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Increased GI Absorption

NTDT patients can develop chronic iron overload even without regular blood transfusions

NTDT Overview_Increased GI Absorption

NTDT, non-transfusion-dependent thalassemia; LIC, liver iron concentration.

Ineffective erythropoiesis, chronic anemia, hypoxia

  • The combination of ineffective erythropoiesis, anemia, and hypoxia leads to a compensatory increase in serum levels of erythropoietin (EPO) as well as a decrease in serum levels of hepcidin, which controls the concentration of ferroportin on the intestinal epithelium.

Hepcidin suppression

  • Two proposed regulators of hepcidin production are growth differentiation factor 15 (GDF-15), secreted by erythroid precursors, and hypoxia inducible transcription factors (HIFs).
  • The pathophysiology of iron loading in NTDT appears similar to that observed in patients with hereditary forms of hemochromatosis, which are characterized by impaired hepcidin production.

Duodenal iron absorption

  • Regardless of the signaling mechanism, the end result is suppression of hepcidin levels, increased intestinal iron absorption, and increased release of recycled iron from the reticuloendothelial system, which leads to depletion of macrophage iron, relatively low levels of serum ferritin, and preferential portal and hepatocyte iron loading, resulting in increased LIC.