Transfusional Iron Overload in a Cohort of Children with Sickle Cell Disease: Impact of Magnetic Resonance Imaging, Transfusion Method, and Chelation

Abstract

BackgroundTransfusions prevent a number of complications of sickle cell disease (SCD), but cause inevitable iron loading. With magnetic resonance imaging (MRI), liver iron can be monitored noninvasively. Erythrocytapheresis can limit iron loading and oral chelation provides a more tolerable alternative to subcutaneous administration. The impact of these factors on control of iron burden in SCD has not been well studied.ProcedureIron monitoring practices, chelation use, and transfusion methods were assessed in our cohort of pediatric patients with SCD receiving chronic transfusion. The impact of these factors on iron burden was assessed.ResultsAmong 84 subjects, the proportion that underwent appropriate liver iron concentration (LIC) assessment rose from 21% before to 81% after implementation of R2‐MRI in 2006. Among subjects with at least two R2‐MRI examinations, median LIC improved (13.2–7.9 mg/g dw, P = 0.027) from initial to final study. Most (67.9%) subjects initially received simple transfusions and subsequently transitioned to erythrocytapheresis. After switching, LIC improved from 13.1 to 4.3 mg/g dw (P < 0.001) after a median of 2.7 years and ferritin improved (2,471–392 ng/ml, P < 0.001) after a median of 4.2 years. Final serum ferritin and LIC correlated negatively with the proportion of transfusions administered by erythrocytapheresis and chelation adherence.ConclusionsRoutine liver R2‐MRI should be performed in individuals with SCD who receive chronic red cell transfusions. Adherence with chelation should be assessed regularly and erythrocytapheresis utilized when feasible to minimize iron loading or reduce iron stores accumulated during periods of simple transfusion.

Increased complications of chronic erythrocytapheresis compared with manual exchange transfusions in children and adolescents with sickle cell disease

“…reported relatively stable ferritin concentrations in children receiving MET, whereas Stanley et al. found that aRBCX recipients had a greater LIC reduction than simple transfusion recipients, measured by MRI . Although we did not find a significant difference in serum ferritin between the aRBCX and MET groups, we found that children who had a chelation holiday received a greater percentage of their transfusion therapy by aRBCX, and were more adherent to appointments and chelation therapy.…”

“…23 Savage et al 24 and Aloni et al 25 reported relatively stable ferritin concentrations in children receiving MET, whereas Stanley et al found that aRBCX recipients had a greater LIC reduction than simple transfusion recipients, measured by MRI. 26 Although we did not find a significant difference in serum ferritin between the aRBCX and MET groups, we found that children who had a chelation holiday received a greater percentage of their transfusion therapy by aRBCX, and were more adherent to appointments and chelation therapy. Our results suggest that patient factors, including adherence to the transfusion schedule and prescribed medications, may be as important in controlling Hb S and ferritin levels as the type of transfusion therapy employed.…”

Vascular access for red blood cell exchange

“…Iron overload is a common complication of simple transfusion regimens for chronic therapy . It is often severe enough to require iron chelation.…”

“…It is often severe enough to require iron chelation. Because automated RBC exchange removes older RBCs from the patient's system, it is less likely to cause iron overload and may even reduce iron overload in patients who previously received treatment on a simple transfusion regimen . Patients who do not benefit from or are not compliant with iron chelation may be better served by being switched to automated exchange.…”

Sickle cell disease: when and how to transfuse

“…If used as the initial form of transfusion, it may prevent iron overload and can allow cessation of iron chelation in well-chelated patients. 19,20 A small proportion of patients (particularly those with a low baseline Hb level) will accumulate iron at a low rate even with RCE and may need concurrent iron chelation at a reduced intensity. Automated exchanges do require more blood than manual exchange or simple transfusion but are not associated with increased rates of alloimmunization.…”