Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease

Abstract

Transfusional iron overload represents a substantial challenge in the management of patients with sickle cell disease (SCD) who receive chronic or episodic red blood cell transfusions. Iron-induced cardiomyopathy is a leading cause of death in other chronically transfused populations but rarely seen in SCD. Study objectives were to: (i) examine the extent of myocardial and hepatic siderosis using magnetic resonance imaging (MRI) in chronically transfused SCD patients, and (ii) evaluate the relationship between long-term (over the 5 years prior to enrolment) mean serum ferritin (MSF), spot-ferritin values and liver iron content (LIC) measured using MRI and liver biopsy. Thirty-two SCD patients (median age 15 years) with transfusional iron overload were recruited from two U.S. institutions. Long-term MSF and spot-ferritin values significantly correlated with LIC by MRI-R2* (r = 0·77, P < 0·001; r = 0·82, P < 0·001, respectively). LIC by MRI-R2* had strong positive correlation with LIC by liver biopsy (r = 0·98, P < 0·001) but modest inverse correlation with cardiac MRI-T2* (r = -0·41, P = 0·02). Moderate to severe transfusional iron overload in SCD was not associated with aberrations in other measures of cardiac function based on echocardiogram or serum biomarkers. Our results suggest that SCD patients receiving chronic transfusions may not demonstrate significant cardiac iron loading irrespective of ferritin trends, LIC and erythropoiesis suppression.

Severe cardiac iron toxicity in two adults with sickle cell disease

“…A recent study reported 32 children with SCD undergoing chronic transfusion therapy who did not develop evidence of significant cardiac iron overload . However, in the two adult patients that we present, we show that ongoing transfusions can lead to significant cardiac damage.…”

Deferasirox in children with transfusion‐dependent thalassemia or sickle cell anemia: A large cohort real‐life experience from Turkey (REACH‐THEM)

“…Although iron-related cardiac morbidity is generally absent in patients with SCA, iron overload is still associated with several morbidities including pain crisis, high hospitalization rates, end-organ damage as well as mortality. [6][7][8][9][10] The effect of higher dosing was evident in our study. Although patients were given higher deferasirox doses when they had higher baseline serum ferritin levels, mean values usually remained below30 mg/kg/d even in patients with serum ferritin levels >2500 μg/L at baseline.…”

“…Our study has also observed a considerable increase in the proportion of patients with serum ferritin levels <1000 μg/L from baseline to end of study, thus, potentially giving patients the opportunity of more favorable future outcomes. Although iron‐related cardiac morbidity is generally absent in patients with SCA, iron overload is still associated with several morbidities including pain crisis, high hospitalization rates, end‐organ damage as well as mortality …”

“…The deleterious effects of iron overload in SCA have also been established, with observations of increased pain crisis, hospitalization rates, end-organ morbidity, and mortality; although with notable absence of cardiac siderosis and associated morbidity. [6][7][8][9][10] Iron overload can also affect growth and development in children with TDT and SCA further confirming the need for effective therapy of this secondary condition as early as possible. 1,11 Data from randomized clinical trials have confirmed the efficacy and safety of the oral iron chelator, deferasirox, in both TDT and SCA, including patients as young as 2 years of age treated for up to 5 years.…”

“…Thus, prompt diagnosis and effective management of iron overload in childhood can ensure patients do not reach such critical iron toxicity levels and avoid often irreversible morbidity. The deleterious effects of iron overload in SCA have also been established, with observations of increased pain crisis, hospitalization rates, end‐organ morbidity, and mortality; although with notable absence of cardiac siderosis and associated morbidity . Iron overload can also affect growth and development in children with TDT and SCA further confirming the need for effective therapy of this secondary condition as early as possible …”