Makindo Medical Notes

Related Subjects: | Sideroblastic Anaemia | Splenectomy

📘 About

• Sideroblastic anaemia is a rare form of anaemia characterised by ineffective erythropoiesis and the presence of ring sideroblasts in the bone marrow.
• Sideroblasts are erythroblasts (immature RBCs) with iron-loaded mitochondria encircling the nucleus (seen with Prussian Blue stain).
• Iron is available but cannot be incorporated into haem → leading to anaemia + systemic iron overload.

⚙️ Pathophysiology / Aetiology

• Final step in haem synthesis (ferrochelatase inserts Fe²⁺ into protoporphyrin IX) is impaired.
• Alcohol: interferes with pyridoxal-5’-phosphate (B6), a cofactor for ALAS (aminolevulinic acid synthase).
• Lead: inhibits ferrochelatase and ALA dehydratase.
• Hereditary forms: ALAS2 mutation (X-linked), ferrochelatase deficiency.
• Iron overload results from ineffective erythropoiesis, sometimes leading to hepatosplenomegaly.

🩺 Clinical Presentation

• Fatigue, weakness, pallor.
• Flow murmurs (high-output state due to anaemia).
• Hepatosplenomegaly from iron deposition.
• History: alcohol, drugs (isoniazid, pyrazinamide), family history.

🧪 Causes of Sideroblastic Anaemia

Cause	Mechanism	Examples
Acquired – Toxins	Disrupt haem synthesis	Alcohol, Lead
Acquired – Drugs	Block B6 metabolism	Isoniazid, Pyrazinamide
Myelodysplastic syndromes (MDS)	Ineffective erythropoiesis	Refractory anaemia with ring sideroblasts (RARS)
Hereditary	Genetic enzyme defects	ALAS2 mutation, ferrochelatase deficiency

🔎 Investigations

• Blood film: dimorphic picture (mix of microcytic & normocytic cells).
• Hypochromic microcytic anaemia common.
• Bone marrow biopsy: ring sideroblasts with perinuclear iron granules (Prussian Blue).
• Iron studies: ↑ serum iron, ↑ ferritin, ↑ transferrin saturation.
• Consider LFTs and genetic testing if hereditary suspected.

⚕️ Management

• Address underlying cause: stop alcohol, remove toxins/drugs.
• Pyridoxine (B6) trial: particularly in hereditary/ALAS2-related cases.
• Supportive: blood transfusions (but ↑ iron overload risk).
• Iron overload: consider iron chelation (e.g., deferoxamine).
• In severe/refractory cases: erythropoietin (EPO) or haematopoietic stem cell transplantation.

📚 References

• BNF – Anaemia management
• NICE CKS – Anaemia (non-iron deficiency)
• Hoffbrand’s Essential Haematology

Cases — Sideroblastic Anaemia

• Case 1 — Congenital form 👶: A 4-year-old boy is investigated for pallor and lethargy. Bloods: microcytic anaemia (Hb 8.5 g/dL, MCV 65 fL), high ferritin, high serum iron. Bone marrow: ring sideroblasts on Prussian blue staining. Family history: X-linked disorder. Diagnosis: congenital sideroblastic anaemia. Managed with pyridoxine supplementation and transfusion support.
• Case 2 — Acquired secondary (alcohol/toxin) 🍺: A 52-year-old man with chronic alcohol misuse presents with fatigue and breathlessness. Bloods: microcytic, hypochromic anaemia with raised serum iron. Bone marrow aspirate: ring sideroblasts. Diagnosis: acquired sideroblastic anaemia secondary to alcohol. Managed with alcohol cessation, pyridoxine, and supportive care.
• Case 3 — Myelodysplastic syndrome (clonal) 🧬: A 68-year-old woman presents with progressive anaemia and easy bruising. Bloods: Hb 9.0 g/dL, macrocytic indices, raised ferritin. Bone marrow: dysplastic changes with ring sideroblasts. Diagnosis: sideroblastic anaemia associated with MDS (RARS subtype). Managed with transfusions, iron chelation, and consideration of disease-modifying therapy (lenalidomide, azacitidine).

Teaching Point 🩺: Sideroblastic anaemia is characterised by defective haem synthesis → iron trapped in mitochondria around erythroblast nuclei (ring sideroblasts). Causes: congenital (X-linked), acquired (alcohol, lead, drugs, B6 deficiency), clonal (MDS). Iron studies: ↑ ferritin, ↑ serum iron, normal/↑ transferrin saturation. Management is cause-specific (e.g. pyridoxine, toxin removal, MDS therapy).