How we manage iron overload in sickle cell patients

Abstract

Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging.

Keywords: anaemia; chelator; iron overload; management; sickle cell disease.

Figure 1

Temporal partitioning of total body iron (liver iron concentration, LIC) into pancreas and heart in a chronically transfused sickle cell patient who was minimally adherent to chelation. Serial MRI measurements of the organ iron are plotted (left axis) as fold change relative to normal. The pancreas iron (normal = 27 Hz) reaches the level associated with glucose intolerance (100 Hz) at 18.8 years of age, well before the cardiac T2* drops below 20 ms at about 21 years. The left ventricular ejection fraction (LVEF) by magnetic resonance imaging (MRI) drops at age 23 years.

Figure 2

Ferritin levels in patients with sickle cell disease show very broad scatter. The liver iron concentration (LIC) levels at 3, 7 and 20 mg/g dry weight liver correspond to levels that have been related to ferritin in Table IV (Taher et al, 2015).

Figure 3

non-transferrin bound iron (NTBI) levels drop quickly after starting infusion of deferoxamine (DFO) and return quickly when DFO is stopped (Porter, et al 1996). NTBI/labile plasma iron, which are free to enter organs through non-regulated ion transporters, are rapidly reduced when chelators are circulating and, until total iron excess is reduced, return when there is no chelator present.