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Anemia: Diagnosis and Management
Original Article
Anemia: Diagnosis and Management Sharon M. Coyer, PhD, APN, CPNP
ABSTRACT Anemia is a pathologic condition produced by a decrease in red blood cell mass or a decrease in the amount of hemoglobin. Anemia is a common occurrence in the United States. Children from some ethnic groups have a higher incidence of anemia, but anemia also can affect overweight children and children with chronic illnesses. Iron-deficiency anemia, which is the most common cause of anemia and can produce long-term developmental outcomes, continues to be prevalent in some groups of children. This article will review the procedures for taking a history, determining the etiology, and providing initial treatment for the anemia. J Pediatr Health Care. (2005) 19, 380-385.
Sharon M. Coyer is Assistant Professor, Northern Illinois University, School of Nursing, DeKalb, Ill. Reprint requests: Sharon M. Coyer, PhD, APN, CPNP, School of Nursing, Northern Illinois University, 1240 N Normal Rd, DeKalb, IL 60115; e-mail: [email protected] 0891-5245/$30.00 Copyright © 2005 by the National Association of Pediatric Nurse Practitioners. doi:10.1016/j.pedhc.2005.07.014
380
Volume 19 • Number 6
www.jpedhc.org
Anemia is a pathologic condition in which there is a decrease in red blood cell mass or a decrease in the amount of hemoglobin (Carley, 2003; Kumar, Cotran, & Robbins, 2003). Anemia is a common occurrence in the United States. As many as 20% of children have anemia, and ethnic groups may have a higher incidence, such as AfricanAmerican children (24.6%) and Hispanic children (18.4%) (Carley). Anemia may develop in overweight children (Nead, Halterman, Kaczorowski, Auinger, & Weitzman, 2004). Iron-deficiency anemia can produce long-term developmental outcomes and continues to be prevalent in some groups of children (Childs, Aukett, Darbyshire, Ilett, & Livera, 1997; Lozoff, Jimenez, Hagen, Mollen & Wolf, 2000). Anemia continues to occur in groups of children with an inadequate diet, although supplemental food programs have helped some parents provide their children with foods with higher iron content (Kahn, Binns, Chen, Tanz, & Listernick, 2002; Sherry, Bister, & Yip, 1997; Sherry, Zuguao, & Yip, 2001). Children living in high-altitude locations and some ethnic groups have different criteria for evaluating the normal hemoglobin (Hoekeleman, Adam, Nelson, Weitzman, & Wilson, 2001). If the child has a chronic condition, such as cystic fibrosis, the child may require a higher hemoglobin and hematocrit to avoid the problems associated with anemia. For nurse practitioners, the evaluation of the hemoglobin and hematocrit of a child requires not only evaluating the normal range for the child’s age but also whether the child’s hemoglobin and hematocrit has changed significantly since the last visit. This article will review the procedures for taking a history, determining the etiology, Journal of Pediatric Health Care
Anemia can be classified in two ways: by the physiologic process of red blood cell loss or by the size, color, and shape of the red blood cells.
and providing initial treatment for the anemia. PATHOPHYSIOLOGY OF ANEMIA Anemia can be classified in two ways: by the physiologic process of red blood cell loss or by the size, color, and shape of the red blood cells. The classification of anemia based on physiologic process includes several etiologies. Anemia can be caused by a decrease in red cells as a result of blood loss, increased rate of destruction of the red cell, and impaired red cell production. Blood loss occurs during acute or chronic diseases (Rudolph, Kamei, & Overby, 2002). Increased rate of destruction of red cells occurs in various hemolytic anemias, resulting from both intrinsic factors and extrinsic factors. Intrinsic abnormalities of red cell can be the result of hereditary or acquired diseases. Hereditary diseases have several etiologies. Sperocytosis and elliptocytosis are conditions causing anemia because of a disorder in the red cell membrane.Disorders in red cell enzymes, such as glucose-6-phosphate dehydrogenase and pyruvate synthesis diseases, also can cause anemia. Sickle cell anemia and thalassemia cause anemia because red cells have structural abnormalities (Kumar et al., 2003). There are extrinsic abnormalities of the red blood cell that produce anemia. Other extrinsic factors causing anemia are antibodymediated red cell destruction diseases, such blood transfusion reactions. Another extrinsic factor causing anemia are mechanical processes causing red cell destruction, such as hemolytic anemia, Journal of Pediatric Health Care
and thrombocytopenia purpura or disseminating intravascular coagulation. Anemia that is produced from impaired cell production occurs when there is a disturbance of proliferation and distribution of stem cells. This situation occurs in aplastic anemia, anemia from renal cell aplasia, and anemia from renal failure or endocrine disorders. Impaired cell production also can occur with a disturbance in maturation and proliferation of red
child with anemia. The nutritional history should include the mother’s dietary patterns if she is breastfeeding an infant. Infants, toddlers, and adolescent girls share the possibility of iron deficiency anemia resulting from nutrition and diet deficiencies. The review of the systems should include a newborn history of jaundice. The history should include an evaluation of extremity pain, blood loss, extensive bruising, petechia, travel, infection exposure, and drug use. A family history of jaundice, splenectomy, or cholecystectomy suggests a hereditary etiology for hemolytic anemia diseases (Dershewitz, 1999). The physical examination should include a comprehensive review of the plotted growth charts and a survey of the patterns of
The history should include an evaluation of extremity pain, blood loss, extensive bruising, petechia, travel, infection exposure, and drug use. cells. Impaired cell production occurs when cells have defective DNA synthesis such in vitamin B12 and folic acid anemia. Defective hemoglobin synthesis is the pathologic process for iron deficiency anemia, thalassemia, and the anemia of chronic infections (Kumar et al., 2003). DIAGNOSIS OF ANEMIA Family and Physical History The history provides valuable information for the diagnostic workup. A family history should include information about the ethnic heritage of the family, any history of anemias, splenectomy, jaundice, gallbladder disease, sickle cell trait, or thalassemia. A nutritional history is an important part of the history in the evaluation of a
growth of the child over a period of time to determine the potential for chronic anemia. The physical examination also should include an evaluation of the child for pallor, jaundice, petechiae, bruising, murmurs adenopathy, organomegaly, frontal bossing, and congenital anomalies (Dershewitz, 1999). The blood pressure, heart rate, and respiratory rate also should be evaluated using the appropriate normative values for the child’s age and height (Wong, Hockenberry, Wilson, Winkelstein, & Kline, 2003). Lack of iron stores at birth, low level of iron in the diet during growth, and blood loss all cause iron deficiency and can lead to iron deficiency anemia. Iron stores are developed during the November/December 2005 381
TABLE 1. Normal values for hemoglobin, hematocrit and mean corpuscular value Hemoglobin (g/dL)
Age (y) 0.5-1.9 2-4 5-7 8-11 12-14 Female Male 15-17 Female Male 18-49 Female Male
Hematocrit (%)
Mean corpuscular volume
Mean
Lower limit
Mean
Lower limit
Mean
Lower limit
12.5 12.5 13.0 13.5
11.0 11.0 11.5 12.0
37 38 39 40
33 34 35 36
77 79 81 83
70 73 75 76
13.5 14.0
12.0 12.5
41 43
36 37
85 84
78 77
14.0 15.0
12.0 13.0
41 46
36 38
87 86
79 78
14.0 16.0
12.0 14.0
42 47
37 40
90 90
80 80
Adapted from Hoekeleman et al., 2001.
prenatal period. In the first 6 months of life, full-term infants have sufficient iron stores, but these stores gradually are being depleted (Hoekeleman et al., 2001; Kohli-Kumar, 2001). In preterm infants, anemia may develop earlier than 12 months from insufficient iron stores (Alkalay, Galvis, Ferry, Simmons, & Krueger, 2003). Dietary intake of iron replaces the loss of stored iron from prenatal life. Preschool-aged children in low-income families, newly immigrant children, or refugee children are at high risk for iron deficiency. They should be screened at 9 to 12 months of age and 6 months later (Bogen, Duggan, Dover, & Wilson, 2000). High-risk groups of children should be screened annually from 2 years to 5 years (Graham & Uphold, 2003; Kohli-Kumar, 2001). During the school age years, only high-risk children need to be screened. Adolescent boys also do not need to be screened unless they are at risk. Adolescent girls should be screened every 5 to 10 years. Children with any other conditions that suggest the potential for anemia should have routine screening to assess for chronic 382 Volume 19 • Number 6
anemia, blood loss, or low iron intake (Graham & Uphold). Laboratory Evaluation of Anemia The American Academy of Pediatrics recommends screening all children for anemia by the 12month visit (Behrman, Kliegman, & Jenson, 2004). The normal values of hemoglobin and hematocrit vary by age (Table 1). Measurements of hemoglobin, hematocrit, and red cell indices provide information about the red cells that assists in the diagnosis of the underlying cause of anemia. Red cell indices include the mean cell volume, mean hemoglobin, mean cell hemoglobin concentration, and red blood cell distribution width (Hoekeleman et al., 2001). Serum ferritin concentration is the measurement of iron storage and contributes to the diagnosis of iron deficiency. Transferrin saturation measures dietary iron absorption and transport (Graham & Uphold, 2003). Describing cell morphology is a method of classification of anemia. Cell morphology can be determined by a peripheral film and mean corpuscular volume. The red blood cell can be described as microcytic, normocytic, or macrocytic. Understanding the description of the cell and
additional information about other red blood cell indices can assist with diagnosing the etiology of the anemia, leading to treatment options (Behrman et al., 2004; Hoekeleman et al., 2001). Microcytic Anemia Several diseases produce microcytic red blood cells, iron deficiency anemia, thalassemia trait, lead poisoning, chronic inflammation, and sideroblastic anemia. In most children who have microcytic red blood cells, there is a defect in hemoglobin synthesis (Behrman et al., 2004). Iron deficiency anemia is a frequent problem in pediatrics and is most commonly treated by nurse practitioners (Graham & Uphold, 2003). When iron is in short supply, the body decreases the production of hemoglobin. The red cells become hypochromatic and microcytic. Iron deficiency produces a chronic anemia that may have long-term psychological, motor, and behavioral functioning (Kazal, 2002; Lozoff et al., 2000). Iron deficiency also can develop in the first year of life in children who are fed low-iron formula. Young boys may be most affected by iron deficiency (Abelson, 2001; Doemellof et al., 2002). ChilJournal of Pediatric Health Care
TABLE 2. Laboratory values in microcytic anemia in children Iron deficiency
Hemoglobin Mean corpuscular value Red blood cell count Relative distribution width Hb Electrophoresis Ferritin
Thalassemia
Hemoglobin E
Low/very low Low/very low Low High
Low Very low High Normal
Low Very Low High Normal
Normal Low
Normal;  ⫽ more A2 Normal
Normal Normal
Adapted from Rudolph et al., 2002.
dren between 12 and 24 months of age are at the highest risk of any age group for iron deficiency anemia because of their rapid growth and lack of dietary sources of iron (Abelson; Doemellof et al.). Adolescence is another period of rapid growth when iron stores can be depleted because the diet does not replace the loss of iron. Adolescent girls are at greatest risk if they have heavy menstrual periods (Graham & Uphold, 2003). Lead poisoning is another cause of microcytic anemia. Lead inhibits the synthesis of hemoglobin, causing an anemia similar to iron-deficiency anemia. Lead levels are high and target cells and basophilic stripling may be present in the red cell, resulting in anemia (Centers for Disease Control and Prevention, 1997). Normocytic Anemias Normocytic red cell morphology in the presence of anemia is caused by increased destruction of red blood cells or decreased production of red blood cells. The normocytic cells can be associated with a low reticulocyte count or a high reticulocyte count. Determining the reticulocyte count in normocytic anemia assists in diagnosis of selected diseases. If the cell morphology is normocytic and associated with a low reticulocyte count, the most common diseases occurring in childhood are Diamond-Blackfan anemia and transient erythroblastopenia (Crocetti, Hwit, & Kato, 2002). Other diseases that have the cell morphology of normocytic cells inJournal of Pediatric Health Care
clude panocytopenias and chronic hemolytic anemia. Children with anemia from panocytopenia will have severe anemia, low platelets, and a low white blood cell count. A white blood cell count with differential is indicated when the anemia is very severe. In panocytopenia the symptoms are acute: a sudden drop in hemoglobin, weakness, pallor, fatigue, and possibly shock. Chronic hemolytic anemia occurs in children with sickle cell disease or hereditary spherocytosis. When the red cell production decreased suddenly, these children experience an acute drop in the hematocrit, producing the symptoms of shock or an aplastic crisis (Hoekeleman et al., 2001). Anemia can occur in conjunction with chronic illness. This anemia produces a normocytic, normochromatic red cell. When red cells are destroyed, there is a corresponding increase in production of red blood cells. The anemia produced has normocytic cell morphology with an elevated reticulocyte count. Anemia conditions that produce this clinical picture are disseminating intravascular coagulation, hemolytic uremic syndrome, cardiac prosthetic devices, and autoimmune system diseases that cause hemolysis. The peripheral film reveals cell destruction, with small fragments of red cells frequents evident (Hoekeleman et al.). Normocytic cells are seen in autoimmune hemolytic anemia, but this disease is rare in children after
the newborn period of life. A child with autoimmune hemolytic anemia usually is jaundiced and has splenomegaly. A positive Coombs test is diagnostic for this problem. The child should be evaluated for an underlying systemic disorder, such as a malignancy, immune deficiencies, collagen vascular disease, drugs, Mycoplasma pneumonia, Epstein-Barr virus, and human immune deficiency virus. Prednisone often is the treatment of choice for autoimmune hemolytic anemia (Hoekeleman et al., 2001). Enzyme deficiencies in red blood cells produce a normocytic anemia with an elevated reticulocyte count. Glucose-6-phosphate dehydrogenase is the most common disease resulting from enzyme deficiencies that occurs in childhood. Normocytic cell morphology is present in anemia caused by hemoglobinopathies. Hemoglobinopathies are a group of hemolytic disorders in which there are abnormalities in the ␣ or  chain of the hemoglobin molecule (Hoekeleman et al., 2001). Macrocytic Anemias Macrocytic anemia is very rare in children. Vitamin B12, folate deficiencies, inborn errors of metabolism that inhibit folate absorption, and poor nutritional intake can cause malabsorption syndromes that produce anemia. In the peripheral blood smear, the red blood cells are macrocytic and the MCV is 100 to 140 fL. Serum levels of B12 or folate can be evaluated to determine the etiology of a macNovember/December 2005 383
rocytic anemia. Large red blood cells occur in several disease processes such as hypothyroidism. Children with Down syndrome and newborns have macrocytosis (Hoekeleman et al., 2001). MANAGEMENT OF ANEMIA The clinical guidelines for pediatric nurse practitioners address the procedures for management of iron deficiency anemia (Graham & Uphold, 2003) and suggest the indications for referral. The initial treatment depends on the etiology, the results of laboratory tests, and the clinical symptoms of the child. The most common identification of anemia is through routine screening. Additional laboratory examination should include a complete blood cell count, reticulocyte count, a peripheral smear, and a mean corpuscular volume when the hemoglobin is between 8 g/dL to 11 g/dL (Table 2). If the red blood cell is microcytic, the most common reason for the anemia is iron deficiency. Irondeficiency anemia is treated with oral iron in the dose of 2 to 6 mg/kg per day or elemental iron. Children younger than 5 years are treated with Feosol that has 44 mg of elemental iron in each 5 mL and is divided into 3 doses per day. Children from 5 to 12 years can be treated with one 60 mg tablet of elemental iron. Adolescents are treated with one to two tablets of elemental iron each day. Ferrous sulfate is the form of oral iron most easily tolerated. The hemoglobin should be re-evaluated after 1 to 2 months of treatment. The treatment should continue for 3 to 6 months after the anemia has resolved (Dershewitz, 1999; Graham & Uphold, 2003). In addition to management with supplemental iron, the child’s diet should be evaluated and dietary counseling should be provided. The family should be educated to increase the consumption of meat if the family does not prefer a vegetarian diet. Meat is the source of 384 Volume 19 • Number 6
iron that is best tolerated (Dershewitz, 1999; Graham & Uphold, 2003). Iron should be taken between meals and with vitamin C juices. Infants should be given iron preparations in the back of their mouth to avoid staining their teeth. Iron should not be taken with dairy products, antacids, calcium supplements, coffee, tea, bran, and whole grains, because these products decrease the absorption of iron. Iron preparation should be out of reach of young children because accidental poisoning can occur with ingestion of iron (Graham & Uphold). If parents are continuing to provide the recommended treatment and the anemia does not resolve, additional testing is required (Graham & Uphold). If the child’s anemia does not
hematocrit is dropping rapidly, and when anemia occurs in a child who is ill (Hoekeleman et al., 2001). Iron deficiency anemia should be prevented as well as treated. Primary prevention includes encouraging mothers to take prenatal vitamins with an iron preparation and breastfeeding for infants; the breastfeeding mother should continue to take prenatal vitamins for the first 6 months of breastfeeding (Geltman et al., 2004; Graham & Uphold, 2003). After breastfeeding is discontinued, children should receive two or more servings of iron-fortified infant cereal (Graham & Uphold). Infants on formula should have iron-supplemented formula (Baker et al., 1999).
Iron should not be taken with dairy products, antacids, calcium supplements, coffee, tea, bran, and whole grains, because these products decrease the absorption of iron. resolve after 1 month of treatment, alternative etiologies should be sought (Davis & Nowicki, 2004). Nurse practitioners should obtain a complete blood cell count with red cell indices and a peripheral smear and a hemoglobin electrophoresis. When iron stores are sufficient, these tests will help the nurse practitioner to diagnosis the thalassemias (Abelson, 2001). The practitioner should refer to a pediatric hematologist if the anemia is either very severe or initial treatment is not effective (Graham & Uphold, 2003). Other indications for referral are when the hematocrit is less than 25%, when the anemia is unexplained, and when there is pancytopenia. The child should be hospitalized when the hematocrit is less than 15% to 20%, when the
CONCLUSIONS Anemia often is caused by iron deficiency, but other causes exist as well. Pediatric nurse practitioners should be aware of the etiologies of anemia, the steps to take to diagnose anemia, and the most common causes of anemia in children. Iron-deficiency anemia should be prevented as well as treated with appropriate ongoing assessment of diet and patterns of growth. If the family has been able provide the recommended treatment and the anemia continues, additional laboratory values and assessment will provide alternative etiologies. Children with any other conditions that suggest the potential for anemia should have routine screening to assess for chronic anemia, blood loss, or low iron inJournal of Pediatric Health Care
take. The long-term consequences of chronic anemia suggest that vigilance is need for this disease in all child health care. REFERENCES Abelson, H. T. (2001). Complexities in recognizing and treating iron deficiency anemia. Journal of Pediatrics and Adolescent Medicine, 155, 332-333. Alkalay, A. L., Galvis, S., Ferry, D. A., Simmons, C. F., & Krueger, R. C. (2003). Hemodynamic changes in anemic premature infants: Are we allowing the hematocrits to fall too low. Pediatrics, 112, 838-845. Baker, S. S., Cochran, W. J., Flores, C. A., Georgieff, M. K., Jacobson, M. S., Jaksic, T., et al. (1999). Iron fortification of infant formulas. Pediatrics, 104, 119123. Behrman, R. E., Kliegman, R. M., & Jenson, H. B. (2004). Nelson textbook of pediatrics (17th ed.). Philadelphia: Saunders. Bogen, D. L., Duggan, A. K., Dover, G. J., & Wilson, M. H. (2000). Screening for iron deficiency anemia by dietary history in a high-risk population. Pediatrics, 105, 1254-1259. Carley, A. (2003). Anemia: When it is not iron deficiency? Pediatric Nursing, 29, 205211. Childs, F., Aukett, P., Darbyshire, S., Ilett, S., & Livera, N. (1997). Dietary education and iron deficiency anaemia in the inner city. Archives of Diseases in Childhood, 76, 144-147.
Crocetti, M., Hwit, F., & Kato, G., (2002). Transient erythroblastopenia of childhood: Listening for quiet anemia. Contemporary Pediatrics, 4, 79-91. Centers for Disease Control and Prevention. (1997) Screening young children for lead poisoning: Guidelines for state and local health departments. Atlanta, GA: Author. Davis, D. B., & Nowicki, M. J. (2004). A sallow infant. Clinical Pediatrics, 43, 587591. Doemellof, M., Lonnerdal, B., Dewey, K. G., Cohen, R. J., Rivera, L., & Hernell, O. (2002). Sex differences in iron status during infancy. Pediatrics, 110, 545-552. Dershewitz, R. A., ed. (1999). Ambulatory pediatric. (3rd ed.). Philadelphia: Lippincott-Raven. Geltman, P., Meyers, A., Mehta, S., Brugnara, C., Villon, I., Wu, Y., et al. (2004). Daily multivitamins with iron to prevent anemia in high-risk infants: A randomized clinical trial. Pediatrics, 114, 86-93. Graham, M. V., & Uphold, C. R. (2003). Clinical guidelines in child health (3rd ed.). Florida: Barmare Books. Hoekeleman, R. A., Adam, H. M., Nelson, N. M, Weitzman, M. L., & Wilson, M. H. (2001). Primary pediatric care (4th ed.). St. Louis, MO: Mosby. Kahn, J. L., Binns, H. J., Chen, T., Tanz, T. T., & Listernick, R. (2002). Persistence and emergence of anemia in children during participation in the special supplemental nutrition program for women, infants and children. Archives of Pediatrics and Adolescent Medicine, 156, 1028-1032.
Kazal, L. A. (2002). Prevention of iron deficiency in infants and toddlers. American Family Physician, 2266, 12171225. Kohli-Kumar, M. (2001). Screening for anemia in children: AAP recommendations—a critique. Pediatrics, 108, 1-2. Kumar, V., Cotran, R. S., & Robbins, S. L. (2003). Robbins basic pathology. Philadelphia: Saunders. Lozoff, B., Jimenez, E., Hagen, J., Mollen, E., & Wolf, A. W. (2000). Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency anemia. Pediatrics, 105, 5164. Nead, K. G., Halterman, J. S., Kaczorowski, J. M., Auinger, P., & Weitzman, M. (2004). Overweight children and adolescents: A risk group for iron deficiency. Pediatrics, 114, 104-108. Rudolph, A. M., Kamei, R. K., & Overby, D. J. (2002). Rudolph’s fundamentals of pediatrics (3rd ed.). New York: McGraw-Hill. Sherry, B., Bister, D., & Yip, R. (1997). Continuation of decline in prevalence of anemia in low-income children: The Vermont experience. Archives of Pediatrics & Adolescent Medicine, 151, 928-930. Sherry, B., Zuguao, M., & Yip, R. (2001). Continuation of the decline in prevalence of anemia in low-income infants and children in five states. Pediatrics, 107, 677-682. Wong, D. L., Hockenberry, M. J., Wilson, D., Winkelstein, M. L., & Kline, N. E. (2003). Nursing care of infants and children. St. Louis, MO: Mosby.
CALL FOR MANUSCRIPTS The Journal of Pediatric Health Care welcomes manuscripts related to pediatric clinical practice (ambulatory care, primary care, home health care, school health, inpatient care), health care policy, or role issues relevant to the pediatric nurse practicing in an expanded role. Please submit manuscripts to the Editor at the following address: Bobbie Crew Nelms, PhD, RN, CPNP 3133 Barbara St San Pedro, CA 90731 For details about the Journal’s editorial policy and manuscript preparation, see the Information for Authors pages.
Journal of Pediatric Health Care
November/December 2005 385
Anemia: Diagnosis and Management Sharon M. Coyer, PhD, APN, CPNP
ABSTRACT Anemia is a pathologic condition produced by a decrease in red blood cell mass or a decrease in the amount of hemoglobin. Anemia is a common occurrence in the United States. Children from some ethnic groups have a higher incidence of anemia, but anemia also can affect overweight children and children with chronic illnesses. Iron-deficiency anemia, which is the most common cause of anemia and can produce long-term developmental outcomes, continues to be prevalent in some groups of children. This article will review the procedures for taking a history, determining the etiology, and providing initial treatment for the anemia. J Pediatr Health Care. (2005) 19, 380-385.
Sharon M. Coyer is Assistant Professor, Northern Illinois University, School of Nursing, DeKalb, Ill. Reprint requests: Sharon M. Coyer, PhD, APN, CPNP, School of Nursing, Northern Illinois University, 1240 N Normal Rd, DeKalb, IL 60115; e-mail: [email protected] 0891-5245/$30.00 Copyright © 2005 by the National Association of Pediatric Nurse Practitioners. doi:10.1016/j.pedhc.2005.07.014
380
Volume 19 • Number 6
www.jpedhc.org
Anemia is a pathologic condition in which there is a decrease in red blood cell mass or a decrease in the amount of hemoglobin (Carley, 2003; Kumar, Cotran, & Robbins, 2003). Anemia is a common occurrence in the United States. As many as 20% of children have anemia, and ethnic groups may have a higher incidence, such as AfricanAmerican children (24.6%) and Hispanic children (18.4%) (Carley). Anemia may develop in overweight children (Nead, Halterman, Kaczorowski, Auinger, & Weitzman, 2004). Iron-deficiency anemia can produce long-term developmental outcomes and continues to be prevalent in some groups of children (Childs, Aukett, Darbyshire, Ilett, & Livera, 1997; Lozoff, Jimenez, Hagen, Mollen & Wolf, 2000). Anemia continues to occur in groups of children with an inadequate diet, although supplemental food programs have helped some parents provide their children with foods with higher iron content (Kahn, Binns, Chen, Tanz, & Listernick, 2002; Sherry, Bister, & Yip, 1997; Sherry, Zuguao, & Yip, 2001). Children living in high-altitude locations and some ethnic groups have different criteria for evaluating the normal hemoglobin (Hoekeleman, Adam, Nelson, Weitzman, & Wilson, 2001). If the child has a chronic condition, such as cystic fibrosis, the child may require a higher hemoglobin and hematocrit to avoid the problems associated with anemia. For nurse practitioners, the evaluation of the hemoglobin and hematocrit of a child requires not only evaluating the normal range for the child’s age but also whether the child’s hemoglobin and hematocrit has changed significantly since the last visit. This article will review the procedures for taking a history, determining the etiology, Journal of Pediatric Health Care
Anemia can be classified in two ways: by the physiologic process of red blood cell loss or by the size, color, and shape of the red blood cells.
and providing initial treatment for the anemia. PATHOPHYSIOLOGY OF ANEMIA Anemia can be classified in two ways: by the physiologic process of red blood cell loss or by the size, color, and shape of the red blood cells. The classification of anemia based on physiologic process includes several etiologies. Anemia can be caused by a decrease in red cells as a result of blood loss, increased rate of destruction of the red cell, and impaired red cell production. Blood loss occurs during acute or chronic diseases (Rudolph, Kamei, & Overby, 2002). Increased rate of destruction of red cells occurs in various hemolytic anemias, resulting from both intrinsic factors and extrinsic factors. Intrinsic abnormalities of red cell can be the result of hereditary or acquired diseases. Hereditary diseases have several etiologies. Sperocytosis and elliptocytosis are conditions causing anemia because of a disorder in the red cell membrane.Disorders in red cell enzymes, such as glucose-6-phosphate dehydrogenase and pyruvate synthesis diseases, also can cause anemia. Sickle cell anemia and thalassemia cause anemia because red cells have structural abnormalities (Kumar et al., 2003). There are extrinsic abnormalities of the red blood cell that produce anemia. Other extrinsic factors causing anemia are antibodymediated red cell destruction diseases, such blood transfusion reactions. Another extrinsic factor causing anemia are mechanical processes causing red cell destruction, such as hemolytic anemia, Journal of Pediatric Health Care
and thrombocytopenia purpura or disseminating intravascular coagulation. Anemia that is produced from impaired cell production occurs when there is a disturbance of proliferation and distribution of stem cells. This situation occurs in aplastic anemia, anemia from renal cell aplasia, and anemia from renal failure or endocrine disorders. Impaired cell production also can occur with a disturbance in maturation and proliferation of red
child with anemia. The nutritional history should include the mother’s dietary patterns if she is breastfeeding an infant. Infants, toddlers, and adolescent girls share the possibility of iron deficiency anemia resulting from nutrition and diet deficiencies. The review of the systems should include a newborn history of jaundice. The history should include an evaluation of extremity pain, blood loss, extensive bruising, petechia, travel, infection exposure, and drug use. A family history of jaundice, splenectomy, or cholecystectomy suggests a hereditary etiology for hemolytic anemia diseases (Dershewitz, 1999). The physical examination should include a comprehensive review of the plotted growth charts and a survey of the patterns of
The history should include an evaluation of extremity pain, blood loss, extensive bruising, petechia, travel, infection exposure, and drug use. cells. Impaired cell production occurs when cells have defective DNA synthesis such in vitamin B12 and folic acid anemia. Defective hemoglobin synthesis is the pathologic process for iron deficiency anemia, thalassemia, and the anemia of chronic infections (Kumar et al., 2003). DIAGNOSIS OF ANEMIA Family and Physical History The history provides valuable information for the diagnostic workup. A family history should include information about the ethnic heritage of the family, any history of anemias, splenectomy, jaundice, gallbladder disease, sickle cell trait, or thalassemia. A nutritional history is an important part of the history in the evaluation of a
growth of the child over a period of time to determine the potential for chronic anemia. The physical examination also should include an evaluation of the child for pallor, jaundice, petechiae, bruising, murmurs adenopathy, organomegaly, frontal bossing, and congenital anomalies (Dershewitz, 1999). The blood pressure, heart rate, and respiratory rate also should be evaluated using the appropriate normative values for the child’s age and height (Wong, Hockenberry, Wilson, Winkelstein, & Kline, 2003). Lack of iron stores at birth, low level of iron in the diet during growth, and blood loss all cause iron deficiency and can lead to iron deficiency anemia. Iron stores are developed during the November/December 2005 381
TABLE 1. Normal values for hemoglobin, hematocrit and mean corpuscular value Hemoglobin (g/dL)
Age (y) 0.5-1.9 2-4 5-7 8-11 12-14 Female Male 15-17 Female Male 18-49 Female Male
Hematocrit (%)
Mean corpuscular volume
Mean
Lower limit
Mean
Lower limit
Mean
Lower limit
12.5 12.5 13.0 13.5
11.0 11.0 11.5 12.0
37 38 39 40
33 34 35 36
77 79 81 83
70 73 75 76
13.5 14.0
12.0 12.5
41 43
36 37
85 84
78 77
14.0 15.0
12.0 13.0
41 46
36 38
87 86
79 78
14.0 16.0
12.0 14.0
42 47
37 40
90 90
80 80
Adapted from Hoekeleman et al., 2001.
prenatal period. In the first 6 months of life, full-term infants have sufficient iron stores, but these stores gradually are being depleted (Hoekeleman et al., 2001; Kohli-Kumar, 2001). In preterm infants, anemia may develop earlier than 12 months from insufficient iron stores (Alkalay, Galvis, Ferry, Simmons, & Krueger, 2003). Dietary intake of iron replaces the loss of stored iron from prenatal life. Preschool-aged children in low-income families, newly immigrant children, or refugee children are at high risk for iron deficiency. They should be screened at 9 to 12 months of age and 6 months later (Bogen, Duggan, Dover, & Wilson, 2000). High-risk groups of children should be screened annually from 2 years to 5 years (Graham & Uphold, 2003; Kohli-Kumar, 2001). During the school age years, only high-risk children need to be screened. Adolescent boys also do not need to be screened unless they are at risk. Adolescent girls should be screened every 5 to 10 years. Children with any other conditions that suggest the potential for anemia should have routine screening to assess for chronic 382 Volume 19 • Number 6
anemia, blood loss, or low iron intake (Graham & Uphold). Laboratory Evaluation of Anemia The American Academy of Pediatrics recommends screening all children for anemia by the 12month visit (Behrman, Kliegman, & Jenson, 2004). The normal values of hemoglobin and hematocrit vary by age (Table 1). Measurements of hemoglobin, hematocrit, and red cell indices provide information about the red cells that assists in the diagnosis of the underlying cause of anemia. Red cell indices include the mean cell volume, mean hemoglobin, mean cell hemoglobin concentration, and red blood cell distribution width (Hoekeleman et al., 2001). Serum ferritin concentration is the measurement of iron storage and contributes to the diagnosis of iron deficiency. Transferrin saturation measures dietary iron absorption and transport (Graham & Uphold, 2003). Describing cell morphology is a method of classification of anemia. Cell morphology can be determined by a peripheral film and mean corpuscular volume. The red blood cell can be described as microcytic, normocytic, or macrocytic. Understanding the description of the cell and
additional information about other red blood cell indices can assist with diagnosing the etiology of the anemia, leading to treatment options (Behrman et al., 2004; Hoekeleman et al., 2001). Microcytic Anemia Several diseases produce microcytic red blood cells, iron deficiency anemia, thalassemia trait, lead poisoning, chronic inflammation, and sideroblastic anemia. In most children who have microcytic red blood cells, there is a defect in hemoglobin synthesis (Behrman et al., 2004). Iron deficiency anemia is a frequent problem in pediatrics and is most commonly treated by nurse practitioners (Graham & Uphold, 2003). When iron is in short supply, the body decreases the production of hemoglobin. The red cells become hypochromatic and microcytic. Iron deficiency produces a chronic anemia that may have long-term psychological, motor, and behavioral functioning (Kazal, 2002; Lozoff et al., 2000). Iron deficiency also can develop in the first year of life in children who are fed low-iron formula. Young boys may be most affected by iron deficiency (Abelson, 2001; Doemellof et al., 2002). ChilJournal of Pediatric Health Care
TABLE 2. Laboratory values in microcytic anemia in children Iron deficiency
Hemoglobin Mean corpuscular value Red blood cell count Relative distribution width Hb Electrophoresis Ferritin
Thalassemia
Hemoglobin E
Low/very low Low/very low Low High
Low Very low High Normal
Low Very Low High Normal
Normal Low
Normal;  ⫽ more A2 Normal
Normal Normal
Adapted from Rudolph et al., 2002.
dren between 12 and 24 months of age are at the highest risk of any age group for iron deficiency anemia because of their rapid growth and lack of dietary sources of iron (Abelson; Doemellof et al.). Adolescence is another period of rapid growth when iron stores can be depleted because the diet does not replace the loss of iron. Adolescent girls are at greatest risk if they have heavy menstrual periods (Graham & Uphold, 2003). Lead poisoning is another cause of microcytic anemia. Lead inhibits the synthesis of hemoglobin, causing an anemia similar to iron-deficiency anemia. Lead levels are high and target cells and basophilic stripling may be present in the red cell, resulting in anemia (Centers for Disease Control and Prevention, 1997). Normocytic Anemias Normocytic red cell morphology in the presence of anemia is caused by increased destruction of red blood cells or decreased production of red blood cells. The normocytic cells can be associated with a low reticulocyte count or a high reticulocyte count. Determining the reticulocyte count in normocytic anemia assists in diagnosis of selected diseases. If the cell morphology is normocytic and associated with a low reticulocyte count, the most common diseases occurring in childhood are Diamond-Blackfan anemia and transient erythroblastopenia (Crocetti, Hwit, & Kato, 2002). Other diseases that have the cell morphology of normocytic cells inJournal of Pediatric Health Care
clude panocytopenias and chronic hemolytic anemia. Children with anemia from panocytopenia will have severe anemia, low platelets, and a low white blood cell count. A white blood cell count with differential is indicated when the anemia is very severe. In panocytopenia the symptoms are acute: a sudden drop in hemoglobin, weakness, pallor, fatigue, and possibly shock. Chronic hemolytic anemia occurs in children with sickle cell disease or hereditary spherocytosis. When the red cell production decreased suddenly, these children experience an acute drop in the hematocrit, producing the symptoms of shock or an aplastic crisis (Hoekeleman et al., 2001). Anemia can occur in conjunction with chronic illness. This anemia produces a normocytic, normochromatic red cell. When red cells are destroyed, there is a corresponding increase in production of red blood cells. The anemia produced has normocytic cell morphology with an elevated reticulocyte count. Anemia conditions that produce this clinical picture are disseminating intravascular coagulation, hemolytic uremic syndrome, cardiac prosthetic devices, and autoimmune system diseases that cause hemolysis. The peripheral film reveals cell destruction, with small fragments of red cells frequents evident (Hoekeleman et al.). Normocytic cells are seen in autoimmune hemolytic anemia, but this disease is rare in children after
the newborn period of life. A child with autoimmune hemolytic anemia usually is jaundiced and has splenomegaly. A positive Coombs test is diagnostic for this problem. The child should be evaluated for an underlying systemic disorder, such as a malignancy, immune deficiencies, collagen vascular disease, drugs, Mycoplasma pneumonia, Epstein-Barr virus, and human immune deficiency virus. Prednisone often is the treatment of choice for autoimmune hemolytic anemia (Hoekeleman et al., 2001). Enzyme deficiencies in red blood cells produce a normocytic anemia with an elevated reticulocyte count. Glucose-6-phosphate dehydrogenase is the most common disease resulting from enzyme deficiencies that occurs in childhood. Normocytic cell morphology is present in anemia caused by hemoglobinopathies. Hemoglobinopathies are a group of hemolytic disorders in which there are abnormalities in the ␣ or  chain of the hemoglobin molecule (Hoekeleman et al., 2001). Macrocytic Anemias Macrocytic anemia is very rare in children. Vitamin B12, folate deficiencies, inborn errors of metabolism that inhibit folate absorption, and poor nutritional intake can cause malabsorption syndromes that produce anemia. In the peripheral blood smear, the red blood cells are macrocytic and the MCV is 100 to 140 fL. Serum levels of B12 or folate can be evaluated to determine the etiology of a macNovember/December 2005 383
rocytic anemia. Large red blood cells occur in several disease processes such as hypothyroidism. Children with Down syndrome and newborns have macrocytosis (Hoekeleman et al., 2001). MANAGEMENT OF ANEMIA The clinical guidelines for pediatric nurse practitioners address the procedures for management of iron deficiency anemia (Graham & Uphold, 2003) and suggest the indications for referral. The initial treatment depends on the etiology, the results of laboratory tests, and the clinical symptoms of the child. The most common identification of anemia is through routine screening. Additional laboratory examination should include a complete blood cell count, reticulocyte count, a peripheral smear, and a mean corpuscular volume when the hemoglobin is between 8 g/dL to 11 g/dL (Table 2). If the red blood cell is microcytic, the most common reason for the anemia is iron deficiency. Irondeficiency anemia is treated with oral iron in the dose of 2 to 6 mg/kg per day or elemental iron. Children younger than 5 years are treated with Feosol that has 44 mg of elemental iron in each 5 mL and is divided into 3 doses per day. Children from 5 to 12 years can be treated with one 60 mg tablet of elemental iron. Adolescents are treated with one to two tablets of elemental iron each day. Ferrous sulfate is the form of oral iron most easily tolerated. The hemoglobin should be re-evaluated after 1 to 2 months of treatment. The treatment should continue for 3 to 6 months after the anemia has resolved (Dershewitz, 1999; Graham & Uphold, 2003). In addition to management with supplemental iron, the child’s diet should be evaluated and dietary counseling should be provided. The family should be educated to increase the consumption of meat if the family does not prefer a vegetarian diet. Meat is the source of 384 Volume 19 • Number 6
iron that is best tolerated (Dershewitz, 1999; Graham & Uphold, 2003). Iron should be taken between meals and with vitamin C juices. Infants should be given iron preparations in the back of their mouth to avoid staining their teeth. Iron should not be taken with dairy products, antacids, calcium supplements, coffee, tea, bran, and whole grains, because these products decrease the absorption of iron. Iron preparation should be out of reach of young children because accidental poisoning can occur with ingestion of iron (Graham & Uphold). If parents are continuing to provide the recommended treatment and the anemia does not resolve, additional testing is required (Graham & Uphold). If the child’s anemia does not
hematocrit is dropping rapidly, and when anemia occurs in a child who is ill (Hoekeleman et al., 2001). Iron deficiency anemia should be prevented as well as treated. Primary prevention includes encouraging mothers to take prenatal vitamins with an iron preparation and breastfeeding for infants; the breastfeeding mother should continue to take prenatal vitamins for the first 6 months of breastfeeding (Geltman et al., 2004; Graham & Uphold, 2003). After breastfeeding is discontinued, children should receive two or more servings of iron-fortified infant cereal (Graham & Uphold). Infants on formula should have iron-supplemented formula (Baker et al., 1999).
Iron should not be taken with dairy products, antacids, calcium supplements, coffee, tea, bran, and whole grains, because these products decrease the absorption of iron. resolve after 1 month of treatment, alternative etiologies should be sought (Davis & Nowicki, 2004). Nurse practitioners should obtain a complete blood cell count with red cell indices and a peripheral smear and a hemoglobin electrophoresis. When iron stores are sufficient, these tests will help the nurse practitioner to diagnosis the thalassemias (Abelson, 2001). The practitioner should refer to a pediatric hematologist if the anemia is either very severe or initial treatment is not effective (Graham & Uphold, 2003). Other indications for referral are when the hematocrit is less than 25%, when the anemia is unexplained, and when there is pancytopenia. The child should be hospitalized when the hematocrit is less than 15% to 20%, when the
CONCLUSIONS Anemia often is caused by iron deficiency, but other causes exist as well. Pediatric nurse practitioners should be aware of the etiologies of anemia, the steps to take to diagnose anemia, and the most common causes of anemia in children. Iron-deficiency anemia should be prevented as well as treated with appropriate ongoing assessment of diet and patterns of growth. If the family has been able provide the recommended treatment and the anemia continues, additional laboratory values and assessment will provide alternative etiologies. Children with any other conditions that suggest the potential for anemia should have routine screening to assess for chronic anemia, blood loss, or low iron inJournal of Pediatric Health Care
take. The long-term consequences of chronic anemia suggest that vigilance is need for this disease in all child health care. REFERENCES Abelson, H. T. (2001). Complexities in recognizing and treating iron deficiency anemia. Journal of Pediatrics and Adolescent Medicine, 155, 332-333. Alkalay, A. L., Galvis, S., Ferry, D. A., Simmons, C. F., & Krueger, R. C. (2003). Hemodynamic changes in anemic premature infants: Are we allowing the hematocrits to fall too low. Pediatrics, 112, 838-845. Baker, S. S., Cochran, W. J., Flores, C. A., Georgieff, M. K., Jacobson, M. S., Jaksic, T., et al. (1999). Iron fortification of infant formulas. Pediatrics, 104, 119123. Behrman, R. E., Kliegman, R. M., & Jenson, H. B. (2004). Nelson textbook of pediatrics (17th ed.). Philadelphia: Saunders. Bogen, D. L., Duggan, A. K., Dover, G. J., & Wilson, M. H. (2000). Screening for iron deficiency anemia by dietary history in a high-risk population. Pediatrics, 105, 1254-1259. Carley, A. (2003). Anemia: When it is not iron deficiency? Pediatric Nursing, 29, 205211. Childs, F., Aukett, P., Darbyshire, S., Ilett, S., & Livera, N. (1997). Dietary education and iron deficiency anaemia in the inner city. Archives of Diseases in Childhood, 76, 144-147.
Crocetti, M., Hwit, F., & Kato, G., (2002). Transient erythroblastopenia of childhood: Listening for quiet anemia. Contemporary Pediatrics, 4, 79-91. Centers for Disease Control and Prevention. (1997) Screening young children for lead poisoning: Guidelines for state and local health departments. Atlanta, GA: Author. Davis, D. B., & Nowicki, M. J. (2004). A sallow infant. Clinical Pediatrics, 43, 587591. Doemellof, M., Lonnerdal, B., Dewey, K. G., Cohen, R. J., Rivera, L., & Hernell, O. (2002). Sex differences in iron status during infancy. Pediatrics, 110, 545-552. Dershewitz, R. A., ed. (1999). Ambulatory pediatric. (3rd ed.). Philadelphia: Lippincott-Raven. Geltman, P., Meyers, A., Mehta, S., Brugnara, C., Villon, I., Wu, Y., et al. (2004). Daily multivitamins with iron to prevent anemia in high-risk infants: A randomized clinical trial. Pediatrics, 114, 86-93. Graham, M. V., & Uphold, C. R. (2003). Clinical guidelines in child health (3rd ed.). Florida: Barmare Books. Hoekeleman, R. A., Adam, H. M., Nelson, N. M, Weitzman, M. L., & Wilson, M. H. (2001). Primary pediatric care (4th ed.). St. Louis, MO: Mosby. Kahn, J. L., Binns, H. J., Chen, T., Tanz, T. T., & Listernick, R. (2002). Persistence and emergence of anemia in children during participation in the special supplemental nutrition program for women, infants and children. Archives of Pediatrics and Adolescent Medicine, 156, 1028-1032.
Kazal, L. A. (2002). Prevention of iron deficiency in infants and toddlers. American Family Physician, 2266, 12171225. Kohli-Kumar, M. (2001). Screening for anemia in children: AAP recommendations—a critique. Pediatrics, 108, 1-2. Kumar, V., Cotran, R. S., & Robbins, S. L. (2003). Robbins basic pathology. Philadelphia: Saunders. Lozoff, B., Jimenez, E., Hagen, J., Mollen, E., & Wolf, A. W. (2000). Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency anemia. Pediatrics, 105, 5164. Nead, K. G., Halterman, J. S., Kaczorowski, J. M., Auinger, P., & Weitzman, M. (2004). Overweight children and adolescents: A risk group for iron deficiency. Pediatrics, 114, 104-108. Rudolph, A. M., Kamei, R. K., & Overby, D. J. (2002). Rudolph’s fundamentals of pediatrics (3rd ed.). New York: McGraw-Hill. Sherry, B., Bister, D., & Yip, R. (1997). Continuation of decline in prevalence of anemia in low-income children: The Vermont experience. Archives of Pediatrics & Adolescent Medicine, 151, 928-930. Sherry, B., Zuguao, M., & Yip, R. (2001). Continuation of the decline in prevalence of anemia in low-income infants and children in five states. Pediatrics, 107, 677-682. Wong, D. L., Hockenberry, M. J., Wilson, D., Winkelstein, M. L., & Kline, N. E. (2003). Nursing care of infants and children. St. Louis, MO: Mosby.
CALL FOR MANUSCRIPTS The Journal of Pediatric Health Care welcomes manuscripts related to pediatric clinical practice (ambulatory care, primary care, home health care, school health, inpatient care), health care policy, or role issues relevant to the pediatric nurse practicing in an expanded role. Please submit manuscripts to the Editor at the following address: Bobbie Crew Nelms, PhD, RN, CPNP 3133 Barbara St San Pedro, CA 90731 For details about the Journal’s editorial policy and manuscript preparation, see the Information for Authors pages.
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