Iron is absorbed from the gastrointestinal (GI) tract from food and stored in the liver in the form of ferritin. When needed by the body, the ferritin is released into the bone marrow to help make new red blood cells. When the red blood cells reach the end of their life cycle and undergo hemolysis, iron from those cells can be recycled and reused. If iron stores become depleted, either due to loss of blood, lack of adequate iron intake in the diet, or the lack of the body to absorb iron from the GI tract, iron-deficiency anemia (IDA) can occur. This can result in inadequate provision of oxygen to the body tissues and organs, leading to multiple health issues. Although there can be other causes of anemia, IDA is the most common cause worldwide. The estimated prevalence of IDA in North America is 2.9%.
Common causes of IDA can include menstruation, pregnancy, breastfeeding, chronic kidney disease (CKD), major surgery, physical trauma, GI diseases (ulcerative colitis, Crohn disease, celiac disease, peptic ulcer disease), GI malignancies, bariatric procedures, and vegetarian or vegan diets. There are multiple other less common causes of IDA as well. Efforts to identify and treat the cause(s) are necessary.
Blood tests are used to diagnose IDA. Results of laboratory tests will demonstrate the following: low hemoglobin (hgb), low mean cellular volume (MCV), low serum iron, low ferritin, low iron saturation, high transferrin, and high total iron-binding capacity (TIBC). When an individual is found to be anemic, as demonstrated by a low hgb, the next step is to look at the ferritin levels. There are different recommendations for the cut-off value for serum ferritin levels to define IDA proposed by different professional societies. The World Health Organization (WHO) recommends less than 12 ng/mL for healthy individuals aged under of 5 years, and less than 15 ng/mL for healthy individuals aged 5 years and above. For individuals with infection or inflammation, the levels increase to less than 30 ng/mL and less than 70 ng/mL for the same groups. The National Heart, Lung, and Blood Institute (NHLBI) recommends a cut-off level for ferritin at less than 10 ng/mL. The American Gastroenterological Association (AGA) recommends a cut-off level for ferritin at less than 45 ng/mL.
Once IDA has been identified, treatment can begin. Identifying the cause of the IDA can occur at the same time that the IDA is being treated. Treatment is usually begun with oral iron supplementation. If the individual is unable to tolerate oral iron supplementation, has a documented contraindication to oral iron supplementation, or has a documented nonresponse to oral iron supplementation, then erythropoiesis-stimulating agents (ESAs) and/or intravenous (IV) iron can be ordered. ESAs work by helping the bone marrow make more red blood cells (RBCs). Individuals who are on hemodialysis for end-stage renal disease (ESRD) can receive these medications while they are undergoing their dialysis treatments. If the anemia is severe enough that the individual has symptoms (e.g., fatigue, weakness, dizziness, lightheadedness), then the individual may require transfusions of blood products.
Ferric carboxymaltose (
Injectafer) is a colloidal iron (III) hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron.
Ferric derisomaltose (
Monoferric) is a complex of iron (III) hydroxide and derisomaltose, an iron carbohydrate oligosaccharide that releases iron. Iron binds to transferrin for transport to erythroid precursor cells to be incorporated into hemoglobin.
Ferumoxytol (
Feraheme) consists of a superparamagnetic iron oxide that is coated with a carbohydrate shell, which helps to isolate the bioactive iron from plasma components until the iron-carbohydrate complex enters the reticuloendothelial system macrophages of the liver, spleen, and bone marrow. The iron is released from the iron-carbohydrate complex within vesicles in the macrophages. Iron then either enters the intracellular storage iron pool (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into hemoglobin.
Iron dextran (
INFeD) is a complex of ferric hydroxide and dextran that releases iron into the circulation in order to replenish hemoglobin and depleted iron stores.
Iron sucrose (
Venofer) is an aqueous complex of
polynuclear iron (III) hydroxide in sucrose. Following intravenous administration, iron sucrose (
Venofer) is dissociated into iron and sucrose and the iron is transported as a complex with transferrin to target cells including erythroid precursor cells. The iron in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
Sodium ferric gluconate complex in sucrose (
Ferrlecit) is a stable macromolecular complex and is used to replete the body content of iron.
OFF-LABEL INDICATIONSThere may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
