Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

The risk and clinical significance of cardiac ironoverload due to chronic transfusion varies with the underlying disease. Cardiac ironoverload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia(SCA), irondoes not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac ironoverload, defined as a cardiovascular magnetic resonance T2* 8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent ironoverload in patients with SCA. Cardiac ironoverload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver ironcontent (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound ironwas high in the thalassemiaand MDS groups but low in the SCA group (P<0.001). Hepcidinwas low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that irondeposition largely spares the heart in SCA: the high level of erythropoiesisrecycles the ironand the chronic inflammation retains ironwithin the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Ironaccumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess ironsupply, and inflammation.