Nursing Considerations in the Management of Patients with Chronic Transfusional Iron Overload
Nurses play a crucial role in monitoring and managing patients who develop transfusion- related iron overload from receiving red blood cell (RBC) transfusions for chronic anemia.1 Iron overload is a “silent killer” in that it damages organs long before a patient experiences clinical symptoms.1 Understanding iron overload is critical to preventing life-threatening consequences, including end-organ damage, among patients most at risk1: those with beta-thalassemia, sickle cell disease (SCD), myelodysplastic syndromes (MDS), and other rare anemias (eg, Diamond Blackfan).
This article addresses the most common diseases in which iron overload can be problematic: betathalassemia, SCD, and MDS. Discussed are the cellular and molecular mechanisms of iron metabolism; the pathophysiology of beta-thalassemia, SCD, and MDS; the development of chronic transfusional iron overload; signs and symptoms of the condition; monitoring patients; the role of nurses in iron chelation therapy; medications used to treat iron overload; and improving patient management, patient education, and adherence to therapy. Case histories and resources for healthcare providers and patients are included.
THE ROLE OF IRON IN THE BODY
Iron plays an essential role in physiologic processes such as respiration and DNA synthesis. The human body has many mechanisms to absorb, transfer, and store iron, but none to excrete it. When the human body is in normal iron balance, 1 mg to 2 mg of iron enters and is lost daily, leaving only trace amounts of circulating iron. Dietary iron is absorbed 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 hemoglobin and mature red cells and stored in the liver, ready to be mobilized for reuse.1,2
Chronic Transfusional Iron Overload
Many patients with beta-thalassemia, SCD, or MDS receive regular transfusions with RBCs as supportive therapy to improve their hemoglobin levels.1 Each unit of RBCs transfused contains 200 mg to 250 mg of iron; therefore, a patient who receives two units per month will accumulate 5 g to 6 g of iron annually.1 The primary complication that results from these frequent blood transfusions is chronic iron overload,3 which can occur after as few as 10 transfusions (ie, 20 units of RBCs).1
Normally, iron ions bound to plasma transferrin circulate within the body, accumulating within cells in the form of ferritin. Iron overload occurs when transferrin becomes saturated, increasing levels of non–transferrin-bound iron (NTBI). As high levels of toxic NTBI accumulate in the blood, they are absorbed into the surrounding tissues, leading to increased pools of unbound iron. This excess iron initially accumulates in the reticuloendothelial system, then the liver, heart, pancreas, pituitary gland, and parathyroid glands.1,2
Iron overload has serious clinical sequelae: if left untreated, transfusional hemosiderosis—accumulation of iron in the heart, liver, and endocrine glands—can result in organ compromise and, eventually, death.4 The consequences of iron deposition vary; the pituitary, thyroidal, gonadal, heart, liver, and pancreas are the most common glands and organs affected.
Hemoglobin disorders are hereditary and consist primarily of the thalassemias and SCD. Approximately 7% of the world's population are carriers of hemoglobin disorders; 300,000 to 500,000 children are born annually worldwide with the most severe forms of the disease.5 In chronically transfused patients with thalassemia and SCD, mortality is three times greater than in the general population of the United States. The most common cause of morbidity is iron overload-induced cardiomyopathy.6
Normal adult hemoglobin is made up of two alpha and two beta chains folded onto each other and held together by the heme group containing iron. Oxygen binds onto the iron molecule. Production of normal hemoglobin may be partly or completely suppressed due to inheritance of mutations or deletions in the gene responsible for the synthesis of one or more globin chains; beta-thalassemia refers to the affected globin chain.7
Beta-thalassemia is classified into two types, depending on symptom severity: thalassemia major (also known as Cooley's anemia), which is more severe, and thalassemia intermedia.7 Inheriting two defective beta-globin genes can result in ineffective erythropoiesis, leading to severe, life-threatening anemia, which usually presents in the first year of life and, if not treated, can be fatal during infancy or childhood.3 Primary treatment is transfusions with RBCs,3 which relieve severe anemia, suppress compensatory bone marrow hyperplasia, and prolong life.8
Thalassemia is most prevalent in the Mediterranean basin, the Middle East, Southern and Eastern Asia, the South Pacific, and South China, where reported carrier rates range from 2% to 25%.5 An estimated 1000 individuals are living with thalassemia major in the US.9 Signs and symptoms of beta-thalassemia are evident within the first 2 years of life and include life-threatening anemia, failure to thrive, and jaundice.7
Sickle Cell Disease
Sickle cell disease is a group of inherited genetic disorders in which hemoglobin polymerizes when deoxygenated, leading to hemolysis, blood vessel obstruction by sickled RBCs, and tissue hypoxia.10 Two-thirds of patients have SCD-SS, in which a child inherits a sickle (S) gene from each parent.11 Patients with SCD suffer chronic and episodic pain, reduced quality of life, and life-threatening complications, including stroke.10
Sub-Saharan Africa accounts for more than 70% of births
affected by SCD.5 Approximately 2000 infants with SCD
are identified by neonatal screening programs in the US
annually.11 Timely diagnostic testing, parental education,
and comprehensive care can markedly reduce morbidity
and mortality from SCD in infancy and early childhood.11
Increasingly, hospitals are adopting recommendations that
chronic transfusions be instituted for risk of stroke in
children with SCD, increasing the need for iron