Nurses play a crucial role in monitoringand managing patients who develop transfusion-related iron overload from receivingred blood cell (RBC) transfusions forchronic anemia.1 Iron overload is a “silentkiller” in that it damages organs long beforea patient experiences clinical symptoms.1Understanding iron overload is critical topreventing life-threatening consequences,including end-organ damage, amongpatients most at risk1: those with beta-thalassemia,sickle cell disease (SCD),myelodysplastic syndromes (MDS), andother rare anemias (eg, DiamondBlackfan).
This article addresses the most commondiseases in which iron overload can beproblematic: betathalassemia, SCD, andMDS. Discussed are the cellular and molecularmechanisms of iron metabolism; thepathophysiology of beta-thalassemia, SCD,and MDS; the development of chronictransfusional iron overload; signs and symptomsof the condition; monitoring patients;the role of nurses in iron chelation therapy;medications used to treat iron overload; andimproving patient management, patienteducation, and adherence to therapy.Case histories and resources for healthcareproviders and patients are included.
THE ROLE OF IRON IN THE BODY
Iron plays an essential role in physiologic processes such asrespiration and DNA synthesis. The human body has manymechanisms to absorb, transfer, and store iron, but noneto excrete it. When the human body is in normal ironbalance, 1 mg to 2 mg of iron enters and is lost daily, leavingonly trace amounts of circulating iron. Dietary iron isabsorbed and circulates in plasma bound to a globulin,transferrin, where it is utilized in muscle and bone marrow.Most of the iron, however, is incorporated into hemoglobinand mature red cells and stored in the liver, ready to bemobilized for reuse.1,2
Chronic Transfusional Iron Overload
Many patients with beta-thalassemia, SCD, or MDS receiveregular transfusions with RBCs as supportive therapy toimprove their hemoglobin levels.1 Each unit of RBCstransfused contains 200 mg to 250 mg of iron; therefore,a patient who receives two units per month will accumulate5 g to 6 g of iron annually.1 The primary complication thatresults from these frequent blood transfusions is chroniciron overload,3 which can occur after as few as 10 transfusions(ie, 20 units of RBCs).1
Normally, iron ions bound to plasma transferrin circulatewithin the body, accumulating within cells in the form offerritin. Iron overload occurs when transferrin becomessaturated, increasing levels of non–transferrin-bound iron(NTBI). As high levels of toxic NTBI accumulate in theblood, they are absorbed into the surrounding tissues, leadingto increased pools of unbound iron. This excess ironinitially accumulates in the reticuloendothelial system, thenthe liver, heart, pancreas, pituitary gland, and parathyroidglands.1,2
Iron overload has serious clinical sequelae: if left untreated,transfusional hemosiderosis—accumulation of iron in theheart, liver, and endocrine glands—can result in organcompromise and, eventually, death.4 The consequences ofiron deposition vary; the pituitary, thyroidal, gonadal,heart, liver, and pancreas are the most common glands andorgans affected.
Hemoglobin disorders are hereditary and consist primarilyof the thalassemias and SCD. Approximately 7% of theworld’s population are carriers of hemoglobin disorders;300,000 to 500,000 children are born annually worldwidewith the most severe forms of the disease.5 In chronicallytransfused patients with thalassemia and SCD, mortalityis three times greater than in the general population ofthe United States. The most common cause of morbidityis iron overload-induced cardiomyopathy.6
Normal adult hemoglobin is made up of two alpha andtwo beta chains folded onto each other and held togetherby the heme group containing iron. Oxygen binds ontothe iron molecule. Production of normal hemoglobin maybe partly or completely suppressed due to inheritance ofmutations or deletions in the gene responsible for the synthesisof one or more globin chains; beta-thalassemia refersto the affected globin chain.7
Beta-thalassemia is classified into two types, dependingon symptom severity: thalassemia major (also known asCooley’s anemia), which is more severe, and thalassemiaintermedia.7 Inheriting two defective beta-globin genescan result in ineffective erythropoiesis, leading to severe,life-threatening anemia, which usually presents in the firstyear of life and, if not treated, can be fatal during infancyor childhood.3 Primary treatment is transfusions withRBCs,3 which relieve severe anemia, suppress compensatorybone marrow hyperplasia, and prolong life.8
Thalassemia is most prevalent in the Mediterranean basin,the Middle East, Southern and Eastern Asia, the SouthPacific, and South China, where reported carrier rates rangefrom 2% to 25%.5 An estimated 1000 individuals are livingwith thalassemia major in the US.9 Signs and symptoms ofbeta-thalassemia are evident within the first 2 years of lifeand include life-threatening anemia, failure to thrive, andjaundice.7
Sickle Cell Disease
Sickle cell disease is a group of inherited genetic disordersin which hemoglobin polymerizes when deoxygenated,leading to hemolysis, blood vessel obstruction by sickledRBCs, and tissue hypoxia.10 Two-thirds of patients haveSCD-SS, in which a child inherits a sickle (S) gene fromeach parent.11 Patients with SCD suffer chronic and episodicpain, reduced quality of life, and life-threatening complications,including stroke.10
Sub-Saharan Africa accounts for more than 70% of birthsaffected by SCD.5 Approximately 2000 infants with SCDare identified by neonatal screening programs in the USannually.11 Timely diagnostic testing, parental education,and comprehensive care can markedly reduce morbidityand mortality from SCD in infancy and early childhood.11Increasingly, hospitals are adopting recommendations thatchronic transfusions be instituted for risk of stroke inchildren with SCD, increasing the need for ironchelation.12