What is the diagnosis and management for a patient with erythrocytosis, microcytosis, hypochromia, and anisocytosis?

Microcytic Hypochromic Anemia with Elevated RDW

Most Likely Diagnosis

This presentation is most consistent with iron deficiency anemia (IDA), which requires immediate investigation for the underlying cause of iron loss, particularly gastrointestinal blood loss in adults. 1

The combination of low MCV, low MCH, low MCHC with high RDW (>14.0%) is the classic pattern that distinguishes iron deficiency from thalassemia trait, where RDW would typically be normal or only mildly elevated (≤14.0%). 1, 2 The elevated RBC count you mention is somewhat atypical for IDA but can occur in early or mild cases.

Diagnostic Confirmation

Serum ferritin is the single most powerful test for confirming iron deficiency, with the following interpretation: 1, 2

• <15 μg/L: Diagnostic of absent iron stores 2
• <30 μg/L: Indicates low body iron stores 2
• <45 μg/L: Optimal cut-off for clinical practice (best sensitivity/specificity) 1, 2
• >150 μg/L: Makes iron deficiency unlikely 1

Critical caveat: Ferritin is an acute phase reactant and can be falsely elevated in inflammation, malignancy, or liver disease. 3 If ferritin is 12-100 μg/L with suspected inflammation, add transferrin saturation (TSAT <30% supports iron deficiency). 3, 1

Investigation for Underlying Cause

In adult men and post-menopausal women, gastrointestinal blood loss is the most common cause and requires investigation. 3, 2 Fast-track GI referral is warranted for: 1

• Men with Hb <110 g/L
• Non-menstruating women with Hb <100 g/L
• Any confirmed iron deficiency with concerning symptoms

Key causes to investigate systematically: 3

• GI blood loss: NSAID use, colon cancer/polyps, gastric cancer, angiodysplasia, inflammatory bowel disease
• Malabsorption: Celiac disease (screen if suspected), prior gastric surgery, bacterial overgrowth
• Dietary insufficiency: Particularly in adolescents or restrictive diets
• Menstrual blood loss: In pre-menopausal women

Treatment Algorithm

First-line treatment is oral ferrous sulfate 200 mg three times daily for at least 3 months after hemoglobin correction to replenish iron stores. 1, 2

Expected response confirming diagnosis: Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks. 1, 2 This therapeutic response itself confirms iron deficiency.

Alternative oral formulations if ferrous sulfate not tolerated: 1, 2

• Ferrous gluconate
• Ferrous fumarate
• Add ascorbic acid (vitamin C) to enhance absorption 2

If no response to oral iron after 2-4 weeks, consider: 1, 2

• Malabsorption: Switch to intravenous iron (expect Hb increase ≥2 g/dL within 4 weeks) 1
• Ongoing blood loss: Intensify investigation
• Non-compliance: Address barriers
• Wrong diagnosis: Consider genetic disorders (see below)

Monitoring

Follow hemoglobin and red cell indices at 3-month intervals for one year, then again at 2 years. 2 Provide additional oral iron if hemoglobin or MCV falls below normal. 2

Alternative Diagnoses to Consider

If iron studies are normal or patient fails to respond to iron therapy, consider: 1, 2

Thalassemia Trait

• Pattern: Low MCV with RDW ≤14.0% (not >14.0% as in your case) 1, 2
• Key feature: Elevated RBC count disproportionate to degree of anemia 4
• Diagnosis: Hemoglobin electrophoresis if appropriate ethnic background or MCV disproportionately low relative to anemia 1

Genetic Iron Metabolism Disorders (Rare)

Only consider if refractory to standard iron therapy with confirmed low iron stores: 3, 1

• SLC11A2 defects: Microcytic anemia with increased TSAT and variable ferritin 3, 2
• TMPRSS6 defects (IRIDA): Resistant to oral iron, requires repeated IV iron 1
• SLC25A38 defects: Severe transfusion-dependent sideroblastic anemia with ring sideroblasts 3

Anemia of Chronic Disease

• Can present with microcytosis but typically has elevated or normal ferritin (>100 μg/L) with low TSAT 3

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency without confirming with ferritin. 1 Thalassemia and anemia of chronic disease require different management.
• Do not overlook combined deficiencies (iron with B12 or folate), which may be recognized by elevated RDW despite microcytosis. 3, 2
• Do not stop investigating after starting iron therapy. The underlying cause of iron loss must be identified, especially to exclude malignancy. 3, 1
• Do not use hemoglobin level alone to decide on investigation. Even mild anemia with confirmed iron deficiency warrants investigation for the source. 1