Pure red cell aplasia

Overview

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• Description: normocytic, normochromic anemia characterized by a severe reduction in circulating reticulocytes and marked reduction or absence of erythroid precursors in the bone marrow
• Pathophysiology: thought to be related to abnormal T-cell function and IgG antibodies that target erythroblasts and erythropoietin
  • Etiology
    • Acquired
      • Most often idiopathic
      • Possible associated conditions
        • Thymoma
        • Myelodysplastic syndrome
        • Adverse drugs effects (e.g., from phenytoin, chloramphenicol)
        • Parvovirus B19 infection
        • Autoimmune disorders (e.g., type 1 diabetes, thyroiditis, rheumatoid arthritis)
    • Congenital: Diamond-Blackfan anemia (DBA): see below
• Diagnostics
  • Low reticulocyte count
  • Bone marrow biopsy shows marked reduction or absence of erythroid precursors.
• Treatment
  • Treatment of the underlying cause (e.g., cessation of possible offending agents, thymectomy)
  • Red blood cell transfusion for symptomatic patients
  • Immunosuppressive and/or cytotoxic agents (e.g., glucocorticoids, cyclosporine, cyclophosphamide)

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Diamond-Blackfan anemia

• Pathophysiology: Congenital pure red cell aplasia (PRCA) due to ribosomal defect (e.g., RPS19 mutation) causing accelerated erythroid apoptosis; presents at age &lt 1 yr (peak 2–6 mos). c
• Clinical Presentation:
  • Severe Anemia: Pallor, lethargy, poor feeding, FTT, systolic flow murmur.
  • Congenital Anomalies (~50%): Triphalangeal/bifid thumbs, cleft lip/palate, micrognathia, hypertelorism, webbed neck, short stature.
• Diagnosis:
  • Initial (CBC): Severe macrocytic anemia (↑ MCV) with reticulocytopenia (<1%); normal WBC and platelet counts.
  • Key Biomarkers: ↑ Erythrocyte Adenosine Deaminase (eADA) (high-yield discriminator) and ↑ HbF.
  • Confirmatory (BM Biopsy): Isolated erythroid hypoplasia (normal myeloid & megakaryocyte lineages); confirmed by genetic panel.
• Key Differentials:
  • Fanconi Anemia: Presents later (age 4–8 yrs) with pancytopenia, absent/hypoplastic thumbs, café-au-lait spots; (+) chromosomal breakage test.
  • Transient Erythroblastopenia of Childhood (TEC): Acquired, age >1 yr, normocytic anemia, normal eADA, no physical anomalies, self-resolving.
• Management:
  • 1st-Line: Corticosteroids (oral prednisone).
  • 2nd-Line: Chronic PRBC transfusions + iron chelation (deferasirox) for non-responders or infants <1 yr.
  • Curative: Allogeneic HSCT (definitive for refractory/transfusion-dependent cases).
• Complications: Secondary hemochromatosis (iron overload), steroid toxicity (growth failure), and increased risk of MDS/AML and solid tumors.