In an adult male with severe microcytic, hypochromic anemia (hemoglobin 7.3 g/dL, MCV 66.7 fL, RDW 18.7 %), basophilic stippling, borderline low vitamin B12 and folate, normal white‑blood‑cell and platelet counts, and a total PSA of 3.7 ng/mL, what are the most likely causes and what immediate diagnostic and therapeutic actions should be taken?

Severe Microcytic Hypochromic Anemia with Basophilic Stippling: Immediate Management

This adult male requires immediate gastrointestinal investigation with upper endoscopy and colonoscopy to identify occult blood loss, while simultaneously starting oral iron supplementation and ordering serum ferritin and transferrin saturation to confirm iron deficiency. 1

Immediate Diagnostic Actions

First-Line Laboratory Tests

• Order serum ferritin, transferrin saturation (TSAT), and C-reactive protein (CRP) as the essential first-line tests to distinguish iron-deficiency anemia from other causes of microcytosis 1
• Ferritin <15 μg/L confirms absent iron stores with 99% specificity, while <30 μg/L indicates low body iron stores 1
• A ferritin cut-off of 45 μg/L provides optimal sensitivity and specificity for iron deficiency in routine practice 1
• TSAT <16-20% confirms iron deficiency, particularly when ferritin may be falsely elevated by inflammation 1

Key Diagnostic Clues from Current Labs

• The combination of extremely low MCV (66.7 fL) with markedly elevated RDW (18.7%) strongly favors iron deficiency over thalassemia, which typically presents with RDW ≤14.0% 1
• The presence of basophilic stippling, microcytosis, hypochromasia, and polychromasia on peripheral smear supports iron deficiency but also raises concern for lead toxicity or sideroblastic anemia 2
• Borderline low B12 (197 pg/mL) and borderline folate (4.5 ng/mL) suggest combined deficiencies, recognizable by the elevated RDW 1

Immediate Therapeutic Intervention

Start Oral Iron Supplementation Now

• Begin ferrous sulfate 200 mg three times daily immediately while diagnostic workup proceeds 1
• Do not delay iron therapy waiting for ferritin results, as severe anemia (hemoglobin 7.3 g/dL) requires urgent treatment 1
• Expect hemoglobin rise ≥10 g/L within 2 weeks if iron deficiency is the cause 1
• Continue iron for at least three months after correction of anemia to replenish iron stores 1
• If oral iron is not tolerated, consider ferrous gluconate or ferrous fumarate; adding ascorbic acid enhances absorption 1

Mandatory Investigation for Source of Blood Loss

Gastrointestinal Evaluation is Non-Negotiable

• Adult males with hemoglobin <110 g/L warrant fast-track gastrointestinal referral for both upper endoscopy and colonoscopy 1
• Do not attribute severe iron-deficiency anemia in adults solely to dietary insufficiency; occult gastrointestinal blood loss, especially from malignancy, must be excluded 1
• Upper endoscopy identifies an underlying cause in 30-50% of patients with iron-deficiency anemia 1

Specific Endoscopic Targets

• Upper endoscopy with small bowel biopsies to screen for celiac disease (present in 2-3% of iron-deficiency anemia cases), gastric cancer, NSAID-induced gastropathy, peptic ulcer disease, and angiodysplasia 1
• Colonoscopy to detect colonic carcinoma, adenomatous polyps, angiodysplasia, and inflammatory bowel disease 1

Differential Diagnosis Considerations

When to Suspect Genetic Disorders

• The extremely low MCV (66.7 fL) with severe anemia raises concern for genetic disorders of iron metabolism or heme synthesis, particularly if ferritin is normal/high or if the patient fails to respond to oral iron 1, 3
• Consider genetic testing for SLC11A2, STEAP3, SLC25A38, ALAS2, or ABCB7 defects if extreme microcytosis (MCV <70) persists despite adequate iron replacement 1, 3

Sideroblastic Anemia Warning Signs

• Basophilic stippling on peripheral smear is a key finding in sideroblastic anemia and lead toxicity 2
• If ferritin is normal or elevated with persistent microcytosis, bone marrow examination to look for ring sideroblasts is recommended 3, 4
• For X-linked sideroblastic anemia (ALAS2 defects), a trial of pyridoxine (vitamin B6) 50-200 mg daily initially is recommended, with maintenance at 10-100 mg daily if responsive 1, 3

Thalassemia Considerations

• Order hemoglobin electrophoresis if microcytosis persists with normal iron studies or if MCV is disproportionately low relative to the degree of anemia 1
• Elevated red blood cell count with microcytosis suggests thalassemia trait rather than iron deficiency 4

Address Combined Deficiencies

B12 and Folate Supplementation

• The borderline low B12 (197 pg/mL) and low folate (4.5 ng/mL) require supplementation, as iron deficiency can coexist with B12 or folate deficiency 1
• Start oral B12 supplementation and folic acid while investigating the cause of combined deficiencies 1
• Malabsorption disorders such as celiac disease, H. pylori infection, or autoimmune atrophic gastritis can cause both iron and B12/folate deficiency 1

Monitoring and Follow-Up

Expected Response to Iron Therapy

• Hemoglobin should rise ≥10 g/L within 2 weeks if iron deficiency is the cause 1
• If hemoglobin increases by at least 2 g/dL within 4 weeks, this confirms iron deficiency 1
• Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year 1

Failure to Respond to Oral Iron

• If the patient fails to respond to oral iron within 2-4 weeks, consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders 1
• Switch to intravenous iron (iron sucrose or iron gluconate) if malabsorption is confirmed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 1
• IRIDA (iron-refractory iron deficiency anemia) should be considered if there is remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron 1

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease (TSAT <20% with ferritin >100 μg/L), thalassemia, and sideroblastic anemia require different management 1
• Do not rely on ferritin alone when inflammation is present; CRP should be measured concurrently because ferritin is an acute-phase reactant that can be falsely elevated 1
• Do not delay gastrointestinal investigation even if dietary insufficiency or other causes seem explanatory, as occult malignancy must be excluded 1
• Do not overlook combined deficiencies—the elevated RDW signals possible coexisting B12 or folate deficiency 1
• Do not forget to replenish iron stores—continue iron for at least three months after anemia correction 1