The Child with Hematologic or Immunologic Dysfunction

Red Blood Cells (Erythrocytes)

The erythrocyte is formed from the hemocytoblast in the red bone marrow. As illustrated in Fig. 35-1, the pluripotential stem cell forms the proerythroblast. The initial cell of this series has a deep blue–staining (basophilic) cytoplasm and therefore is called a basophilic erythroblast. The chief change in the erythroblast is accumulation of hemoglobin in the cytoplasm. As the basophilic material decreases and the amount of hemoglobin increases, the cell comes to be called a polychromatic erythroblast, which describes its mixture of staining properties. At the same time that the nucleus decreases in size, the basophilic material disappears, so that the cell is uniformly stained by eosin dye—hence the name orthochromatic erythroblast, or normoblast. Finally, the normoblast completely loses its nucleus by a process of extrusion as it squeezes through the pores of the membrane into the capillary. Because of the loss of its nucleus, the cell caves in on both sides, which gives the mature erythrocyte its characteristic appearance as a biconcave disk. During each of these stages the different cells continue to undergo mitosis so that increasingly greater numbers of cells are produced. Because the mature RBC does not have a nucleus, it is unable to multiply.

The reticulocyte is the last stage of development before the mature erythrocyte. Reticulocytes are slightly larger than erythrocytes, and their presence indicates active RBC production (erythropoiesis). Ordinarily the total proportion of circulating reticulocytes is between 0.5% and 1.5%. The reticulocyte, or “retic,” count is a simple laboratory test frequently used to indirectly analyze hematopoiesis.

Hemoglobin

Hemoglobin is a complex molecule composed of four globin chains. The type of hemoglobin in the cells depends on both the stage of life and the presence of any abnormalities in the genes that regulate the production of hemoglobin. Fetal hemoglobin, composed of two α and two γ chains, has a greater affinity for oxygen and is best suited to the fetal environment. During the latter part of pregnancy, the fetus begins developing adult hemoglobin (two α and two β chains). When a defect in hemoglobin synthesis is present (e.g., sickle cell disease [SCD] or thalassemia), fetal hemoglobin may be produced into adulthood. Research is currently underway to develop cell-free hemoglobin that can be used for oxygen and carbon dioxide transport. Hemoglobin values vary according to the child’s age. (See Appendix C.)

Several tests offer important information about hemoglobin. The hematocrit, which is approximately three times the concentration of hemoglobin (in grams per deciliter), indicates the percentage volume of circulating packed RBCs in the total blood. Under normal conditions, hemoglobin and the hematocrit are in a fixed relationship with each other and vary according to the child’s age and sex (Glader, 2007a; Richardson, 2007).

RBC indices are based on ratios of packed RBC volume, hemoglobin concentration, and RBC count, and they are a useful way of designating different types of anemias. Values for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) do not stay constant during infancy and childhood (Glader, 2007b; Richardson, 2007). MCH concentration (MCHC) values, however, are more constant.

MCV is the average (mean) volume or size of a single RBC. The normal range for RBCs is given in Table 35-1.

MCH is the average weight of hemoglobin in each RBC (see Table 35-1). Normochromic cells are those with a normal hemoglobin content or normal MCH. Cells with below-normal MCH are termed hypochromic, and those with above-normal MCH are termed hyperchromic (McKenzie, 2004).

MCHC is the average concentration of hemoglobin in the RBC. MCHC is calculated from the amount of hemoglobin in 100 ml of RBCs rather than the amount of hemoglobin in whole blood. The normal MCHC value of 33 g/dl is reached at 6 months of age (Pesce, 2007).

Fig. 35-2 shows how RBC indices are used as indicators of different types of anemia.

White Blood Cells (Leukocytes)

The term leukocyte encompasses a number of cells with similar yet distinct functions. They are divided into two major classes—granulocytes and agranulocytes—based on the presence or absence, respectively, of granules within the cytoplasm of the cells.

Platelets

Platelets are actually small fragments of megakaryocytes. They are smaller than blood cells, do not possess a cellular structure, and consist of a clear substance containing granules. Platelets originate from part of the myelogenous group of WBCs (see Fig. 35-1). Platelets are formed when the megakaryocytic membrane invaginates, fuses within the cell to separate the cytoplasm, and then fragments.

Classification

The anemias can be classified using two basic approaches: (1) etiology as manifested by erythrocyte or hemoglobin depletion; and (2) morphology, the characteristic changes in RBC size, shape, and color (Box 35-1).

Although the morphologic classification is useful in the laboratory evaluation of anemia, the etiology provides direction for planning nursing care. For example, anemia with reduced hemoglobin concentration may be caused by a dietary depletion of iron, and the principal intervention is replenishing iron stores.

The main causes of anemia are (1) inadequate production of RBCs or RBC components, (2) increased destruction of RBCs, and (3) excessive loss of RBCs through hemorrhage. Each of these factors affects the amount of hemoglobin that is available to carry oxygen to the cells (see Box 35-1). Therefore the classification is based on the various conditions that can result from any of these physiologic changes.

Pathophysiology and Clinical Manifestations

The basic physiologic defect caused by anemia is a decrease in the oxygen-carrying capacity of blood and consequently a reduction in the amount of oxygen available to the cells. When the anemia has developed slowly, the child usually adapts to the declining hemoglobin level. Most children seem to have a remarkable ability to function well despite low levels of hemoglobin. Also, compensatory mechanisms such as a shift in the oxyhemoglobin dissociation curve may delay the development of any obvious signs (see p. 1193).

When the hemoglobin level falls sufficiently to produce clinical manifestations, the signs and symptoms (e.g., weakness, fatigue, and a waxy pallor in severe anemia) are due to tissue hypoxia (Box 35-2). Cyanosis, which results from an increased quantity of deoxygenated hemoglobin in arterial blood, is typically not evident. Anemia is caused by decreased levels of hemoglobin or RBCs, not inadequate oxygen saturation of existing hemoglobin.

Central nervous system manifestations include headache, dizziness, lightheadedness, irritability, slowed thought processes, decreased attention span, apathy, and depression. Growth retardation resulting from decreased cellular metabolism, and coexisting anorexia is a common finding in chronic severe anemia. It is frequently accompanied by delayed sexual maturation in the older child.

The effects of anemia on the circulatory system can be profound. A reduction in hemoglobin concentration that results in decreased oxygen-carrying capacity of the blood is associated with a compensatory increase in heart rate and cardiac output (see Box 35-2). Initially this greater cardiac output compensates for the lower oxygen-carrying capacity of the blood, since blood replenished with oxygen returns to the tissues at a faster than normal rate. The increased circulation and turbulence within the heart may produce a heart murmur. Because the cardiac workload increases during exercise, infection, or emotional stress, cardiac failure may occur.

Acute or chronic hemorrhage results in loss of plasma and all formed elements of the blood. After acute hemorrhage the body replaces plasma within 1 to 3 days, maintaining blood volume. However, this results in a low concentration of RBCs, which are gradually replaced within 3 to 4 weeks. During this period there is usually a normocytic normochromic anemia, provided that iron stores are sufficient for hemoglobin synthesis.

In chronic blood loss the actual number of RBCs may be normal because of continuous replacement. However, insufficient iron is available to form hemoglobin as quickly as it is lost. As a result, erythrocytes are usually microcytic and hypochromic.

Diagnostic Evaluation

In general, anemia may be suspected from findings on the history and physical examination, such as lack of energy, easy fatigability, and pallor. Unless the anemia is severe, however, the first clue to the disorder may be alterations in the CBC, such as decreased numbers of RBCs, and decreased hemoglobin and hematocrit levels. Although anemia is sometimes defined as a hemoglobin level below 10 or 11 g/dl, this arbitrary cutoff is inappropriate for all children, since hemoglobin levels normally vary with age. (See Appendix C.)

Various findings of the CBC are also significant, such as increased reticulocyte levels, which indicate the body’s response to an increased demand for RBCs. A peripheral smear may demonstrate significant changes in the shape of RBCs, such as sickled cells. Tests to measure the amount of hemoglobin in a single cell are helpful in determining the cause of the anemia (see Table 35-1 and p. 1412). Sometimes a bone marrow aspiration may be necessary to evaluate the body’s ability to produce normal cells. For example, in leukemia the bone marrow is hyperplastic (producing increased numbers of cells), whereas in aplastic anemia the bone marrow is hypoplastic (producing decreased numbers of cells) or aplastic (producing no cells).

Tests for hematologic function do not always reflect the immediate changes occurring in the blood. For example, in acute massive hemorrhage the hemoglobin and hematocrit values may not be reliable, since the plasma volume may not increase for several hours. Without the hemodilution caused by the reexpansion of the vascular space, the hemoglobin and hematocrit may be close to normal, and the RBC loss may not be apparent. Consequently, assessing the quantity of blood loss in a seriously ill child may be difficult. The estimated volume of blood loss must be analyzed in conjunction with the child’s total blood volume to determine the percentage of blood loss. Blood specimens obtained from central lines may more accurately reflect the patient’s status than specimens obtained from an extremity because of the vasoconstriction of the peripheral vasculature. Decreased blood pressure changes are a late sign because of the compensatory mechanisms.

Therapeutic Management

The objective of medical management is to reverse the anemia by treating the underlying cause. In nutritional anemias the specific deficiency is corrected. In blood loss from acute hemorrhage, RBC transfusion may be given. In patients with severe anemia, supportive medical care may include oxygen therapy, bed rest, and replacement of intravascular volume with intravenous (IV) fluids. In addition to these general measures, the nurse may implement more specific interventions depending on the cause. The next sections discuss these interventions.

Nursing Care Management

The physical examination yields valuable evidence regarding the severity of the anemia and some indication of its possible cause (see Fig. 35-2 and Box 35-2). In interviewing the family, the nurse stresses the following areas: (1) nutrition, especially if the child is lactose intolerant or has inadequate intake of iron; (2) past history of chronic, recurrent infection; (3) eating habits, particularly pica (consumption of nonnutritive substances such as dirt, starch, lead-based paint chips, paper); (4) bowel habits and presence of frank blood in stools or black, tarry stools as a result of chronic blood loss; and (5) familial history of hereditary diseases, such as SCD or thalassemia.

The nurse should also be aware of the importance of taking a thorough history to obtain pertinent information that may aid in identifying the cause of the anemia. For example, statements such as “The baby drinks lots of milk” or “My teenager is on a liquid or vegetarian diet” are clues to possible iron deficiency.

• Take vital signs, including blood pressure, before administering blood to establish baseline data for intratransfusion and posttransfusion comparison; 15 minutes after initiation; hourly while blood is infusing; and on completion of the transfusion.

• Check the blood type and group of the recipient against the donor’s, regardless of the blood product used.

• Administer the first 50 ml of blood or initial 20% of volume (whichever is smaller) slowly and stay with the child.

• Administer with normal saline in a piggyback setup or have normal saline available.

• Administer blood through an appropriate filter to eliminate particles in the blood and prevent the precipitation of formed elements; gently shake the container frequently.

• Use blood within 30 minutes of its arrival from the blood bank. If it is not used, return it to the blood bank; do not store it in a regular unit refrigerator.

• Infuse a unit of blood (or the specified amount) within 4 hours. If the infusion will exceed this time, divide the blood into appropriate-size quantities by the blood bank, with the unused portion refrigerated under controlled conditions.

• If a reaction of any type is suspected, take vital signs, stop the transfusion, maintain a patent IV line with normal saline and new tubing, notify the practitioner, and do not restart the transfusion until the child’s condition has been medically evaluated.

Etiology

Iron deficiency anemia can be caused by any number of factors that decrease the supply of iron, impair its absorption, increase the body’s need for iron, or affect the synthesis of hemoglobin (Box 35-3). Although the clinical manifestations and diagnostic evaluation are similar regardless of the cause, the therapeutic and nursing care management depends on the specific reason for the iron deficiency. The following discussion is limited to iron deficiency anemia resulting from inadequate iron in the diet.

At birth the full-term infant has approximately a 0.5 g supply of iron, and an average of 0.8 mg of iron must be absorbed each day during the first 15 years of life (Glader, 2007b). During the last trimester of pregnancy, iron is transferred from the mother to the fetus at the rate of 4 mg/day. Most of the iron is stored in the circulating hemoglobin of the erythrocytes, and the remainder is deposited in the liver, spleen, and bone marrow. Maternally derived iron stores are adequate for the first 5 to 6 months in the full-term infant but for only about 2 to 3 months in premature infants or infants of multiple births. If dietary sources of iron are not supplied to meet the infant’s growth demands after depletion of fetal iron stores, iron deficiency anemia results. Physiologic anemia should not be confused with iron deficiency anemia resulting from nutritional causes.

Vegetarian diets, popular among teenage girls, have been associated with nutritional deficiencies. Some infants and toddlers who have been fed inappropriate vegetarian diets have had severe protein-energy malnutrition, as well as deficiencies of iron, vitamin B₁₂, and vitamin D. Unrefined cereals contain substances that modify the absorption of minerals such as zinc, calcium, and iron. Individuals consuming strict vegetarian diets that include a large amount of unrefined cereals could be at a greater risk of rickets, vitamin B₁₂ and folate deficiency, and iron deficiency anemia (Hubbard, 2004; Renda and Fischer, 2009).

Pathophysiology

Iron is required for the production of hemoglobin. One molecule of hemoglobin consists of protein (globin) combined with four molecules of a pigmented compound (heme). Each molecule of heme contains one atom of iron. When iron stores are deficient, the production of hemoglobin is reduced. Consequently, the main effect of iron deficiency is decreased hemoglobin level and reduced oxygen-carrying capacity of the blood.

Clinical Manifestations

The clinical manifestations are directly attributable to the reduction in the amount of oxygen available to the tissues and resemble those seen in any type of anemia. Usually the signs are insidious and obscure, and the severity is directly related to the duration of the dietary deficiency.

Although infants with iron deficiency anemia tend to be underweight, many are overweight because of excessive milk ingestion (known as milk baby). These children become anemic for two reasons: (1) milk, a poor source of iron, is given almost to the exclusion of solid foods; and (2) increased fecal loss of blood occurs in 50% of iron deficient infants fed cow’s milk. This asymptomatic loss of hemoglobin causes iron deficiency (Glader, 2007b; Richardson, 2007). Although chubby, these infants are pale (sometimes porcelain-like), usually demonstrate poor muscle development, and are prone to infection.

Although the mechanism is unknown, iron deficiency anemia enhances the leakage of plasma proteins, which causes edema; retarded growth; and decreased serum concentration of the proteins albumin, gamma globulin, and transferrin (a protein that binds iron and transports it through the plasma). Other manifestations of iron deficiency include irritability, tachycardia, fatigue, glossitis, angular stomatitis, and koilonychia (concave or “spoon” fingernails). The association between iron deficiency anemia and impaired neurocognitive function (attention span, alertness, and learning) in both infants and adolescents has been well established, but the mechanism by which iron deficiency anemia impairs neurologic function is unknown (Akman, Cebecci, Okur, et al, 2004; Andrews, Ullrich, and Fleming, 2009; Glader, 2007b).

Diagnostic Evaluation

Laboratory tests that measure or describe hemoglobin, the morphologic changes in the RBC, and iron concentration are usually performed (see Table 35-1). The RBC count may be normal, borderline, or moderately reduced in the child with iron deficiency anemia. Typically the nearly normal number of erythrocytes is strikingly out of proportion to the low hemoglobin concentration. RBCs are typically small (microcytic), so that MCV is decreased (see Box 35-1). For infants 1 year of age, an MCV below 70 femtoliters (fl) is considered diagnostic. In children from 1 to 10 years of age, an MCV value of 70 fl plus the child’s age in years is a quick calculation of the lower limit of normal.

The reticulocyte count is usually normal or slightly reduced because of decreased stores of iron (see Table 35-1). However, in severe anemia, when tissue hypoxia elicits an erythropoietic response, the reticulocyte count may be elevated to 3% or 4%. The level of erythrocyte protoporphyrin, the immediate precursor of heme, becomes elevated in RBCs whenever heme synthesis is disturbed.

In terms of differential diagnosis, a stool analysis for occult blood (guaiac test) is commonly performed to confirm or rule out the possibility of chronic fecal blood loss, especially from milk intolerance or structural anomalies such as diverticulitis.

Therapeutic Management

Prevention is the primary goal and is achieved through optimum nutrition and appropriate iron supplementation. In infants, the following guidelines are recommended to prevent iron deficiency (American Academy of Pediatrics, 1999; Glader, 2007a)

Once the diagnosis of iron deficiency anemia is made, therapeutic management focuses on increasing the amount of supplemental iron the child receives. This usually occurs through dietary counseling and the administration of oral iron supplements. In formula-fed infants the most convenient and best sources of supplemental iron are iron-fortified commercial formula and iron-fortified infant cereal (Glader, 2007b; Mabry-Hernandez, 2009). Iron-fortified formula provides a relatively constant and predictable amount of iron and is not associated with an increased incidence of gastrointestinal symptoms, such as colic, diarrhea, or constipation. Infants younger than 12 months of age should not be given fresh cow’s milk to decrease the possibility of gastrointestinal blood loss from intolerance to the milk protein.

Addition of iron-rich foods to the diet may not provide sufficient supplemental quantities of the mineral. Oral supplements of ferrous iron are given because this form is more readily absorbed than ferric iron and results in higher hemoglobin levels. Ingested iron is absorbed largely from the duodenum, and absorption is facilitated by an acid environment. Children normally absorb an average of 10% to 20% of the iron in oral supplements, but during periods of iron deficiency they absorb an additional 5% to 10%. Oral iron supplementation is prescribed as 3 to 6 mg of elemental iron per kilogram per day. Lower dosages of iron are associated with fewer side effects. Ideally the daily dose of iron should be given in two or three divided doses between meals. Side effects of oral iron therapy include nausea, gastric irritation, diarrhea or constipation, and anorexia, but these occur infrequently, especially in infants. If the iron produces vomiting and diarrhea, it should be administered with meals and in gradually increasing doses.

The response to oral iron therapy is reflected in a peak increase in the reticulocyte count by the fifth to the tenth day of administration. Following the reticulocyte rise, the hemoglobin and hematocrit levels and RBC count increase. The hemoglobin level rises as much as 0.5 g/dl/24 hr; therefore a substantial increase should occur by the end of 1 month (Glader, 2007b; Richardson, 2007).

If the hemoglobin level is very low or if the level fails to rise after 1 month of oral therapy, it is important to assess whether the iron is being administered correctly. Parenteral iron administration is painful; expensive; and occasionally associated with regional lymphadenopathy, transient arthralgias, or serious allergic reaction (Andrews, Ullrich, and Fleming, 2009; Glader, 2007b). Therefore parenteral iron administration is reserved for children who have iron malabsorption or chronic hemoglobinuria. The Z-track method of intramuscular injection must be used to minimize staining of the skin, and careful observation is required because of the risk of anaphylaxis. Transfusions are indicated for the most severe anemia and in cases of serious infection, cardiac dysfunction, or surgical emergency when anesthesia is required. Packed RBCs (2 to 3 ml/kg), not whole blood, are used to minimize the chance of circulatory overload. Supplemental oxygen is administered when tissue hypoxia is severe.

Next to iron deficiency, folate deficiency is the most common micronutrient deficiency (Watkins, Whitehead, and Rosenblatt, 2009). Causes of folate deficiency include inadequate diet, overcooking of vegetables with loss of folates, and malabsorption. The deficiency is treated with adequate prepared and intake of folate-enrich foods and/or 1 mg of folate daily (Watkins, Whitehead, and Rosenblatt, 2009). As macrocytic anemias, both folate and vitamin B₁₂ deficiencies result in defective ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) synthesis (Kaferle and Strzoda, 2009).

Vitamin B₁₂ deficiency commonly develops when the gastric mucosa fails to secrete sufficient intrinsic factor, which is essential for absorption of vitamin B₁₂. Deprived of vitamin B₁₂, the bone marrow produces fewer but macrocytic RBCs. The erythrocytes are usually immature and, because of their extremely fragile cell membranes, are rapidly destroyed during circulation. Treatment initially involves the administration of 100 mcg or higher dose of vitamin B₁₂ parenteral therapy for several days, followed by injections of 500 or 1000 mcg of vitamin B₁₂ every 1 to 2 months. Researchers compared oral and parenteral vitamin B₁₂ therapy and found that they yielded comparable benefits (Bolarman, Kadikoylu, Yukselen, et al, 2003; Butler, Vidal-Alaball, Cannings-John, et al, 2006).

Nursing Care Management

A primary nursing objective is to prevent nutritional anemia through family education. Nurses need to be aware of recommendations regarding iron supplementation during infancy and appropriate sources of dietary iron. The nurse should encourage parents to limit the quantity of milk, to use iron-fortified infant formulas, and to introduce solid foods. This may be difficult when parents believe milk is best for the infant and equate the resultant weight gain with “healthiness.” Although milk is an excellent food, it is deficient in iron, vitamin C, zinc, and fluoride. Sources of each of these nutrients and the role they play in preventing deficiencies need to be discussed with the family, especially the person responsible for feeding the infant. For example, the mother may have less decision-making power regarding feeding than the grandmother who cares for the child.

Also stress that overweight is not synonymous with good health. If the infant has obvious signs of anemia, such as pallor, listlessness, frequent infections, and muscular weakness, point these out as evidence of suboptimum health. In some instances it is helpful to chart the hemoglobin or hematocrit values to visually impress on parents the change in iron levels. Often, increased blood values correspond to improved physical status and reinforce the benefit of dietary or oral iron supplementation.

Instructing parents regarding proper administration of oral iron supplements is an essential nursing responsibility. Several factors, such as stomach acidity, affect the absorption of iron (see Box 13-1).

An adequate dosage of oral iron turns the stools a tarry green or black color. The nurse advises parents of this normally expected change and inquires about its occurrence on follow-up visits. Absence of the greenish black stool may be a clue to poor compliance. If compliance is an issue, make every effort to institute strategies to improve adherence to the medication regimen, such as administering the drug once a day at the most convenient time. (See Compliance, Chapter 27.)

Oral iron supplements are available in liquid or tablet form. Liquid preparations may temporarily stain the teeth. If possible, take the medication through a straw or give it through a syringe or medicine dropper placed toward the back of the mouth. Brushing the teeth after administration of the drug lessens the discoloration.

Counseling families whose children are anemic is often a difficult and challenging task. Meal planning must be based on the family’s budget, cultural pattern, and food preferences (see Cultural Competence box). Often this requires more than a brief discussion with the mother or usual caregiver about foods high in iron (see Table 13-2). For teaching to be effective, the nurse may need to offer recipes, assist in planning a shopping list, and investigate food prices for economy. Because the physical effects of anemia are insidious, parents may not consider their child ill and consequently may view the medication and diet changes as unnecessary. Stressing the physical and behavioral improvements and what effect the improved diet will have on all family members may encourage parents to adhere to the treatment plan.

Diet education of teenagers is difficult, especially because teenage girls are particularly prone to following weight-reduction diets. Emphasizing the effect of anemia on appearance (pallor) and energy level (difficulty maintaining popular activities) may be useful. (See Table 13-2 and Mineral Disturbances, Chapter 13, for sources of iron-rich foods.)

SCA—The homozygous form of the disease (HgbSS), in which valine, an amino acid, is substituted for glutamic acid at the sixth position of the β chain.

Sickle cell C disease—A heterozygous variant of SCD (HgbSC), characterized by the presence of both HgbS and hemoglobin C (HgbC), in which lysine is substituted for glutamic acid at the sixth position of the β chain.

Sickle thalassemia disease—A combination of sickle cell trait and β-thalassemia trait. In the β⁺ (beta plus) form some normal adult hemoglobin can still be produced. In the β⁰ (beta zero) form there is no ability to produce normal adult hemoglobin.

Mode of Transmission

The gene that determines the production of HgbS is situated on an autosome. When both parents have sickle cell trait, there is a 25% chance with each pregnancy of producing an offspring with SCA. In the United States it is estimated that 1 in 12 African-Americans carries the trait; therefore the risk of two African-American parents having a child with the disease is 0.7%. Other forms of SCD occur through the union of two individuals who carry the heterozygous form of hemoglobin variants.

Basic Defect

The basic defect responsible for the sickling of erythrocytes is contained in the globin fraction of hemoglobin, which is composed of 574 amino acids. Under conditions of dehydration, acidosis, hypoxia, and temperature elevation, the relatively insoluble HgbS changes its molecular structure to form long, slender crystals. These filamentous crystals cause distortion of the cell membrane, so that the cell changes from a pliable disk to a crescent- or sickle-shaped RBC. The filamentous forms are associated with much greater viscosity than those with the normal holly leaf structure of HgbA.

In most instances the sickling response is reversible under conditions of adequate oxygenation and hydration. During this time the RBCs are indistinguishable from normal erythrocytes on peripheral examination. RBCs with HgbS can sickle and unsickle under appropriate conditions. After repeated cycles of sickling and unsickling, the RBCs become irreversibly sickled.

Although the defect is inherited, the sickling phenomenon is usually not apparent until later in infancy because of the presence of fetal hemoglobin (HgbF). HgbF is composed of two α and two γ polypeptide chains. At 32 weeks of gestation, the production of β and δ chains begins. These combine with α chains to form the major adult hemoglobins: HgbA (two α and two β chains) and HgbA₂ (two α and two δ chains). The newborn with SCD is generally asymptomatic because of the protective effect of HgbF (60% to 80%), but this rapidly decreases during the first year, so that the child is at risk for sickle cell–related complications (Heeney and Dover, 2009; Driscoll, 2007).

Pathophysiology and Clinical Manifestations

The clinical manifestations of SCA are primarily the result of (1) obstruction caused by the sickled RBCs’ adhesion to vascular endothelium accompanied by inflammatory process and (2) increased RBC destruction. The entanglement and enmeshing of rigid sickle-shaped cells block the microcirculation, causing vasoocclusion (Fig. 35-3). The resultant absence of blood flow to adjacent tissues causes local hypoxia, which leads to tissue ischemia and infarction (cellular death) (Box 35-4). The sickle cell adhesion to the vascular endothelium actually sets in motion the abnormal adhesion-inflammation–increased adhesion of the sickling cycle (Redding-Lallinger and Knoll, 2006). Most of the complications seen in SCA can be traced to this cycle and its impact on various organs of the body (Fig. 35-4).

Animation—Sickle Cell Anemia

Initially the spleen may become enlarged from congestion and engorgement with sickled cells. This repeated insult to the splenic sinuses results in infarction. The functioning cells are gradually replaced by fibrotic tissue until, by the age of 5 years, the spleen has decreased in size and has been totally replaced by a fibrous mass (functional asplenia). Without the spleen to filter bacteria and to promote the release of large numbers of phagocytic cells, these individuals are highly susceptible to infection.

The liver is also altered in form and function. Liver failure and necrosis are the result of severe impairment of hepatic blood flow from anemia and capillary obstruction. Moderate hepatomegaly is common by age 1 and usually persists throughout childhood and early adulthood. The rapid destruction of RBCs often results in the development of pigmented gallstones. Obstruction of the common bile duct by gallstones is uncommon; therefore cholecystectomy is generally not recommended for asymptomatic patients. If recurrent episodes of right upper abdominal pain occur, cholecystectomy may be indicated.

Kidney abnormalities are probably the result of the same cycle of congestion of glomerular capillaries and tubular arterioles with sickle cells and hemosiderin, tissue necrosis, and eventual scarring. The principal results of kidney ischemia are hematuria, inability to concentrate urine, enuresis, and occasionally nephrotic syndrome.

Bone changes include hyperplasia and congestion of the bone marrow, which result in osteoporosis, widening of the medullary spaces, and thinning of the cortices. As a result of the weakening of bone, especially in the lumbar and thoracic regions, skeletal deformities, particularly lordosis and kyphosis, may occur. Because of chronic hypoxia, the bone becomes susceptible to osteomyelitis, frequently from Salmonella organisms. Aseptic necrosis of the femoral head from chronic ischemia is an occasional problem.

Changes in the central nervous system are primarily vascular and result from the same cyclic reaction of occlusion, ischemia, and infarction. Stroke, or cerebrovascular accident, is a major complication that occurs in approximately 11% of children with SCD by the age of 20 years and can result in permanent paralysis or death (DeBaun and Vichinsky, 2007; Driscoll, 2007). Any number of neurologic symptoms can indicate a minor cerebral insult, such as headache, aphasia, weakness, convulsions, visual disturbances, or unilateral hemiplegia. Loss of vision is usually the result of progressive retinopathy and retinal detachment. Cognitive impairment from SCA without any overt signs of neurologic injury is known as silent cerebral infarct (Driscoll, 2007; Buchanan, DeBaun, Quinn, et al, 2004). Silent cerebral infarct occurs in 22% of children with SCA and is defined as an abnormality on magnetic resonance imaging (Driscoll, 2007; Steen, Fineberg-Buchner, Hankins, et al, 2005; Buchanan, DeBaun, Quinn, et al, 2004).

Heart problems are mainly attributable to the stress of chronic anemia, which can eventually result in decompensation and failure. Cardiomegaly is visualized on chest radiographic examination, and a systolic flow murmur is frequently present as a consequence of the anemia. An echocardiogram shows cardiomegaly, septal hypertrophy, and impaired contractility (Heeney and Dover, 2009; Lanzkowsky, 2005).

With the formation of sickled erythrocytes, mechanical fragility increases, which decreases the life span of the RBC. Hemolysis occurs both during intravascular circulation and as a result of stagnation of sickled cells in the congested spleen (see Fig. 35-3). Although the body attempts to compensate through stimulated erythropoietic activity, as evidenced by a hyperplastic bone marrow, the rate of destruction exceeds the rate of production. A normocytic normochromic anemia results. With increased hemolysis, hemosiderosis (increased storage of iron) is present in the liver, spleen, bone marrow, kidneys, and lymph nodes (see Box 35-4).

Diagnostic Evaluation

Although SCA has been reported during the neonatal period and early part of infancy, it may not be recognized until the toddler or preschool period, during a crisis precipitated by an acute upper respiratory tract or gastrointestinal infection. However, early diagnosis (before 3 months of age) facilitates initiation of appropriate interventions to minimize complications. Several specific tests detect abnormal hemoglobin in the homozygous or heterozygous form of the disease.

Case Study—Sickle Cell Anemia

Examination of a stained blood smear may reveal a few sickled RBCs. Because the erythrocyte assumes its normal discoid shape under adequate oxygenation, however, no sickled cells may be present even in the homozygous form of the disease. Whenever sickle cells are found, diagnostic test results are usually positive for SCA, not sickle cell trait.

For screening purposes the sickle turbidity test (Sickledex) is performed on anticoagulated blood, which is mixed with a special solution. Because HgbS is normally much less soluble than HgbA or HgbF (as well as other variants), when it is combined with this solution, it forms a cloudy or turbid mixture. All other forms of hemoglobin result in a clear suspension. This test is a reliable screening method that uses blood from a finger or heel stick and yields accurate results in 3 minutes. If the test result is positive, however, hemoglobin electrophoresis is necessary to distinguish between those children with the trait and those with the disease.

In hemoglobin electrophoresis, the blood is specially prepared and separated into various hemoglobins by high-voltage electrophoresis. The resulting pattern of the separated peptides as it appears on paper is referred to as fingerprinting of the protein. This test is accurate, rapid, and specific for detecting the homozygous and heterozygous forms of the disease, as well as the percentages of the various hemoglobins.

Therapeutic Management

The aims of therapy are (1) to prevent the sickling phenomenon, which is responsible for the pathologic sequelae; and (2) to treat the medical emergency of sickle cell crisis. The successful achievement of these aims depends on prompt nursing interventions and medical therapies, child and family preventive measures, and innovative treatment interventions.

Three general forms of treatment are available: supportive-symptomatic, specific, and curative. Hydroxyurea is the only effective drug approved by the U.S. Food and Drug Administration (FDA) to reduce the incidence of recurrent severe painful episodes and acute chest syndrome by increasing the concentration of HgbF and ultimately to reduce complications (DeBaun and Vichinsky, 2007; Pack-Mabien and Haynes, 2009). Recent research is investigating the use of hydroxyurea to prevent stroke (Gulbis, Haberman, DuFour, et al, 2005; Heeney and Ware, 2008). Hematopoietic stem cell transplantation (HSCT) is the only potential for cure of SCD with a high risk of neurologic complications (DeBaun and Vichinsky, 2007; Driscoll, 2007).

Medical management of a crisis is directed at supportive, symptomatic, and specific treatments. The main objectives are to provide (1) bed rest to minimize energy expenditure and to improve oxygen utilization; (2) hydration through oral and IV therapy; (3) electrolyte replacement, since hypoxia results in metabolic acidosis, which also promotes sickling; (4) analgesia for severe pain from vasoocclusion (see pp. 1432-1433); (5) blood replacement to treat anemia and to reduce the viscosity of the sickled blood; and (6) antibiotic therapy to treat any existing infection.

Administration of pneumococcal, H. influenzae type b, and meningococcal vaccines is recommended for these children because of their susceptibility to infection from functional asplenia. (See Immunizations, Chapter 12.) Oral penicillin prophylaxis is recommended by 2 months of age to reduce the chance of pneumococcal sepsis (see Evidence-Based Practice box, p. 1430). The nurse assumes an important role in helping the family comply with a medication regimen and seek medical attention immediately when the child has a fever of 38.3° C (101° F) or higher, an increase in spleen size, or severe pallor (Akinyanju, Otaigbe, and Ibidapo, 2005; Driscoll, 2007; Pack-Mabien and Haynes, 2009).

Oxygen therapy is of little therapeutic value unless the patient is hypoxic (Heeney and Dover, 2009). Oxygen administration is usually not effective in reversing sickling or reducing pain because the oxygen is not able to reach the enmeshed sickled RBCs through the clogged vessels (Chiocca, 1996; Perkins, 2001). In addition, prolonged administration of oxygen can depress bone marrow activity, which further aggravates the anemia (Khoury and Grimsley, 1995).

The use of blood transfusions is another important component of care. An RBC transfusion is used in aplastic, hyperhemolytic, and splenic sequestration crises; in stroke prevention; and before general surgery. Exchange transfusion is a successful, rapid method of reducing the number of circulating sickle cells and therefore slowing down the vicious circle of hypoxia, tissue ischemia, and injury. It is used in acute chest syndrome and after a stroke to prevent recurrence and further tissue damage. Routine transfusions to maintain the hemoglobin value between 9 and 10 g/dl in children with central nervous system disease can minimize the chances of further neurologic problems. In the event of major surgery, exchange or partial exchange transfusions may be given preoperatively to prevent anoxia and suppress the formation of new sickle cells. A simple packed RBC transfusion to raise the hemoglobin value to 10 g/dl, as well as maintenance hydration preoperatively and postoperatively, is sufficient to prevent sickling complications secondary to anesthesia (DeBaun and Vichinsky, 2007; Heeney and Dover, 2009; Vichinsky, Haberkern, Neumayr, et al, 1995). However, sickle cell patients with a higher surgical risk, which may include a history of pulmonary disease, previous acute chest syndrome, stroke, or multiple hospitalizations, should undergo exchange transfusion or multiple simple transfusions to reduce the chance of SCD complications by decreasing the level of HgbS to less than 30%.

Multiple transfusions carry the risk of transmission of viral infection, hyperviscosity, transfusion reactions, alloimmunization, and hemosiderosis (Hankins, Jeng, Harris, et al, 2005; Heeney and Dover, 2009). To reduce iron overload, chelation therapy may be started (see p. 1438). Historically, deferoxamine (Desferal), as an effective parenteral chelator, was administered at 30 to 40 mg/kg over 8 to 10 hours for 5 or 6 nights per week. Deferoxamine is now used either alone or in combination with an oral chelator. Deferasirox (approved by the FDA in 2004) and deferiprone (not been approved by the FDA, but approved in more than 40 other countries) are two new oral iron chelators used worldwide alone or in combination with deferoxamine (Cunningham, Sankaran, Nathan, et al, 2009).

The appropriate time for beginning treatment is controversial, but chelation is often initiated when the ferritin level is higher than 1000 ng/ml or after a year or more of three or four weekly transfusions. Because the ferritin level is also an acute phase reactant, it is recognized as an ineffective or inaccurate test to determine iron overload (DeBaun and Vichinsky, 2007; Olivieri, 1999). In contrast, testing of a liver biopsy specimen allows an accurate and direct measurement of iron concentration but is not without risk of hemorrhage, infection, and discomfort (Cunningham, Sankaran, Nathan, et al, 2009; Olivieri, 1999). Emerging noninvasive alternatives for liver biopsy based on the magnetic properties of iron are known as magnetic susceptometry and superconducting quantum interference devices. Both devices provide an accurate measurement of hepatic iron (Brown, Subramony, May, et al, 2009; DeBaun and Vichinsky, 2007). However, neither of these specialized devices is readily available to the majority of centers.

Children with HgbSS disease and HgbS-β⁰-thalassemia have the highest risk of stroke and should be monitored with transcranial Doppler ultrasonography (TCD) (Driscoll, 2007; Heeney and Dover, 2009). TCD is a cost-effective, noninvasive ultrasound technique that screens for stroke risk in children who have SCD. TCD is performed yearly on children with SCD from 2 to 16 years of age and measures the intracranial vascular flow within the large cerebral arteries (Bulas, 2005; DeBaun and Vichinsky, 2007; Platt, 2006). The recommended treatment for children with confirmed abnormal TCD findings is chronic transfusion therapy (DeBaun and Vichinsky, 2007; Armstrong-Wells, Grimes, Sidney, et al, 2009). Multiple transfusions carry the risk of transmission of viral infection, hyperviscosity, transfusion reactions, alloimmunization, and hemosiderosis, which must be discussed with the parents or legal guardian before the initiation of a transfusion program.

In children with recurrent life-threatening splenic sequestration, splenectomy may be a lifesaving measure. However, the spleen usually atrophies on its own through progressive fibrotic changes (functional asplenia) by 6 years of age in children with SCA. Surgical splenectomy or autosplenectomy has several benefits because the spleen is the major site of sickling, sequestration, and destruction of RBCs.

Nursing Care Management

Many nurses are involved in SCA screening programs to identify persons with the abnormal hemoglobin so that therapy can be implemented for homozygotes and genetic counseling provided for heterozygotes. The nurse should seek medical attention immediately for young children who exhibit any of the signs previously described and whose families belong to a racial or geographic group know to be at risk for SCD.

Nursing Care Plan—The Child with Sickle Cell Disease

Assessment of the child in sickle cell crisis includes all areas and systems that can be affected by circulatory obstruction, including vital signs; neurologic signs; vision; hearing; and the respiratory, gastrointestinal, renal, and musculoskeletal systems. It is also important to identify the location and intensity of pain.