How we manage iron overload in sickle cell patients

Abstract

Summary 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.

MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation

“…Interventions like chelate therapy may be initiated to protect the patients from late complications (ie, cardiac dysfunction or endocrinopathies, which may lead to growth disturbances or incomplete puberty). 5,24,25 Although it is not a standard for pediatric patients after SCT lately, but as most of our patients them showing very high SF levels (7000 µg/L up to 14 000 µg/L) and a severe course of GvHD SF was lower in the remaining four patients, revealing lighter courses of GvHD (about the dimension of values from other patients without GvHD). SF levels were measured nearly continuously to be >1000 µg/L when associated with increased CRP SF measurements during these short periods therefore seem not to be very reliable for assessing LIC, which is in agreement with other publications.…”

“…Our observation nevertheless shows that there are substantial amounts of iron incorporated even within 1 year after SCT. Interventions like chelate therapy may be initiated to protect the patients from late complications (ie, cardiac dysfunction or endocrinopathies, which may lead to growth disturbances or incomplete puberty) . Although it is not a standard for pediatric patients after SCT lately, but as most of our patients (17/23) revealed iron overload according to Angelucci et al (eLIC >7 mg/g Fe 2+ ), it is worth considering the indication for chelate therapy individually.…”

“…Although it is not a standard for pediatric patients after SCT lately, but as most of our patients (17/23) revealed iron overload according to Angelucci et al (eLIC >7 mg/g Fe 2+ ), it is worth considering the indication for chelate therapy individually. However, an initiation must be carefully considered, taking into account the long‐term administration and the chelate's side effects, and simple SF determination does not seem to be accurate enough.…”

“…23) revealed iron overload according to Angelucci et al23 (eLIC >7 mg/g Fe 2+ ), it is worth considering the indication for chelate therapy individually. However, an initiation must be carefully considered, taking into account the long-term administration and the chelate's side effects,24,25 and simple SF determination does not seem to be accurate enough.Our study clearly shows that immune responses are influencing SF values whereas MR-Fe values are not affected to that extent. The individual follow-up evaluation plots of CRP and SF revealed simultaneous peaks of both markers during the period of SCT.…”

Mouse Models of Pain in Sickle Cell Disease

“…Due to their increased adhesiveness and altered shape, sickle RBCs cluster together and adhere to the endothelium and other cellular entities, occluding capillaries and blocking blood supply to the organs, which causes organ damage and vaso-occlusive crises (VOC) exemplified by the worst symptoms of acute pain (Ballas, Gupta, & Adams-Graves, 2012;Gupta, Msambichaka, Ballas, & Gupta, 2015;NHLBI, 2014;Tran, Gupta, & Gupta, 2017). Thus, SCD pathophysiology is complex, including inflammation, oxidative stress, hypoxia/reperfusion injury, reduced nitric oxide bioavailability, iron overload, hemolytic anemia, and VOC (Coates & Wood, 2017;Frenette, 2002;Gladwin et al, 2010;Hebbel, Osarogiagbon, & Kaul, 2004;Thein, Igbineweka, & Thein, 2017;Ware et al, 2017). This complex pathobiology of SCD is manifested in organ damage, reduced survival, and pain.…”