Results from a study recently published in the British Journal of Haematology indicate a pathological cycle with hemolysis, inflammatory response, and iron overload (IO) in patients with congenital hemolytic anemias (CHAs).

CHAs are rare, inherited, heterogeneous diseases characterized by abnormal erythropoiesis, erythrocyte membranes, and erythrocyte metabolism. In this study, researchers assessed erythropoietin, hepcidin, nontransferrin bound iron (NTBI), serum levels of cytokines, cardiac and hepatic magnetic resonance imaging, and routine iron parameters to determine whether they were predictive of IO in patients with different CHAs.

Of the 52 patients assessed, 21 (40%) had a liver iron concentration (LIC) greater than 4 mg iron/g dry weight. IO of the liver was found to be associated with NTBI (P =.003), high levels of ferritin (P =.0025), and transferrin saturation (P =.002).

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The combination of ferritin levels greater than 500 μg/L with transferrin saturation greater than 60% was the best predictor of increased LIC. Of note, in cases with discordant values, changes in transferrin saturation were more important for predicting LIC.

According to this analysis, potentially confounding factors such as metabolic syndrome, hepatic disease, hereditary hemochromatosis-associated mutations, and transfusions had minimal effects on IO.

Levels of both erythropoietin and hepcidin were increased in patients with CHAs compared with patients without CHAs. Increased erythropoietin was associated with increased LIC (P <.001), and increased hepcidin was associated with increased ferritin (P <.05).

The cytokine gamma interferon (IFN-g) was increased in patients with CHAs. Levels of both interleukin 6 and IFN-g correlated with levels of ferritin and hepcidin.

“Overall, these findings suggest the existence of a vicious cycle between chronic hemolysis, inflammatory response, and IO in patients with CHAs,” concluded the authors.

Reference

1.     Barcellini W, Zaninoni A, Gregorini AI, et al. Iron overload in congenital haemolytic anaemias: role of hepcidin and cytokines and predictive value of ferritin and transferrin saturation [published online March 3, 2019]. Br J Haematol. doi:10.1111/bjh.15811