Iron-Deficiency Anemia IDA is classically a microcytic and hypochromic anemia, reflected as a decreased MCV and mean corpuscular Hb concentration (MCHC), respectively. From: Hematopathology (Second Edition), 2012 Related terms: FerritinIron Storage View all Topics Iron Deficiency Anemia In Diagnostic Pathology: Blood and Bone Marrow (Second Edition), 2018 Clinical Issues • Iron deficiency anemia is most common anemia worldwide; estimated global anemia prevalence is 24.8%, affecting > 1.62 billion people • Insidious onset, chronic, often asymptomatic • Symptoms may include fatigue, pallor, weakness, tachycardia, dyspnea on exertion • Diagnosis of iron deficiency anemia should be based on panel of tests, not on any single test • Low serum ferritin is pathognomonic of iron deficiency anemia • Serum transferrin saturation < 16% supports diagnosis of iron deficiency • Oral ferrous iron salt (ferrous sulfate) supplementation to all patients with iron deficiency • Parenteral iron should be given to patients who cannot take or are refractory to oral iron supplement • Red blood cell transfusion should be given to patients with symptomatic severe iron deficiency anemia to rapidly correct hypoxia and iron deficiency • Excellent prognosis except in patients with underlying disease Hematology and hemostasis in the pediatric, geriatric, and pregnant populations Linda H. Goossen, in Rodak's Hematology (Sixth Edition), 2020 Iron deficiency anemia. Iron deficiency anemia is the most common pediatric hematologic disorder and the most common cause of anemia in childhood.22,23 Iron deficiency anemia is more prevalent in premature infant because the majority of the placental transfer of maternal iron occurs late in the third trimester.4 The occurrence of iron deficiency anemia in infants has decreased in the United States because of iron fortification of infant formula and increased rates of breastfeeding.24 However, the prevalence is still 2% in toddlers 1 to 2 years of age and 3% in children 3 to 5 years of age25 and is related to early introduction and excessive intake of whole cow’s milk.20,25 Chapter 17 provides an in-depth discussion of iron deficiency anemia. Circulatory, Reticuloendothelial, and Hematopoietic Disorders Anne L. Grauer, in Ortner's Identification of Pathological Conditions in Human Skeletal Remains (Third Edition), 2019 Iron-Deficiency Anemia IDA, or acquired anemia, is the most common type of anemia found globally. It is associated with the presence of microcytic and hypochromic RBC, along with depressed levels of total body iron (Camaschella, 2015). Bone changes in IDA tend to be clinically mild. Changes in the skull vault resemble those described for other anemias, i.e., radiographically recognizable enlargement of the diploë with vertical orientation of the trabeculae. Aksoy et al. (1966) report that generalized granular osteoporosis of the skull and long bones might also appear in some patients. IDA has received the greatest attention as a diagnostic option for porous hypertrophic lesions of the skull in the paleopathological record. However, the tendency for this anemia to produce only limited skeletal involvement has raised questions about the legitimacy of the diagnosis. Importantly, a wide range of conditions invoke an anemic response by the body, rendering the isolation of the cause of hypertrophic lesions extremely difficult (Table 14.2). Table 14.2. Causes of Iron Deficiency and Iron-Deficiency Anemia Environmental Insufficient dietary intake Dietary restrictions or predilection (grain intensive, vegetarian, vegan, etc.) Genetic Iron-refractory iron-deficiency anemia Pathologic Decreased absorption Atrophic gastritis Celiac sprue Helicobacter pylori infection Inflammatory bowel diseases Parasitic infestation Chronic blood loss Gastrointestinal tract Benign and malignant tumors Diverticulitis Erosive gastritis Esophagitis Hookworm infestation Peptic ulcer Genitourinary system Intravascular hemolysis Heavy mensis or menorrhagia Systemic bleeding Chronic schistosomiasis Hemorrhagic telangiectasia Physiologic Increased demand for iron Infancy Rapid growth (adolescence) Menstruation Pregnancy Source: After Camaschella (2015). Pediatric Transfusion in Developing Countries Kenneth A. Clark MD, MPH, in Handbook of Pediatric Transfusion Medicine, 2004 Nutritional Anemia Iron deficiency anemia is highly prevalent in many developing countries. The WHO estimates that as many as 50% of children in developing countries have iron-deficiency anemia (WHO 2001). Rural populations with more restricted resources and lower educational levels may be more severely affected than urban populations. Infants who have been breast-fed for more than 4 to 6 months are particularly susceptible if their diets are not supplemented with foods rich in iron or dietary supplements. In some areas, the use of iron supplements is limited by resources. Inadequate dietary intake of vitamin B12 or folate also contributes to pediatric anemia. Dietary insufficiencies are often compounded by additional illnesses such as diarrheal diseases that further impair intestinal absorption. Disorders of Red Blood Cells James W. Little DMD, MS, ... Nelson L. Rhodus DMD, MPH, in Little and Falace's Dental Management of the Medically Compromised Patient (Eighth Edition), 2013 Iron Deficiency Anemia Iron deficiency anemia is a microcytic anemia (Figure 22-2) that can be caused by excessive blood loss, poor iron intake, poor iron absorption, or increased demand for iron. Blood loss may occur with menstruation or be caused by bleeding from the gastrointestinal tract. Poor intake is more common in children who live in developing countries, where cereals and formula fortified with iron are not readily available. Malabsorption of iron can result from gastrectomy or intestinal disease that reduces absorption of iron from the duodenum and the jejunum. Increased demand is associated with chronic inflammation (autoimmune disease). In women, menstruation and pregnancy contribute to the development of iron deficiency anemia. The repeated loss of blood associated with menses can lead to depletion of iron, resulting in a mild state of anemia. During pregnancy, the expectant mother experiences an increased demand for additional iron and vitamins to support the growth of her fetus, and unless sufficient amounts of these nutrients have been provided in some form, she may become anemic. Approximately 20% of pregnant women have iron deficiency anemia.11 Also, 30% to 60% of persons with rheumatoid arthritis (who more commonly are women) have this type of anemia.12 By contrast, mild anemia in men usually indicates the presence of a serious underlying medical problem (e.g., gastrointestinal bleeding, malignancy). Under normal physiologic conditions, men lose little iron, and because iron can be stored for months, iron deficiency anemia is rare in men. Therefore, any man who is found to be anemic should be promptly referred for medical evaluation. Red-Blue Lesions In Oral Pathology (Sixth Edition), 2012 Iron Deficiency Anemia Etiology Iron deficiency anemia is a rather common anemia caused by iron deficiency. This deficiency may be due to inadequate dietary intake; impaired absorption caused by a gastrointestinal malady; chronic blood loss caused by such problems as excessive menstrual flow, gastrointestinal bleeding, or aspirin ingestion; and increased demand as experienced during childhood and pregnancy. Clinical Features This relatively prevalent form of anemia predominantly affects women. In addition to the clinical signs and symptoms associated with anemias in general, iron deficiency anemia may result in brittle nails and hair and koilonychia (spoon-shaped nails). The tongue may become red, painful, and smooth. Angular cheilitis may also be seen. In addition to iron deficiency, the Plummer-Vinson (Paterson-Kelly) syndrome includes dysphagia, atrophy of the upper alimentary tract, and a predisposition to the development of oral cancer. Diagnosis Laboratory blood studies show slightly to moderately reduced hematocrit and reduced hemoglobin level. The RBCs are microcytic and hypochromic. The serum iron level is also low, but the total iron-binding capacity (TIBC) is elevated. Treatment Recognition of the underlying cause of iron deficiency anemia is necessary to treat this condition effectively. Dietary iron supplements are required to elevate hemoglobin levels and replenish iron stores once an underlying cause has been defined and treated. Sports Medicine and Adaptive Sports Christopher W. Mcmullen, ... Mark A. Harrast, in Braddom's Physical Medicine and Rehabilitation (Sixth Edition), 2021 Anemia The three most common causes of anemia in the athlete are iron deficiency anemia (IDA), physiologic anemia (pseudoanemia), and foot-strike hemolysis. IDA is most common in menstruating women, and female athletes can be more prone to developing it. The etiology is either blood loss or poor iron intake. Many athletes consume restrictive diets that can have too little iron to meet daily needs. However, a complete history and physical examination are still important to evaluate for “nonathletic” causes such as significant gastrointestinal or genitourinary blood losses. Usually a serologic work-up is diagnostic and includes complete blood count (CBC), serum ferritin, and total iron binding capacity (TIBC). The CBC will show a microcytic anemia.130 Serum ferritin levels that are less than 30 ng/mL in athletes are considered suggestive of IDA.74 The TIBC will be elevated. If IDA is diagnosed, a trial of oral iron supplementation (typically ferrous sulfate or ferrous gluconate, 325 mg three times daily) is undertaken.45 Iron is best absorbed in an acidic environment, so it is concomitantly administered with vitamin C, usually for a 2- to 3-month course. Physiologic anemia is considered a pseudoanemia seen commonly in endurance athletes. Endurance athletes tend to have a lower hemoglobin concentration than the general population because of plasma volume expansion with a dilutional effect. It is an adaptation to exercise and is not considered to inhibit athletic performance. It generally normalizes with training cessation of 3 to 5 days. If IDA is ruled out, there is no necessary treatment. Foot-strike hemolysis refers to red blood cell destruction in the feet from running impact. However, intravascular hemolysis is seen in swimmers, cyclists, and runners, but whether or not actual mechanical red blood cell trauma is the source is questionable. Possible reasons are intramuscular destruction, osmotic stress, and membrane lipid peroxidation caused by free radicals released by activated leukocytes. Intravascular hemolysis can even be regarded as a physiologic means to provide heme and proteins for muscle growth in athletes.213 In general, the hemolysis is mild, and treatment is rarely required. Volume 2 Gerard E. Mullin MD, in Textbook of Natural Medicine (Fifth Edition), 2020 Iron Iron deficiency anemia is very common in IBD, largely because of chronic blood loss through the gut.60 Serum ferritin levels are the most useful indices of iron status. A serum ferritin concentration of greater than 55 ng/mL indicates adequate iron reserves in bone marrow, whereas a concentration of less than 18 ng/mL is highly predictive of iron deficiency (see Chapter 23 for further discussion). The clinician should attempt to increase the patient’s iron stores by improving absorption, as with supplemental vitamin C, rather than through direct iron supplementation, which promotes intestinal infection.71 Red Blood Cell/Hemoglobin Disorders Steven H. Kroft MD, Sara A. Monaghan MD, in Hematopathology (Second Edition), 2012 Clinical Features IDA ranges from mild to profound, with Hb levels as low as 2 g/dL in the most severe cases. IDA is classically a microcytic and hypochromic anemia, reflected as a decreased MCV and mean corpuscular Hb concentration (MCHC), respectively. However, the MCV may be normal in early iron deficiency; the degree of microcytosis roughly correlates with the degree of anemia. Likewise, the MCHC may be normal in early iron deficiency when only a minority of cells are hypochromic. Iron Deficiency Anemia—Fact Sheet Definition ▪ Anemia owing to inadequate iron supply Incidence and Location ▪ Most common cause of anemia worldwide Morbidity and Mortality ▪ Reduced quality of life and reduced productivity ▪ Probably increased maternal and fetal–neonatal morbidity and mortality ▪ Probably reduced cognitive development in children Gender, Race, and Age Distribution ▪ Increased incidence in infants, children, women of childbearing age, and impoverished populations, particularly in underdeveloped countries ▪ Increased incidence in some minorities compared with white population in the United States Clinical Features ▪ General signs and symptoms of chronic anemia ▪ Angular cheilitis, glossitis, pica, koilonychia, and esophageal webs Prognosis and Therapy ▪ Oral iron supplementation ▪ Parenteral iron in patients with uncontrolled blood loss, intolerance to oral iron, or intestinal malabsorption Most signs and symptoms are those seen in any form of anemia, such as fatigue, dyspnea, and pallor of skin and mucous membranes. Because the anemia develops over a protracted period and compensatory mechanisms have ample time to develop, anemia resulting from iron deficiency is surprisingly well tolerated, even when extremely severe. Pica, koilonychia (i.e., spoon-shaped nails), and esophageal webs are rare but have a strong association with IDA. Angular cheilitis and atrophic glossitis are also seen with IDA but are not specific. Pathologic Features The characteristic findings on the peripheral blood film are small (microcytic), underhemoglobinized (hypochromic) RBCs with variability in size (anisocytosis) and abnormal shapes (poikilocytosis; Figure 1-10). Elliptocytes are prominent poikilocytes in IDA; often they are long and narrow (pencil cells). Prekeratocytes are usually evident and are recognized as red cells with sharp-edged, submembranous vacuoles and preserved central pallor (see Figure 1-10). Target cells, teardrop cells, very small hypochromic microcytes, and various nonspecific poikilocytes are also common. Occasional red cell fragments may be observed, but they are not prominent. Thrombocytosis is common, but platelet counts may also be normal or reduced. Variations from the typical findings occur when there has been recent partial repletion of iron or when additional factors, such as Cbl or folate deficiency, are also contributing to anemia. Iron Deficiency Anemia—Pathologic Features Peripheral Blood ▪ Hypochromic, microcytic red blood cells ▪ Anisocytosis ▪ Lack of polychromasia ▪ Poikilocytosis, including elliptocytes, prekeratocytes, and target cells Bone Marrow ▪ Mild erythroid hyperplasia ▪ Absent stainable iron on a Prussian blue stain on an aspirate smear Differential Diagnosis ▪ Thalassemia trait or thalassemia-like hemoglobinopathy ▪ Anemia of chronic disease The bone marrow in IDA may demonstrate erythroid hyperplasia, but this is generally of only a mild degree. Erythroid precursors may have scant cytoplasm with frayed cytoplasmic borders. Ancillary Studies Serum ferritin measurement is the most useful single laboratory test for iron deficiency. Serum ferritin below the lower limit of the reference range (about 12 mg/dL) is essentially diagnostic of iron deficiency. However, ferritin is an acute-phase reactant, and normal levels may be seen when iron deficiency coexists with infection, inflammation, or malignancy. However, when this occurs, the ferritin level will usually be low-normal; therefore low-normal values in an individual with an active inflammatory process support a diagnosis of iron deficiency in the appropriate setting. Ferritin levels may even be higher in patients with acute liver injury, despite iron deficiency. Measurement of serum iron alone is not useful because of diurnal fluctuations of serum iron levels and the rapid changes that may occur with dietary intake, inflammation, and blood loss. Transferrin, measured either directly or indirectly as the total iron binding capacity, is typically increased in IDA, but this response can be blunted in the presence of hypoproteinemia. The transferrin saturation (the ratio of serum iron to total iron binding capacity) is typically less than 15% in iron deficiency, but saturation levels in this range may also be seen in ACD. Increased serum soluble transferrin receptor (sTfR) is a sensitive marker of iron deficiency, reflecting increased expression of this receptor on RBC precursors as a response to depleted tissue iron. This parameter is elevated during iron-deficient erythropoiesis before the development of overt anemia. Furthermore, inflammation does not raise sTfR levels substantially. However, states with an increased mass of RBC precursors such as hemolytic anemias and ineffective erythropoiesis (e.g., megaloblastic anemia) will manifest elevated sTfR; therefore this finding is not specific for iron deficiency. When biochemical tests are equivocal, the absence of stainable iron with a Prussian blue stain performed on well-prepared marrow aspirate smear is considered to be the gold standard for the diagnosis of IDA. An iron stain performed on a bone marrow core biopsy may also be helpful, but iron can be leached out during decalcification of the bone marrow biopsy and result in the false interpretation of absent iron stores. Differential Diagnosis Other common causes of hypochromic, microcytic anemia are thalassemia and ACD. Sideroblastic anemia with microcytosis is rarer. The hematologic and biochemical tests that are useful to differentiate the major causes of microcytic anemia are listed in Table 1-3. In addition, mild anemia associated with thalassemia trait or a thalassemia-like hemoglobinopathy (e.g., Hb E) characteristically exhibits a red blood cell count greater than 5 × 1012 cells/L, which is unusual for IDA. Hb electrophoresis would help establish the diagnosis of most β-thalassemias and thalassemia-like hemoglobinopathies. Under circumstances that render the interpretation of biochemical studies for iron status particularly difficult, such as inflammation, monitoring the response of Hb or the reticulocyte count to a therapeutic trial of iron supplementation may be sufficient to confirm iron deficiency. Otherwise, any uncertainty about iron status usually can be resolved by an iron stain performed on a bone marrow aspirate smear. Pathological Conditions Efthymia Nikita, in Osteoarchaeology, 2017 8.5.4 Iron-Deficiency Anemia Iron-deficiency anemia results from reduced iron availability in the red blood cells (Box 8.5.3). Iron is an integral component of the hemoglobin molecule and its main function is the transport of oxygen to various bodily tissues. Iron-deficient red blood cells are generally small (microcytic), are pale (hypochromic), have a short life span, and are incapable of transporting oxygen efficiently (Kozłowski and Witas, 2011). The factors that may reduce iron availability include malnutrition, parasitic infestations that inhibit iron absorption, infection that makes the body withhold iron, profuse hemorrhage, or increased iron demands during growth or pregnancy (Holland & O'Brian, 1997; Stuart-Macadam, 1989; Sullivan, 2005). Box 8.5.3 Skeletal Manifestations of Iron-Deficiency Anemia (Stuart-Macadam, 1992; Sullivan, 2005) • Skull • Enlarged diploë, thinned cortical bone layer, thickened vault (PH) • Porosity of the orbital roof (CO) • Long bones • Osteoporosis With regard to diet, heme iron is found primarily in meat and it is easily absorbed through the intestine, whereas nonheme iron may be obtained through consumption of cereals, legumes, fruits, and vegetables but it is less bioavailable. Moreover, phytates, tannins, and other food compounds can bind iron into complex formations that cannot be absorbed by the intestine. Finally, calcium consumed together with iron-providing foodstuff inhibits iron absorption, whereas vitamins A and C improve it (Lynch, 1997). With respect to the role of infectious agents, it has been supported that iron-deficiency anemia results from an immune response that binds iron to prevent its use by infectious agents (Stuart-Macadam, 1992). However, although iron withholding may decrease the incidence and intensity of many infections, beyond a certain limit it actually increases host susceptibility to invading organisms (Weinberg, 1992; see also Hadley and DeCaro, 2015 for a lack of association between iron-deficiency anemia and low likelihood of infection). Regarding parasitic infections and their role in iron absorption, infection by whipworms and hookworms causes iron loss through intestinal bleeding, whereas parasites such as giardia and roundworm diminish the intestinal absorption of iron (Brooker et al., 2007; Stoltzfus et al., 1997). Finally, regarding the role of growth, infants require more iron than other age groups because of their high growth rate. As a result, maternal anemia during pregnancy increases the possibility of the offspring becoming anemic too (Allen, 1997).