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

Abstract

The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload 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), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*<20 ms, in patients with thalassemia, SCA, or MDS. Patient inclusion criteria were an accurate record of erythrocyte concentrates (ECs) received, a transfusion history >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 iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (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 iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

Autoimmune cytopenias following allogeneic hematopoietic stem cell transplant in pediatric patients: Response to therapy and late effects

“…Short-and long-term effects of the most frequently used AIC treatments (steroids and rituximab) and supportive care measures (transfusions) are well established in various populations. 12,[34][35][36][37] Comparing our AIC cohort to controls, we found that iron overload and steroid-induced late effects including AVN and cataracts were more prevalent. This is likely attributed to the higher need of transfusion support leading to iron overload and prolonged courses of steroids to treat these AICs.…”

American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support

“…A second study also showed that among 41 chronically transfused patients with SCD with a mean age of 22.9 years, none developed a cardiac T2* of less than 20 ms during 2 years of follow-up. 159 In the third study, 6 of 201 patients developed cardiac iron overload; these 6 patients had poor chelation compliance, serum ferritin levels of more than 4600 ng/mL, and elevated liver iron concentrations of more than 22 mg/g (dw). 160 No studies reported iron-induced endocrinopathies or mortality with regard to MRI monitoring of iron overload.…”

“…Three observational studies showed an extremely low prevalence of cardiac T2* abnormalities in transfused patients with SCD, and evidence of cardiac iron loading developed only with prolonged elevated liver iron concentration. [158][159][160] One study of 9 chronically transfused pediatric patients with SCD showed no abnormal cardiac T2* 158 ; 4 had ventricular dilatation. A second study also showed that among 41 chronically transfused patients with SCD with a mean age of 22.9 years, none developed a cardiac T2* of less than 20 ms during 2 years of follow-up.…”

The effect of iron chelation therapy on overall survival in sickle cell disease and β‐thalassemia: A systematic review

“…Breakdown of mature red blood cells over time, in the absence of erythropoiesis, results in an accumulation of non‐transferrin‐bound iron (NTBI) once the transferrin‐binding capacity has been exceeded . In turn, the presence of NTBI results in iron deposits in the cells of various organs (including liver, heart, pancreas, endocrine glands, and joints) and the formation of reactive oxygen species . Ultimately, this can lead to symptoms associated with damage to involved organs, such as liver cirrhosis and hepatocellular carcinoma, diabetes mellitus, arthritis, arrhythmias, heart failure, and hypogonadotropic hypogonadism …”