What causes microcytic sideroblastic anemia in lead poisoning and how is it managed?

From the Guidelines

Lead poisoning causes microcytic sideroblastic anemia by inhibiting enzymes in the heme biosynthesis pathway, and management focuses on chelation therapy to remove lead from the body. The inhibition of enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and ferrochelatase prevents proper iron incorporation into protoporphyrin IX, resulting in iron accumulation in mitochondria of erythroid precursors and impaired hemoglobin synthesis.

Key Points in Management

• Chelation therapy is the primary treatment for lead-induced sideroblastic anemia
• For adults with blood lead levels above 70 μg/dL or with severe symptoms, intravenous calcium disodium EDTA (1000 mg/m²/day divided every 12 hours for 5 days) is recommended, often combined with dimercaprol (BAL) at 4 mg/kg IM every 4 hours for severe cases 1
• Supportive care includes removing the patient from the lead source, maintaining hydration, monitoring renal function, and possibly administering iron supplements after chelation begins
• Blood transfusions may be necessary for severe anemia, and monitoring of iron status and possible complications of iron overload is recommended, with iron loading treated with chelation therapy 1

Treatment Considerations

• The choice of chelation therapy depends on the severity of lead poisoning and the patient's overall health
• Oral succimer (DMSA) at 10 mg/kg every 8 hours for 5 days, then every 12 hours for 14 days is effective for less severe cases (blood lead levels 45-70 μg/dL)
• Follow-up monitoring of blood lead levels and complete blood counts is essential to assess treatment efficacy and prevent recurrence

From the Research

Causes of Microcytic Sideroblastic Anemia in Lead Poisoning

• Microcytic anemia in lead poisoning may be caused by coexisting iron deficiency, as suggested by a study published in 1988 2.
• The study found that children with lead poisoning and iron deficiency had lower mean corpuscular volume (MCV) and hemoglobin levels compared to those with normal iron levels.
• Another study published in 1990 3 also found that microcytosis in children with lead poisoning was due to coexistent iron deficiency or thalassemia trait.

Pathophysiology of Sideroblastic Anemia

• Sideroblastic anemia is characterized by the accumulation of ring sideroblasts in the bone marrow due to disrupted heme biosynthesis 4.
• The condition can be inherited or acquired, with acquired cases often being a result of myelodysplastic syndromes (MDS) or other reversible causes.
• A study published in 2015 5 found that X-linked sideroblastic anemia (XLSA) is caused by germline mutations in ALAS2, leading to defective heme synthesis and ineffective erythropoiesis.

Effects of Lead Poisoning on Red Blood Cells

• Lead poisoning can cause changes in red blood cell morphology and function, including increased resistance to hypotonic salt solution and shortened cell lifespan 6.
• The effects of lead on red blood cells can be neutralized by serum, which reacts with lead and eliminates its effects.

Management of Microcytic Sideroblastic Anemia

• The management of microcytic sideroblastic anemia depends on the underlying etiology, but may include vitamin B6 supplementation, red blood cell transfusions, and iron chelation therapy 4.
• In cases of acquired sideroblastic anemia due to MDS, the recently approved erythroid maturation agent Luspatercept may be used to manage anemia.