Chapter 48 - Hemo and Immune.docx

UNIT 12 Health Conditions of Children Hematological or Immunological Conditions Katherine Bertoni Originating US Chapter by Marilyn J. Hockenberry OBJECTIVE S On completion of this chapter the reader will be able to: Distinguish between the various categories of anemia. Describe the prevention of...

UNIT 12 Health Conditions of Children Hematological or Immunological Conditions Katherine Bertoni Originating US Chapter by Marilyn J. Hockenberry OBJECTIVE S On completion of this chapter the reader will be able to: Distinguish between the various categories of anemia. Describe the prevention of iron-deficiency anemia and the care of the child with iron-deficiency anemia. Compare sickle cell anemia and beta thalassemia major in relation to pathophysiology and nursing care. Describe the mechanisms of inheritance and nursing care of the child with hemophilia. Distinguish between the pathophysiology and nursing care of immune thrombocytopenia (ITP) and disseminated intravascular coagulation (DIC). Relate the pathophysiology and clinical manifestations of aplastic anemia, leukemia, and lymphoma. Demonstrate an understanding of the rationale of therapies for neoplastic disease. Outline a plan of care for the child with neoplastic disease and the family. Contrast the pathophysiology and management of the immuno- deficiency disorders. Describe nursing precautions and responsibilities required during blood transfusion. Describe the types of hematopoietic stem cell transplants. HEMATOLOGICAL AND IMMUNOLOGICAL DISORDERS Several tests can be performed to assess hematological function, includ- ing additional procedures to identify the cause of the dysfunction. The following discussion is limited to a description of the complete blood cell count (CBC). The CBC is the most common and one of the more valuable tests used. Other procedures, such as those related to iron, coagulation, and immune status, are discussed throughout the chapter as appropriate. The nurse should be familiar with the significance of the findings from the CBC (Table 48.1) and be aware of normal values for all ages, which are listed in Appendix B. As with any disorder, the health history and physical examination are essential to identify hematological dysfunction, and the nurse is often the first person to suspect an issue based on information from these sources. Comments by the parent(s) regarding the child’s lack of energy, food diary of poor sources of iron, frequent infections, and bleeding that is difficult to control offer clues to the more common disorders affecting the blood. A careful physical appraisal, especially of the skin, can reveal findings (e.g., pallor, petechiae, bruising) that may indicate minor or serious hematological conditions. Nurses need to be aware of the clinical manifestations of blood diseases in order to assist in recognizing symptoms and establishing a diagnosis. RED BLOOD CELL DISORDERS Anemia The term anemia describes a condition in which the number of red blood cells (RBCs) or the hemoglobin (Hgb or Hb) concentration is reduced below normal values for gender and age. This diminishes the oxygen-carrying capacity of the blood, causing a reduction in the oxygen available to the tissues. The anemias are the most common hematological disorder of infancy and childhood and are not diseases but an indication or manifestation of an underlying pathological process. Classification. Anemias are classified in relation to (1) etiology or physiology, manifested by erythrocyte or Hgb depletion, and (2) morphology, the characteristic changes in RBC size, shape, or colour (Box 48.1). Although the morphological classification is more useful 1280 TABLE 48.1 Tests Performed as Part of the Complete Blood Cell Count Test (Average Value) RBC count (4.5 to 5.5 × 1012/L) Description and Comments Number of RBCs per 1012 cells/L of blood RBCs carry oxygen from the lungs to the rest of the body Indirectly estimates Hgb content of blood Reflects function of bone marrow Hgb determination (11.5 to 15.5 g/L) Amount of Hgb g/L of whole blood Total blood Hgb primarily dependent on number of circulating RBCs but also on amount of Hgb in each cell Hct (0.35 to 0.45) Percent volume of packed RBCs in whole blood Indirectly measures Hgb content RBC indices MCV (77 to 95 fL) MCH (25 to 33 pg) MCHC (31 to 37 g/dL) RBC volume distribution width Average or mean volume (size) of a single RBC Average or mean quantity (weight) of Hgb in a single RBC MCV and MCH depend on accurate counts of RBCs, whereas MCHC does not; thus MCHC is often more reliable All indexes depend on average cell measurements and do not show individual RBC variations (anisocytosis) Average concentration of Hgb in a single RBC Average size of RBCs Differentiates some types of anemia Reticulocyte count (0.5 to 2% of total number of RBCs) Percent reticulocytes in RBCs Index of production of mature RBCs by bone marrow Decreased count indicates depressed bone marrow function. Increased count indicates erythrogenesis in response to some stimulus. When reticulocyte count is extremely high, other forms of immature RBCs (normoblasts, even erythroblasts) may be present Indirectly estimates hypochromic anemia Usually elevated in patients with chronic hemolytic anemia WBC count (5.0 to 10.0 × 109/L) Differential WBC count Neutrophils (polys) (2.5 to 8.0 × 109/L) Bands Eosinophils (0.0 to 0.5 × 109/L) Basophils (0.02 to 0.05 × 109/L) Lymphocytes (1 to 4 × 109/L) Monocytes (0.1 to 0.7 × 109/L) Number of WBCs × 109/L of blood Increased with infection or inflammation, trauma, tissue necrosis, hemorrhage, or leukemia Decreased with viral infection, hypersplenism, bone marrow, depression Total number of WBCs less important than differential count Inspection and quantification of WBC types present in peripheral blood Values are expressed as percentages; to obtain absolute number of any type of WBC, multiply its respective percentage by total number of WBCs Primary defence in bacterial infection; capable of phagocytizing and killing bacteria Immature neutrophil Increased numbers in bacterial infection Also capable of phagocytosis and killing Named for their staining characteristics with eosin dye Increased in allergic disorders, parasitic diseases, certain neoplasms, and other diseases Named for their characteristic basophilic stippling Contain histamine, heparin, and serotonin; believed to cause increased blood flow to injured tissues while preventing excessive clotting. Can increase in cases of leukemia, during inflammatory processes, or viral infections Involved in development of antibody and delayed hypersensitivity Large phagocytic cells that are involved in early stage of inflammatory reaction Absolute neutrophil count (ANC) Percent neutrophils/bands × WBC count Indicates capability of body to handle bacterial infections Platelet count (150 to 400 × 109/L) Cellular fragments that are necessary for clotting to occur Stained peripheral blood smear Visual estimation of amount of Hgb in RBCs and overall size, shape, and structure of RBCs Various staining properties of RBC structures may be evidence of immature forms of erythrocytes Shows variation in size and shape of RBCs: microcytic, macrocytic, poikilocytic (variable shapes) ANC, Absolute neutrophil count; Hct, hematocrit; Hgb, hemoglobin; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RBC, red blood cell; WBC, white blood cell. in terms of laboratory evaluation of anemia, the etiological approach provides direction for planning nursing care. For example, anemia with reduced Hgb concentration may be caused by a dietary deple- tion of iron, and the principal intervention is replenishing iron stores. The classification of anemias is found in Figure 48.1. Consequences of Anemia. The basic physiological defect caused by anemia is a decrease in the oxygen-carrying capacity of blood and con- sequently a reduction in the amount of oxygen available to the cells. When the anemia has developed slowly, the child usually adapts to the declining Hgb level. BOX 48.1 Red Blood Cell Morphology Size (Cell Size) • Drepanocytes (sickle-shaped cells) Variation in red blood cell (RBC) sizes (anisocytosis) • Numerous other irregularly shaped cells Normocytes (normal cell size) Microcytes (smaller than normal cell size) Colour (Cell Staining Characteristics) Macrocytes (larger than normal cell size) Variation in hemoglobin concentration in the RBCs Normochromic (sufficient or normal amount of hemoglobin per RBC) Shape (Cell Shape) • Hypochromic (reduced amount of hemoglobin per RBC) Variation in RBC shapes (poikilocytosis) • Hyperchromic (increased amount of hemoglobin per RBC) Spherocytes (globular cells) Fig. 48.1 Classifications of anemias. AIHA, Autoimmune hemolytic anemia; ALL, acute lymphoid leukemia; CMV, cytomegalovirus; DIC, disseminated intravascular coagulation; G6PD, glucose-6-phosphate dehydroge- nase; ITP, immune thrombocytopenic purpura. The effects of anemia on the circulatory system can be profound. Because the viscosity of blood depends almost entirely on the concen- tration of RBCs, the resulting hemodilution of severe anemia decreases peripheral resistance, causing greater quantities of blood to return to the heart. The increased circulation and turbulence within the heart may produce a murmur. Because the cardiac workload is greatly increased, especially during exercise, infection, or emotional stress, car- diac failure may ensue. Children seem to have a remarkable ability to function well despite low levels of Hgb. Cyanosis (the result of the quantity of deoxygenated Hgb in arterial blood) is typically not evident. Growth restriction, resulting from decreased cellular metabolism and coexisting anorexia, is a common finding in chronic severe anemia and is frequently accom- panied by delayed sexual maturation in the older child. Diagnostic Evaluation. In general, anemia may be suspected on the basis of findings in the health history and physical examination, such as lack of energy, easy fatigability, and pallor; however, unless the anemia is severe, the first clue to the disorder may be alterations in the CBC, such as decreased RBCs and decreased Hgb and hematocrit (Hct) levels (Figure 48.2). Although anemia is sometimes defined as a Hgb level below 100 or 110 g/L, this arbitrary cutoff is inappropriate for all chil- dren, because Hgb levels normally vary with age and comorbid condi- tions (Table 48.1). Other tests specific to a particular type of anemia are used to deter- mine the underlying cause of anemia. These are discussed in relation to the particular disorder. Therapeutic Management. The objective of medical management is to reverse the anemia by treating the underlying cause. In nutri- tional anemias, the specific deficiency is replaced. 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. Nursing Care. The assessment of anemia includes the basic tech- niques that are applicable to any condition. The age of the infant or child provides some clues regarding the possible etiology of the anemia. For example, iron-deficiency anemia occurs more fre- quently in infants and children between 6 and 36 months of age and during the growth spurt of adolescence. Ethnic background is also significant. For example, the anemias related to abnormal Hgb levels are found in Indigenous populations, Southeast Asians, and persons of African or Mediterranean descent. These same groups may be genetically predisposed to be deficient in the enzyme lactase after the period of infancy. Affected individuals CVA (stroke) Paralysis Death Retinopathy Blindness Hemorrhage Avascular necrosis (shoulder) Hepatomegaly Gallstones Splenomegaly Splenic sequestration Autosplenectomy Hematuria Hyposthenuria (dilute urine) Avascular necrosis (hip) Abdominal pain Dactylitis (hand-foot syndrome) Priapism Pain Osteomyelitis Chronic ulcers (rare in children) Fig. 48.2 Differences between effects on circulation of normal (A) and sickled (B) red blood cells with related complications. CVA, Cerebrovascular accident. are unable to tolerate lactose in the diet, with consequent intestinal irri- tation and chronic blood loss. Special emphasis should be placed on a careful history to elicit any information that might help identify the cause of the anemia. For example, a statement such as “My child drinks lots of milk” is a frequent finding in toddlers with iron-deficiency anemia. An episode of diarrhea may have precipitated temporary lactose intolerance in a young child. Stool examination for occult (microscopic) blood (Hemoccult test) can identify chronic intestinal bleeding that results from a primary or secondary lactase deficiency. It is also important to understand the sig- nificance of various blood tests. Preparing the child and family for laboratory tests. Usually several blood tests are ordered; because they are generally done sequentially rather than at one time, the child is subjected to multiple finger or heel punctures or venipunctures. Repeated punctures can be quite trau- matic, especially to a young child. However, these invasive procedures need not be as painful with the appropriate preparation (see Blood Specimens, Chapter 44). For example, the topical application of a eutec- tic mix of lidocaine and prilocaine (EMLA) before needle punctures can significantly reduce pain (see Pain Management, Chapter 34). The nurse is responsible for preparing the child and family for the tests by doing the following: Explaining the significance of each test, particularly why the tests are not all done at one time Encouraging parents or another supportive person to be with the child during the procedure Allowing the child to play with the equipment on a doll or partic- ipate in the actual procedure (e.g., by holding the Band-Aid) Older children may appreciate the opportunity to observe the blood cells under a microscope or in photographs. This experience is espe- cially important if a serious blood disorder, such as leukemia, is suspected, because it serves as a foundation for explaining the patho- physiology of the disorder. Bone marrow aspiration is not a routine hematological test but is essential for definitive diagnosis of certain anemias such as aplastic anemia. Decreasing tissue oxygen needs. Because the basic pathological process in anemia is a decrease in oxygen-carrying capacity, an impor- tant nursing responsibility is to minimize tissue oxygen needs by con- tinual assessment of the child’s energy level. The child’s level of tolerance for activities of daily living and play needs to be assessed and adjustments made to allow as much self-care as possible without undue exertion. During periods of rest, the nurse can take vital signs and observe behaviour to establish a baseline of nonexertion energy expenditure. During periods of activity, the nurse should repeat these measurements and observations to compare them with resting values. Preventing complications. Children who are so severely anemic that they are hospitalized may require oxygen to prevent or reduce tis- sue hypoxia. Because these children are susceptible to infection, every effort should be made to prevent exposure to infectious agents. All the usual precautions need to be taken to prevent infection, such as prac- tising thorough hand hygiene, selecting an appropriate room in a non- infectious area, restricting visitors or hospital personnel with active infection, and maintaining adequate nutrition. The nurse also needs to observe for signs of infection, particularly temperature elevation and leukocytosis. However, an elevated white blood cell (WBC) count sometimes occurs in anemia without the presence of systemic or local infection. Iron-Deficiency Anemia While the rate of iron-deficiency anemia in Canada is presumed to be quite low, the current prevalence in Canadian infants and young children is unknown (Unger et al., 2019/2021). Canadian Indigenous infants and children have a prevalence of iron-deficiency anemia that is 36% in infants 4 to 18 months old to 58% in infants 9 to 14 months old. This high prevalence is in part due to poverty, which can result in food inse- curity. Diminishing access to traditional iron-rich foods and increasing access to low-iron “convenience” foods contribute to reduced iron intake and bioavailability (Unger et al., 2019/2021). Other risk factors include living with chronic illness, suboptimal intake of iron-rich foods, and pro- longed bottle feeding (Unger et al., 2019/2021). Low birth weight infants are especially at risk. Iron supplementation is recommended for low birth weight infants (less than 2.5 kg) who are predominantly breastfed (greater than 50% of intake). Infants with a birth weight of 2.0 kg to 2.5 kg, should receive an iron supplement of 1–2 mg/kg/day for the first 6 months of age. Infants with a birth weight less than 2.0 kg, should receive an iron supplement of 2–3 mg/kg/day for the first year of age. Elemental iron supplementation is not needed when the formula used is high in iron. Preterm infants are at risk because of their reduced fetal iron supply. Noninvasive monitoring for tests such as carbon dioxide and bilirubin and clustering blood samples will minimize the amount of blood being taken in preterm infants (Lemyre et al., 2015/2021). Adolescents are at risk for iron-deficiency anemia because of their rapid growth rate combined with possible poor eating habits or menses. Pathophysiology. Iron-deficiency anemia can be caused by any number of factors that decrease the supply of iron, impair its absorp- tion, increase the body’s need for iron, or affect the synthesis of Hgb. Although the clinical manifestations and diagnostic evaluations are similar regardless of the cause, the therapeutic and nursing care man- agement depends on the specific reason for the iron deficiency. The fol- lowing discussion is limited to iron-deficiency anemia resulting from inadequate iron in the diet. During the last trimester of pregnancy, iron is transferred from preg- nant person to fetus. Most of the iron is stored in the circulating erythro- cytes of the fetus, with the remainder stored in the fetal liver, spleen, and bone marrow. These iron stores are usually adequate for the first 6 months in a full-term infant but for only 2 to 3 months in preterm infants or mul- tiple births. If dietary iron is not supplied to meet the infant’s growth demands after the fetal iron stores are depleted, iron-deficiency anemia results. Delayed clamping of the umbilical cord by 1 to 3 minutes can improve iron status and reduce the risk of iron deficiency, whereas early clamping (before 30 seconds) puts the infant at risk for iron deficiency (Rothman, 2020; Unger et al., 2019). Physiological anemia should not be confused with iron-deficiency anemia resulting from nutritional causes. Although most infants with iron-deficiency anemia are under- weight, many infants are overweight because of excessive milk ingestion (known as milk babies). These children become anemic because milk is a poor source of iron and is given almost to the exclusion of solid foods. Therapeutic Management. After the diagnosis of iron-deficiency anemia is made, therapeutic management focuses on increasing the amount of supplemental iron the child receives. This is usually done through dietary counselling and the administration of oral iron supplements. In formula-fed infants, the most convenient and best sources of supplemental iron are formula containing 6.5 mg/L to 13 mg/L of iron (which is the typical concentration in standard cow’s milk–based for- mulas in Canada) for the first 9 to 12 months with the addition of iron-rich foods after 6 months of age (Unger et al., 2019/2021). Iron-fortified formula provides a relatively constant and predictable amount of iron and is not associated with an increased incidence of gastrointestinal (GI) symptoms, such as colic, diarrhea, or constipa- tion. Infants younger than 9 to 12 months of age should not be given fresh cow’s milk because it may increase the risk of GI blood loss occurring from allergy to the milk protein or from GI mucosal dam- age resulting from a lack of cytochrome iron (heme protein) (Abdullah et al., 2011). If GI bleeding is suspected, the child’s stool should be tested on at least four or five occasions to identify any inter- mittent blood loss. Dietary addition of iron-rich foods is usually inadequate as the sole treatment of iron-deficiency anemia, since the iron is poorly absorbed and thus provides insufficient supplemental quantities. If dietary sources of iron cannot replace body stores, oral iron supplements are prescribed. Ferrous iron, more readily absorbed than ferric iron, results in higher Hgb levels. Ascorbic acid (vitamin C) appears to facilitate the absorption of iron and may be given as vitamin C–enriched foods and juices with the iron preparation. If the Hgb level fails to rise after 1 month of oral therapy, it is impor- tant to assess for persistent bleeding, iron malabsorption, not taking the medication, improper iron administration, or other causes for the ane- mia. Parenteral (IV or intramuscular [IM]) iron administration is safe and effective but painful, expensive, and occasionally associated with regional lymphadenopathy, transient arthralgias, or allergic reaction (Rothman, 2020). Thus parenteral iron is reserved for children who have iron malabsorption, chronic hemoglobinuria, or intolerance to oral prep- arations. Transfusions are indicated for the most severe anemia and in cases of serious infection, cardiac dysfunction, or surgical emergency when anaesthesia is required. Packed RBCs (2 to 3 mL/kg), not whole blood, are used to minimize the chance of circulatory overload. Supple- mental oxygen is administered when tissue hypoxia is severe. Prognosis. The prognosis for a child with this condition is very good. However, there is some evidence that iron-deficiency anemia is also associated with later, possibly irreversible, cognitive impairments. Although there is support for iron deficiency with or without anemia causing these effects, it has not been established unequivocally. Some studies suggest an increased risk of seizures, strokes, breath-holding spells in children, and exacerbations of restless legs syndrome in adults (Rothman, 2020). Nursing Care. Given the potential for adverse neurodevelopmental outcomes, minimizing the incidence of iron deficiency is an important goal. It is also important to assess for iron-deficiency anemia based on the signs and symptoms described by caregivers. Once the diagnosis is made an essential nursing responsibility is instructing parents in the administration of iron. Oral iron should be given as prescribed in two divided doses between meals, when the pres- ence of free hydrochloric acid is greatest, since more iron is absorbed in the acidic environment of the upper GI tract. Citrus fruit or juice taken with the medication aids in absorption. An adequate dosage of oral iron turns the stools a tarry green colour. The nurse needs to advise parents of this normally expected change and inquire about its occurrence on follow-up visits. Absence of the green- ish black stool may be a clue to lack of administration of iron, in either schedule or dosage. If there are concerns with the ability to give the medication, changing the schedule to more convenient times may enhance the administration. Vomiting or diarrhea can occur with iron therapy. If the parents report these symptoms, the iron can be given with meals and the dosage reduced and then gradually increased until tolerated. Liquid preparations of iron may temporarily stain the teeth. If pos- sible, the medication should be taken through a straw or given through a syringe or medicine dropper placed toward the back of the mouth. Brushing the teeth after administration of the medication lessens the discoloration. If parenteral iron preparations are prescribed, iron dextran must be injected deeply into a large muscle mass using the Z-track method. The injection site is not massaged after injection, to minimize skin staining and irritation. Because no more than 1 mL should be given in one injection site, the IV route should be considered to avoid mul- tiple injections. Careful observation with IV iron administration is required because of the risk for anaphylaxis, so a test dose is recom- mended before use. Diet. A primary nursing objective is to prevent nutritional anemia through family education. Exclusively breastfed infants as well as formula-fed infants should be fed solid foods that are iron-rich, in the form of meat, meat alternatives such as fish, eggs, and legumes, or iron-fortified cereals as first foods between 6 and 12 months of age (Critch & Canadian Paediatric Society [CPS], Nutrition and Gastroenterology Committee, 2013/2018; Health Canada et al., 2015) (see Chapter 35, Selection of Solid Foods). Preterm infants fed human milk should begin iron supplements between 2 and 6 weeks of age (Unger et al., 2019/2021). A difficulty encountered in discouraging the parents from feeding milk to the exclusion of other foods is dispelling the popular myth that milk is a “perfect food.” Many parents believe that milk is best for the infant and equate the weight gain with a “healthy child” and “good par- enting.” The nurse can also stress that being overweight is not synon- ymous with good health. Diet education of teenagers can be difficult, especially because teen- age girls are prone to following weight-reduction diets. Emphasizing the effect of anemia on appearance (pallor) and energy level (difficulty maintaining popular activities) may be useful. Sickle Cell Anemia Sickle cell anemia (SCA) is one of a group of diseases collectively termed hemoglobinopathies, in which normal adult Hgb (Hgb A [HbA]) is partly or completely replaced by abnormal sickle HgbS (HbS). Sickle cell disease (SCD) includes all the hereditary disorders with clinical, hematological, and pathological features that are related to the presence of HgbS. Even though the term SCD is sometimes used to refer to SCA, this use is incorrect. Other correct terms for SCA are HgbSS disease and homozygous sickle cell disease. The following are the most common forms of SCD: SCA—the homozygous form of the disease (HgbSS or SS), in which valine, an amino acid, is substituted for glutamic acid at the sixth position of the beta chain Sickle cell–C disease—a heterozygous variant of SCD (HgbSC), including both HgbS and HgbC (SC), in which lysine is substituted for glutamic acid at the sixth position of the beta chain Sickle thalassemia disease—a combination of sickle cell trait and beta thalassemia trait (Sβ-thal). In the β+ (beta plus) form, some normal HbA can be produced. In the β0 (beta zero) form, there is no ability to produce HbA. Of the SCDs, SCA is the most common form found in Blacks, fol- lowed by sickle cell–C disease and sickle thalassemia. Numerous other sickle syndromes exist when the HbS is paired with other mutant globin. SCA is found in 1 in 396 births of Blacks and 1 in 36 000 births of Latin Americans, with lower incidences in other ethnic groups (Smith-Whitley & Kwiatkowski, 2020). The incidence of the disease varies in different geo- graphiclocations. In Canada, there areabout 2000 people livingwithsickle cell disease (Canadian Institute of Child Health, 2021). The gene that determines the production of HgbS is situated on an autosome and, when present, is always detectable and therefore dom- inant. Heterozygous persons who have both normal HgbA and abnor- mal HgbS are said to have the sickle cell trait. Persons who are homozygous have predominantly HgbS and have SCA. The inheritance pattern is essentially that of an autosomal recessive disorder. Therefore, when both parents have the sickle cell trait, there is a 25% chance with each pregnancy of producing an offspring with SCA. Among Blacks, the incidence of the sickle cell trait is about 9%. In West Africa, the inci- dence is reported to be as high as 40% among native Africans. The high incidence of the sickle cell trait in West Africans is believed to be the result of selective protection afforded trait carriers against one type of malaria. Although the defect is inherited, the sickling phenomenon is usually not apparent until later in infancy because of the presence of fetal Hgb (HgbF). As long as the child has predominantly HgbF, sickling does not occur because there is less HgbS. The newborn with SCA is generally asymptomatic because of the protective effect of HgbF (60 to 80% HgbF), but this rapidly decreases during the first year; thus the child is at risk for sickle cell–related complications (Smith-Whitley & Kwiatkowski, 2020). Pathophysiology. The clinical features of SCA are primarily the result of (1) obstruction caused by the sickled RBCs, (2) vascular Fig. 48.3 A, Normal red blood cells (RBCs) flowing freely in a blood ves- sel. The inset shows a cross-section of a normal RBC with normal hemo- globin. B, Abnormal, sickled RBCs clumping and blocking blood flow in a blood vessel. (Other cells also may play a role in this clumping process.) The inset shows a cross-section of a sickle cell with abnormal hemoglo- bin. (From National Heart, Lung, and Blood Institute. [2008]. What is sickle cell anemia?) inflammation, and (3) increased RBC destruction (Figure 48.3). The abnormal adhesion, entanglement, and enmeshing of rigid sickle-shaped cells accompanied by the inflammatory process intermittently block the microcirculation, causing vaso-occlusion (see Figure 48.2). The resultant absence of blood flow to adjacent tissues causes local hypoxia, leading to tissue ischemia and infarc- tion (cellular death). Most of the complications seen in SCA can be traced to this process and its impact on various organs of the body. The effect of sickling and infarction on organ structures occurs in the following sequence (Box 48.2): Stasis with enlargement Infarction with ischemia and repeated destruction Replacement with fibrous tissue (scarring) Clinical Manifestations. The clinical manifestations of SCA vary greatly in severity and frequency. The most acute symptoms of the disease occur during periods of exacerbation called crises. There are several types of episodic crises: vaso-occlusive, acute splenic seques- tration, aplastic, hyperhemolytic, cerebrovascular accident (CVA) (stroke), chest syndrome, and infection. The crises may occur indi- vidually or concomitantly with one or more other crises. The vaso- occlusive crisis (VOC), preferably called a “painful episode,” is char- acterized by ischemia causing mild to severe pain that may last from minutes to days. Sequestration crisis is a pooling of a large amount of blood—usually in the spleen and infrequently in the liver—that causes a decreased blood volume and ultimately shock. Aplastic cri- sis is diminished RBC production usually caused by viral infection that may result in profound anemia. Hyperhemolytic crisis is an accelerated rate of RBC destruction characterized by anemia, jaun- dice, and reticulocytosis. Another serious complication is acute chest syndrome (ACS), which is clinically similar to pneumonia. It involves the presence of a new pul- monary infiltrate and is associated with chest pain, fever, cough, tachypnea, wheezing, and hypoxia. A CVA (stroke) is a sudden and severe complication, often with no related illnesses. Sickled cells block the major blood vessels in the brain, resulting in cerebral infarction, which causes variable degrees of neuro- logical impairment. The current treatment for children with SCA who have experienced a stroke is chronic transfusion therapy. Despite reg- ular blood transfusion therapy, approximately 20% of patients will have a second stroke and 30% of this group will have a third stroke (Smith- Whitley & Kwiatkowski, 2020). Diagnostic Evaluation. Currently, British Columbia, Ontario, and the Yukon are the only provinces that offer universal newborn screen- ing programs for SCD. Manitoba offers screening to select popula- tions or by request, and in Nova Scotia and Quebec testing is required or offered universally but not yet implemented (Canadian Institute of Child Health, 2021). The screening provides early identi- fication of these children before complications develop. At birth, infants have up to 80% of HbF, which does not carry the defect. Because levels of HbS are low at birth, Hgb electrophoresis or other tests that measure Hgb concentrations are indicated. Early diagnosis (before 3 months of age) enables initiation of appropriate interven- tions to minimize complications. The family is taught to administer prophylactic antibiotics and identify early signs of infection to seek medical therapy as soon as possible. If SCA is not diagnosed in early infancy, it is likely to manifest symp- toms during the toddler and preschool years. SCA is occasionally first diag- nosed during a crisis that follows an acute respiratory tract or GI infection. There are several specific tests used to detect the presence of the abnor- mal Hgb in the heterozygous or the homozygous form of SCD. For screening purposes, the sickle-turbidity test (Sickledex) is used because it can be performed on blood from a finger or heel stick and yields accu- rate results in 3 minutes. If the test result is positive, however, Hgb electrophoresis is necessary to distinguish between children with the trait and those with the disease. Hemoglobin electrophoresis (referred to as “fingerprinting” of the protein) is a specially prepared blood test that sep- arates various hemoglobins by high voltage. The blood test is accurate, rapid, and specific for detecting the homozygous and heterozygous forms of the disease, as well as the percentages of the various types of Hgb. Therapeutic Management. The aims of therapy are to prevent the sickling phenomena, which are responsible for the pathological sequelae, and effectively treat the medical emergencies of sickle cell cri- sis. The successful achievement of these aims depends on prompt nurs- ing interventions, medical therapies, patient and family preventive measures, and use of innovative treatments. BOX 48.2 Clinical Manifestations of Sickle Cell Anemia General Sequestration Crisis Possible growth restriction Pooling of large amounts of blood Chronic anemia (hemoglobin level of 60 to 90 g/L) Hepatomegaly Possible delayed sexual maturation Splenomegaly Marked susceptibility to sepsis Circulatory collapse Vaso-Occlusive Crisis Effects of Chronic Vaso-Occlusive Phenomena Pain in area(s) of involvement Heart—Cardiomegaly, systolic murmurs Manifestations related to ischemia of involved areas Lungs—Altered pulmonary function, susceptibility to infections, pulmonary Extremities—Painful swelling of hands and feet (sickle cell dactylitis, or insufficiency hand–foot syndrome), painful joints Kidneys—Inability to concentrate urine, enuresis, progressive renal failure Abdomen—Severe pain resembling acute surgical condition Liver—Hepatomegaly, cirrhosis, intrahepatic cholestasis Cerebrum—Stroke, visual disturbances Spleen—Splenomegaly, susceptibility to infection, functional reduction in Chest—Symptoms resembling pneumonia, protracted episodes of pulmonary splenic activity progressing to autosplenectomy disease Eyes—Intraocular abnormalities with visual disturbances; sometimes progres- Liver—Obstructive jaundice, hepatic coma sive retinal detachment and blindness Kidney—Hematuria Extremities—Avascular necrosis of hip or shoulder; skeletal deformities, espe- Genitalia—Priapism (painful, constant penile erection) cially lordosis and kyphosis; chronic leg ulcers; susceptibility to osteomyelitis Central nervous system—Hemiparesis, seizures Medical management of a crisis is usually directed by an inter- professional care team that provides supportive, symptomatic, and spe- cific treatments. The main objectives are to provide (1) rest to minimize energy expenditure and oxygen use, (2) hydration through oral and IV therapy, (3) electrolyte replacement because hypoxia results in meta- bolic acidosis, which also promotes sickling, (4) analgesics for the severe pain from vaso-occlusion, (5) blood replacement to treat anemia and reduce the viscosity of the sickled blood, and (6) antibiotics to treat any existing infection. Administration of pneumococcal, meningococcal, and Haemophilus influenzae type b conjugate vaccines is recommended for these children because of their susceptibility to infection as a result of a functional asple- nia. In addition to routine immunizations, the child with SCA should receive an annual influenza vaccination, as well as hepatitis A and B vac- cination for those who receive repeat blood transfusions. Oral penicillin prophylaxis is also recommended by 2 months of age in order to reduce the chance of pneumococcal infections in children with SCA younger than 5 years (HealthLink BC, 2020; Rankine-Mullings & Owusu- Ofori, 2017). Parents and children with SCA should be instructed in the importance of taking the prophylactic penicillin twice daily and seek- ing medical attention immediately for acute illness, especially if the tem- perature exceeds 38.5°C (101.3°F), regardless of the use of prophylaxis. Rates of pneumococcal infection were found to be relatively low in chil- dren over the age of 5 years (Rankine-Mullings & Owusu-Ofori, 2017). Oxygen therapy may be administered during episodes of crisis to pro- vide comfort and to decrease the incidence of respiratory complications. Severe hypoxia must be prevented because it causes massive systemic sick- ling that can be fatal. Oxygen administration is usually not effective in reversing sickling or reducing pain because the oxygen is unable to reach the enmeshed sickled erythrocytes in clogged vessels. Patients admitted for a febrile or vaso-occlusive episode should be carefully assessed and have continuous oxygen saturation monitoring. High-flow oxygen is adminis- tered to maintain an oxygen saturation of equal to or over 95% for early detection of clinical symptoms and/or changes in oxygenation (Canadian Haemoglobinopathy Association [CHA], 2015/2018). Another important component of care is the use of blood transfu- sions. Exchange RBC transfusion (erythrocytapheresis) is the replace- ment of sickle cells with normal RBCs. Typically, short-term transfusions are used to prevent progression of acute complications such as ACS, aplastic crisis, splenic sequestration, and acute stroke, as well as to prevent surgery-related ACS. Exchange transfusion is a successful, rapid method of reducing the number of circulating sickle cells and therefore slowing down the vicious circle of hypoxia, thrombosis, tissue ischemia, and injury. However, multiple transfusions carry the risk of transmission of viral infection, hyperviscosity, transfusion reactions, alloimmunization, and iron overload. Packed RBC transfusions may be used for treatment of splenic sequestration and stroke and preoper- atively for surgical procedures in the child with SCA. Unless the child has heart failure, dyspnea, hypotension, or marked fatigue, a blood transfu- sion is avoided unless the hemoglobin has decreased to less than 50 to 60 g/L (CHA, 2015/2018). The child with SCA should be transfused with phenotypically matched RBCs to reduce the risk of alloimmuniza- tion and hemolytic transfusion reactions (CHA, 2015/2018). To reduce iron overload from chronic transfusion therapy, chelation therapy may be started (see Chapter 46, Chelation Therapy). 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. Prophylactic penicillin postsplenectomy and pneumococcal vaccines have decreased the inci- dence of pneumococcal sepsis. The most common and debilitating symptom experienced by patients with SCA is vaso-occlusive pain. The chronic nature of this pain can greatly affect the child’s development. An interprofessional approach is best for vaso-occlusive pain management, which includes pharmacological treatment, hydration, physiotherapy, and comple- mentary treatment (e.g., prayer, spiritual healing, massage, heat, herbs, relaxation, acupuncture, and biofeedback) (Brandow et al., 2011). See Chapter 34 for more information on pain control. For mild to moderate pain, nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, ketorolac) or acetaminophen (Tylenol) is used initially. If these medications are not effective alone, opioids can be added. The dosages of both medications are titrated (adjusted) to a therapeutic level. Opioids such as immediate- and sustained-release morphine, oxy- codone, hydromorphone (Dilaudid), and methadone are administered intravenously or orally for severe pain and given around the clock. Patient-controlled analgesia (PCA) has been used successfully for sickle cell–related pain. PCA reinforces the patient’s role and responsibility in managing the pain and provides flexibility in dealing with pain, which may vary in severity over time (see Pain in Children with Sickle Cell Disease, Chapter 34). Opioid dependency in children with SCD is rare and should never be used as a reason to withhold pain medication. However, patients with multiple painful episodes requiring hospitaliza- tion within 1 year or with pain episodes that require hospitalization for greater than 7 days should be evaluated for comorbidities and environ- mental stressors that are contributing to the frequency or duration of pain (Smith-Whitley & Kwiatkowski, 2020). Hydroxyurea is a medication that increases the production of HgbF—fetal Hgb that decreases endothelial adhesion of sickle cells, improves the sickle cell hydration, increases nitric oxide production (a vasodilator), and reduces leukocyte and reticulocyte counts (Smith-Whitley & Kwiatkowski, 2020). Hydroxyurea is a Health Can- ada Food and Drug Act–approved medication. Long-term follow-up of patients taking hydroxyurea alone revealed a 40% reduction in mortal- ity and decreased frequency of VOC, ACS, hospital admissions, and need for transfusions, thus making SCA crises milder (CHA, 2015/ 2018; SickKids, 2021; Smith-Whitley & Kwiatkowski, 2020). Prognosis. The prognosis varies, but most patients with SCA live into the fifth decade. Most of the time, children are without symptoms and participate in normal activities without restrictions, but they may become fatigued more quickly than their counterparts. The greatest risk is usually in children younger than 5 years of age, and the majority of deaths in these children are caused by overwhelming infection. Conse- quently, SCA is a chronic illness with a potentially terminal outcome. Physical and sexual maturation are delayed in adolescents with SCA. Although adults achieve normal height, weight, and sexual function, the delay may present challenges for the adolescent. HLA-typing and storage of umbilical cord blood may be considered for siblings of children with SCA. HLA typing may be coordinated with prenatal diagnostic techniques (such as chorionic villus sampling, amniocentesis, or preimplantation genetic diagnosis) to determine if the fetus is affected with SCA (CHA, 2015/2018). Hematopoietic stem cell transplantation (HSCT) offers the only cure for some children. Transplants are from a sibling or unrelated donor. Sibling-matched stem cell transplantation has a lower risk for graft-versus-host disease than unrelated donors. Younger children may have lower morbidity and mortality from HSCT (Smith- Whitley & Kwiatkowski, 2020). Nursing Care Educating the family and child. Family education begins with an explanation of the disease and its consequences. After this explanation, the most important issues to teach the family are to (1) seek early inter- vention for conditions such as fever of 38.0°C (100.4°F) oral or greater, (2) give penicillin as ordered, (3) recognize signs and symptoms of splenic sequestration and respiratory difficulties that can lead to hyp- oxia, and (4) provide the same childhood experiences offered to any other child who is without illness or disease. The nurse needs to convey to the family that the child is a person like any other child but can get sick in ways that other children cannot. The nurse should emphasize the importance of adequate hydration to prevent sickling and to delay the adhesion–stasis– thrombosis–ischemia cycle in a crisis. It is not sufficient to advise par- ents to “force fluids” or “encourage drinking.” They need specific instructions on how many daily glasses or bottles of fluid are required. Many foods are also a source of fluid, particularly soups, flavoured ice pops, ice cream, sherbet, gelatin, and puddings. Increased fluids combined with impaired kidney function can result in enuresis. Parents who are unaware of this fact frequently use the usual measures to discourage bed-wetting, such as limiting fluids at night, and may resort to punishment and shame to force bladder control. The nurse should discuss this issue with the parents, stressing that the child’s ability to concentrate urine is impaired. Reminding the child to urinate fre- quently during the day and prior to bedtime may be helpful, and waking the child during the night may help if the child’s sleep pattern is not dis- turbed. Enuresis is treated as a complication of the disease, such as joint pain or some other symptom, to alleviate parental pressure on the child. Promoting supportive therapies during crises. Management of pain is an especially difficult challenge and often involves experiment- ing with various analgesics, including opioids, and schedules before relief is achieved. Unfortunately, these children tend to be undermedi- cated, resulting in “clock watching” and demands for additional doses sooner than might be expected. Often this incorrectly raises suspicions of drug addiction, when in fact the issue is one of improper dosage (see Family-Centred Care box: Fear of Addiction). In choosing and sched- uling analgesics, the goal should be prevention of pain. See Chapter 34, Pain in Children with Sickle Cell Disease. Fear of Addiction Any pain program should be combined with psychological support to help the child manage the depression, anxiety, and fear that may accompany the disease. This includes regular visits with the child to dis- cuss any concerns during the hospitalization and positive reinforcement of coping skills, such as successful methods of dealing with pain and adherence to treatment prescriptions. To reduce the negative connota- tion associated with the term sickle cell crisis, it is best to say pain episode. Frequently, heat to the affected area is soothing. Cold compresses should not be applied because this enhances sickling and vasoconstric- tion. Bed rest is usually well tolerated during a crisis, although actual rest depends greatly on pain alleviation and organized schedules of nursing care. Some activity, particularly passive range-of-motion exer- cises, is beneficial to promote circulation. Usually the best course of action is to let children dictate their tolerance of activity. If blood transfusions or exchange transfusions are given, the nurse has the responsibility of observing for signs of transfusion reaction (see Table 48.3, later in the chapter). Because hypervolemia from too-rapid transfusion can increase the workload of the heart, the nurse also needs to be alert to signs of cardiac failure. In splenic sequestration the size of the spleen is gently measured by abdominal palpation (see Abdomen, Chapter 33). The nurse should be aware of spleen size because increasing splenomegaly is an ominous sign. A decreasing spleen size denotes response to therapy. Vital signs and blood pressure are also closely monitored for impending shock. Anemia is typically not a presenting complication in VOC, but it is a critical concern in other types of crises. The nurse needs to monitor for evidence of increasing anemia and institute appropriate nursing interventions (see earlier in this chapter). Oxygen saturation level needs to be monitored carefully, and high-flow oxygen is to given if the oxy- gen saturation level drops below 95% (CHA, 2015/2018). Intake, especially of IV fluids, and output need to be recorded. The child’s weight should be taken on admission to serve as a baseline for evaluating hydration. Because diuresis can result in electrolyte loss, the nurse also should observe for signs of hypokalemia and be familiar with normal serum electrolyte values to report changes. Recognizing other complications. Nurses also need to be aware of the signs of ACS and CVA, both potentially fatal complications. It is essential to educate parents about these symptoms. Supporting the family. Families need the opportunity to discuss their feelings about genetically transmitting a potentially fatal, chronic illness to their child. Because of the widely publicized prognosis for children with SCA, many parents express their prevalent fear of the child’s death. Three manifestations of SCA that may appear in the first 2 years of life—dactylitis or painful episode, severe anemia (less than 70 g/L), and elevated WBC count—can be predictors of disease severity (Smith-Whitley & Kwiatkowski, 2020). However, nursing care for the family should be the same as for any family with a child with a life-threatening illness. The sib- lings’ reactions, the stress on the parent’s relationship, and the child-rearing attitudes displayed toward the child should be given particular emphasis (see Chapter 41). The nurse needs to advise parents to inform all treating personnel of the child’s condition. The use of medical identification, such as a brace- let, is another way of ensuring awareness of the disease. If family members have the SCD trait or SCA, genetic counselling is necessary. A primary consideration in genetic counselling is informing parents of the 25% chance with each pregnancy of having a child with the disease when both parents carry the trait. Beta Thalassemia (Cooley Anemia) Worldwide, thalassemia is a common genetic disorder with an esti- mate of approximately 60 000 symptomatic individuals born annu- ally (Hassan et al., 2016). The term thalassemia, derived from the Greek word thalassa, meaning “sea,” is applied to a variety of inher- ited blood disorders characterized by deficiencies in the rate of pro- duction of specific globin chains in Hgb. The name appropriately refers to people living near the Mediterranean Sea, namely Italians, Greeks, Syrians, Asians, Africans, and their descendants. Evidence suggests that the high incidence of the disorders among these groups is a result of the selective advantage the trait confers in relation to malaria, as is postulated in SCA. However, the disorder has a wide geographic distribution, probably as a result of genetic migration through population migration, intermarriage, or possibly as a result of spontaneous mutation. Beta thalassemia is the most common of the thalassemias and occurs in four forms: Two heterozygous forms: thalassemia minor, an asymptomatic silent carrier; and thalassemia trait, which produces a mild micro- cytic anemia Thalassemia intermedia, which may involve either homozygous or heterozygous abnormalities and is manifested as splenomegaly and moderate to severe anemia A homozygous form, thalassemia major (also known as Cooley ane- mia), which results in a severe anemia that would lead to hepato- splenomegaly, growth restrictions, bone deformities, cardiac failure, and death in early childhood without transfusion support. Pathophysiology. Normal postnatal Hgb is composed of two alpha- and two beta-polypeptide chains. In beta thalassemia there is a partial or complete deficiency in the synthesis of the beta chain of the Hgb molecule. Consequently, there is a compensatory increase in the syn- thesis of alpha chains, and gamma-chain production remains acti- vated, resulting in defective Hgb formation. This unbalanced polypeptide unit is very unstable; when it disintegrates, it damages RBCs, causing severe anemia. To compensate for the hemolytic process, an overabundance of erythrocytes is formed unless the bone marrow is suppressed by trans- fusion therapy. Excess iron from hemolysis of supplemental RBCs in transfusions and from the rapid destruction of defective cells is stored in various organs (hemosiderosis). Diagnostic Evaluation. The onset of thalassemia major may be insidious and not recognized until the latter half of infancy. The clinical effects of thalassemia major are primarily attributable to (1) defective synthesis of HgbA, (2) structurally impaired RBCs, and (3) the shortened lifespan of erythrocytes (Box 48.3). Hematological studies reveal the characteristic changes in RBCs (i.e., microcytosis, hypochromia, anisocytosis, poikilocytosis, target cells, and basophilic stippling of various stages). Low Hgb and Hct levels are seen in severe anemia, although they are typically lower than the reduction in RBC count because of the proliferation of immature BOX 48.3 Clinical Manifestations of Beta Thalassemia Anemia (Before Diagnosis) Other Features Pallor Small stature Unexplained fever Delayed sexual maturation Poor feeding Bronzed, freckled complexion (if not receiving chelation therapy) Enlarged spleen or liver Bone Changes (Older Children if Untreated) Progressive Anemia Enlarged head Signs of chronic hypoxia Prominent frontal and parietal bosses Headache Prominent malar eminences Precordial and bone pain Flat or depressed bridge of the nose Decreased exercise tolerance Enlarged maxilla Listlessness Protrusion of the lip and upper central incisors and eventual malocclusion Anorexia Generalized osteoporosis erythrocytes. Hgb electrophoresis confirms the diagnosis and is helpful in distinguishing the type of thalassemia because it analyzes the quan- tity and kind of hemoglobin variants found in the blood. Radiographs of involved bones reveal characteristic findings. Newborn screening is available to detect several thalassemia syn- dromes in Ontario, Quebec, British Columbia, Nova Scotia, New Brunswick, Yukon, and Nunavut. With an increase in immigration to Canada, testing should be offered to all new patients with a clinical suspicion of thalassemia (CHA, 2018). Therapeutic Management. The objective of supportive therapy is to maintain sufficient Hgb levels to prevent bone marrow expansion and the resulting bony deformities and to provide sufficient RBCs to sup- port normal growth and normal physical activity. Transfusions are the foundation of medical management with the goal of maintaining the Hgb level at 90–100 g/L, an aim that may require transfusions as often as every 3 to 5 weeks (CHA, 2018; Tubman et al., 2015). The advantages of this therapy include (1) improved physical and psychological well- being because of the ability to participate in normal activities, (2) decreased cardiomegaly and hepatosplenomegaly, (3) fewer bone changes, (4) normal or near-normal growth and development until puberty, and (5) fewer infections. Folic acid supplements may also be given to assist the body in producing red blood cells. One of the potential complications of frequent blood transfusions is iron overload (hemosiderosis). Because the body has no effective means of eliminating the excess iron, the mineral is deposited in body tissues. To minimize the development of hemosiderosis, the oral iron chelators deferasirox (Exjade) or deferiprone (Ferriprox) have been shown to be equivalent to deferoxamine (Desferal), a parenteral iron-chelating agent, and more tolerable by patients and families (CHA, 2018). The most commonly reported combination regimen utilizes oral defer- iprone with parenteral deferoxamine. Deferoxamine is given intrave- nously or subcutaneously at home via a portable infusion pump over a period of 8 to 10 hours (usually during sleep) for 5 to 7 days a week. In some children with severe splenomegaly who required repeated transfusions, a splenectomy may be necessary to decrease the disabling effects of abdominal pressure and to increase the lifespan of supple- mental RBCs. Over time, the spleen may accelerate the rate of RBC destruction and thus increase transfusion requirements. After a sple- nectomy, children generally require fewer transfusions, although the basic defect in Hgb synthesis remains unaffected. A major postsplenect- omy complication is severe and overwhelming infection. Therefore, these children continue to receive prophylactic antibiotics with close medical supervision for many years and should receive the influenza, pneumococcal, and meningococcal vaccines in addition to the regularly scheduled immunizations. Hepatitis A and B vaccinations are also recommended for those who receive repeat blood transfusions. Prognosis. Most children treated with blood transfusion and early chelation therapy survive well into adulthood. The most common cause of death is iron-induced heart disease, multiple-organ failure, postsplenectomy sepsis, liver disease, and malignancy. A curative treatment for some children is HSCT. Children with the least symp- toms who are younger than 14 years of age have the best results when undergoing HSCT, with an overall survival rate of 96% and a disease- free survival rate of 86% (CHA, 2018). Nursing Care. The objectives of nursing care are to (1) promote adherence to transfusion and chelation therapy, (2) assist the child and family in coping with the anxiety-provoking treatments and the effects of the illness, (3) foster the child’s and family’s adjustment to living with a chronic illness, and (4) observe for complications of multiple blood transfusions. Basic to each of these goals is explain- ing to parents and older children or adolescents the defect respon- sible for the disorder, its effect on RBCs, and the potential effects of untreated iron overload (such as diabetes and heart disease). Because the prevalence of this condition is high among families of Mediterranean descent, the nurse also needs to inquire about the family’s previous knowledge about thalassemia. All families with a child with thalassemia should be tested for the trait and referred for genetic counselling. As with any chronic illness, the family’s needs must be met for opti- mal adjustment to the stresses imposed by the disorder (see Chapter 41). Sources of information for the family are included in the Additional Resources at the end of this chapter. Genetic counselling for the parents and fertile offspring is important. If both parents are known to be carriers of beta thalassemia trait, chorionic villus sampling can be done during the first trimester (11 weeks) or by amniocentesis during the second trimester (16 weeks) (see Chapter 13). Aplastic Anemia Aplastic anemia (AA) refers to a bone marrow failure condition in which the formed elements of the blood are simultaneously depressed. BOX 48.4 Common Causes of Acquired Aplastic Anemia Human parvovirus infection, hepatitis, Epstein-Barr virus, HIV, cytomegalo- • Industrial and household chemicals, including benzene and its derivatives, virus, or overwhelming infection which are found in petroleum products, dyes, paint remov