: 1

• NSAIDs and aspirin - major cause of occult GI blood loss; stop if possible
• Anticoagulants - note but don't defer investigation

Blood loss sources: 1

• Menstrual history in premenopausal women
• Blood donation frequency
• Visible blood in stool

Symptoms suggesting underlying pathology: 3

• Fatigue disproportionate to activity and not relieved by rest
• Syncope, dyspnea, chest pain, headache
• Jaundice, neurologic symptoms (suggest hemolysis or B12 deficiency)

Treatment Approach

First-line: Oral iron supplementation 5, 4, 6

• Ferrous sulfate, ferrous fumarate, or ferrous gluconate (least expensive, reasonable first choice) 4
• Best absorbed on empty stomach, but may take with food if not tolerated 4
• Adding vitamin C 500 mg improves absorption 5, 4
• Intermittent dosing (every other day) is as effective as daily with fewer side effects 6
• Continue until hemoglobin normalizes AND for 3 months after to replenish stores 5

Intravenous iron indications: 5, 4, 6

• Intolerance to oral iron (nausea, abdominal pain, constipation)
• Malabsorption (celiac disease, inflammatory bowel disease)
• No response to oral iron after 3 weeks
• Severe anemia requiring rapid repletion
• Modern formulations (iron sucrose, ferric carboxymaltose) have low anaphylaxis risk but resuscitation facilities must be available 5

Follow-Up Monitoring

After initiating treatment: 5

• Hemoglobin and red cell indices at 3-month intervals for 1 year
• Then annually, or if symptoms recur
• Further investigation only if hemoglobin/indices cannot be maintained with oral iron

Reassuring prognosis: Even when no GI source is identified after complete evaluation, long-term outlook is good and iron deficiency rarely recurs 5, 1