What is the next step in managing a 68-year-old female patient with elevated ferritin (Ferritin) levels, microcytic anemia (low Mean Corpuscular Volume (MCV)), and normal iron, B12, Gamma-Glutamyl Transferase (GGT), and Creatine Kinase (CK) levels?

Microcytic Anemia with Markedly Elevated Ferritin: Next Steps

This patient requires bone marrow examination with iron staining to evaluate for sideroblastic anemia or myelodysplastic syndrome, as the combination of microcytic anemia (MCV 69.7) with markedly elevated ferritin (1509 μg/L) and normal serum iron indicates a defect in iron utilization rather than iron deficiency or simple anemia of chronic disease. 1

Understanding This Laboratory Pattern

Your patient presents with a paradoxical picture that requires careful interpretation:

• Microcytic anemia (MCV 69.7, MCH 21.8, Hgb 11.5) with very high ferritin (1509 μg/L) is NOT typical iron deficiency anemia 2, 3
• The elevated hs-CRP (2.84) indicates some inflammation, but ferritin >1000 μg/L far exceeds what inflammation alone would cause in anemia of chronic disease 4, 5
• Normal serum iron with high ferritin suggests iron is being stored but not properly utilized for hemoglobin synthesis 1, 6

Why This Is NOT Simple Iron Deficiency

• Iron deficiency is definitively ruled out because ferritin >100 μg/L excludes iron deficiency even in the presence of inflammation 4, 3
• In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency, but 1509 μg/L is far beyond this threshold 4
• Microcytic anemia with normal iron studies and very high ferritin points to a disorder of iron utilization, not availability 1, 6

Why This Is NOT Simple Anemia of Chronic Disease

While the elevated hs-CRP suggests inflammation:

• Anemia of chronic disease typically presents with normocytic (not microcytic) anemia 7
• Ferritin levels >1000 μg/L are uncommon in simple anemia of chronic disease and warrant investigation for other causes 5
• In a study of 627 patients with ferritin >1000 μg/L, only 7 had simple anemia of chronic inflammation, while malignancy (153 cases) and iron-overload syndromes (136 cases) were far more common 5

Immediate Diagnostic Workup Required

Bone marrow examination is mandatory:

• Bone marrow aspirate and biopsy with Prussian blue iron staining to identify ring sideroblasts and evaluate for myelodysplastic syndrome 1
• This is the only way to definitively diagnose sideroblastic anemia, which presents exactly with this laboratory pattern 1
• MDS with ring sideroblasts can present identically to hereditary sideroblastic anemia, especially in older adults (your patient is 68) 1

Additional blood tests to order now:

• Serum copper and ceruloplasmin to evaluate for aceruloplasminemia, which presents with anemia, iron loading, and neurological symptoms 1
• Lactate dehydrogenase (LDH) and haptoglobin to definitively exclude hemolysis, though the microcytic picture makes this unlikely 1
• Peripheral blood smear review for dysplastic features, basophilic stippling, or ring sideroblasts (though bone marrow is definitive) 4, 1

Critical Management Points While Awaiting Diagnosis

Do NOT give iron supplementation:

• Iron supplementation can worsen toxicity in patients with iron overload 1
• This patient already has evidence of iron loading (ferritin 1509) and adding more iron could cause hepatic or cardiac toxicity 1

Monitor for iron overload complications:

• Check liver function tests and consider liver imaging (MRI) to assess for hepatic iron deposition 1
• Ferritin >1000 μg/L indicates significant iron burden that may already be causing organ damage 5

Differential Diagnosis to Consider

Most likely diagnoses in order of probability:

1. Myelodysplastic syndrome with ring sideroblasts - most common in this age group with this presentation 1
2. Acquired sideroblastic anemia - medication-induced (review all medications) or toxin exposure 1
3. Hereditary sideroblastic anemia - less likely at age 68 without prior diagnosis, but possible 4, 1
4. Occult malignancy - ferritin >1000 μg/L was most commonly associated with malignancy in one large series 5

Less likely but must exclude:

• Aceruloplasminemia (check copper/ceruloplasmin) 1
• Lead toxicity (occupational history?) 6
• Thalassemia trait (but would expect lifelong history) 2, 3

Common Pitfalls to Avoid

• Do not assume this is iron deficiency based solely on microcytosis - the very high ferritin excludes this 4, 3
• Do not attribute the high ferritin entirely to inflammation - hs-CRP of 2.84 is only mildly elevated and does not explain ferritin >1500 5
• Do not delay bone marrow examination - this is the definitive diagnostic test and cannot be replaced by peripheral blood tests alone 1
• Do not start empiric iron therapy - this could worsen iron overload and obscure the diagnosis 1