HEMOGLOBINOPATHIES Hemoglobinopathy is a condition in which abnormal hemoglobin is present. A large percentage of the newborn’s hemoglobin is fetal hemoglobin (Hgb F). Hgb F can exchange oxygen molecules at lower oxygen tensions compared to adult hemoglobin. Over the first several months of life, Hgb F levels fall as it is replaced with Hgb A (adult hemoglobin). The healthy older infant then displays
Hgb AA. In hemoglobinopathies, this normal hemoglobin configuration
is disturbed.
Causes of hemoglobinopathies are genetic and include : sickle cell
disease (SCD), hemoglobin SC disease, α-thalassemia, and
β-thalassemia.
Sickle Cell Disease
SCD is a group of inherited hemoglobinopathies in which the RBCs do not carry the normal adult hemoglobin, but instead carry a less effective type.
SCD is most common in individuals of African, Mediterranean, Middle
1 Eastern, and Indian decent .
The focus of this discussion will be on hemoglobin SS disease. Instead of
Hgb AA, individuals with SCA have Hgb SS (Hgb A refers to adult hemoglobin,HgB S refers to sickle hemoglobin). In hemoglobin S, glutamic acid is replaced with valine in the hemoglobin molecule. This results in an elongated RBC with a
shortened lifespan. The elongated cell is more rigid than a normal cell and becomes sickled in shape .
Persons with heterozygous representation (Hgb AS) are said to have
sickle cell trait and are carriers for the disorder.
SCA is transmitted via an autosomal recessive inheritance pattern.
Infants with SCA are usually asymptomatic until 3 to 4 months of age
because Hgb F protects against sickling.
Complications of SCA include : recurrent vaso-occlusive pain crises,
stroke, sepsis, ACS, splenic sequestration, reduced visual acuity related to decreased retinal blood flow, chronic leg ulcers, cholestasis and gallstones, delayed growth and development, delayed puberty, and priapism (the sickled cells prevent blood
from flowing out of an erect penis). Children with SCA have an
increased incidence of enuresis because the kidneys cannot concentrate urine effectively.
As children reach adulthood, multiple organ dysfunction is common.
2 Pathophysiology
Significant anemia may occur when the RBCs sickle. Sickling may be triggered by any stress or traumatic event, such as infection, fever, dehydration, physical exertion, excessive cold exposure, or hypoxia .
Hemoglobin AA, normal hemoglobin;
hemoglobin AS, sickle cell trait;
hemoglobin SS, sickle cell disease.
Clumping of cells in the lungs (acute chest syndrome [ACS]) results in
decreased gas exchange, producing hypoxia, which leads to further sickling.
ACS and multiorgan failure are the leading common causes of death in children with SCD.
3 Clinical Manifestations of Sickle Cell Anemia
early. Signs and symptoms of sickle cell anemia usually don’t develop until after age 6 months because large amounts of fetal hemoglobin protect infants until then. Fetal hemoglobin has a higher oxygen concentration and inhibits sickling. Swollen hands and feet (hand-foot 4 syndrome) may be the first signs of sickle cell anemia in babies. The swelling is caused by sickle-shaped RBCs blocking blood flow out of their hands and feet.
5 Common laboratory and diagnostic studies ordered for the assessment of SCA include:
•Hemoglobin: baseline is usually 7 to 10 mg/dL; will be significantly
lower with splenic sequestration, ACS, or aplastic crisis
•Reticulocyte count: greatly elevated
•Peripheral blood smear: presence of sickle-shaped cells and target
cells 6 •Platelet count: increased
•Erythrocyte sedimentation rate: elevated
•Abnormal liver function tests with elevated bilirubin
X-ray studies or other scans may be performed to determine the extent
of organ or tissue damage resulting from vaso-occlusion.
Therapeutic Management
The therapeutic management children with SCA focuses on
preventing vaso_occlusive episodes and infection as well as other complications. Functional asplenia (decrease in the ability of the spleen to function appropriately) places the child at significant risk for serious infection with Streptococcus pneumoniae or other encapsulated organisms. Prophylactic antibiotics in the young child and appropriate immunization in all children with SCA can reduce the risk of serious infection
Treatment of vaso-occlusive episodes focuses on
• pain control.
• Oxygen administration is necessary during episodes of crisis to
prevent additional cell sickling.
• Adequate hydration with intravenous fluids is critical.
• Close monitoring of Hgb, Hct, and reticulocytes determines the point
7 at which transfusion of PRBCs becomes necessary.
• Electrolyte analysis is also necessary to ensure that
appropriate amounts of electrolytes are present in the serum. When
RBCs are administered, there is the potential for hemolysis of the cells, thus increasing the potassium level in the serum.
• Antibiotic therapy is necessary when infection is present.
Nursing Assessment
Elicit the health history, noting growth and development, frequency
and extent of vaso-occlusive crises, past hospitalizations, and treatment for pain crises.
Note history of immunizations, including pneumococcal, flu, and
meningococcal vaccinations.
Determine history of blood transfusions.
Document the current medication regimen.
Note history of recurrent infections.
Determine history of the present illness that results in a precipitating
event, such as hypoxia, infection, or dehydration. Note onset, character, and quality of pain, as well as relieving
factors.
8 Additional Medical Treatments for Some Children With
Sickle Cell Anemia
• Cholecystectomy may become necessary if gallstones develop.
• Splenectomy may be performed to prevent recurrence of splenic
sequestration if it is life threatening.
• Hydroxyurea increases the percentage of fetal hemoglobin (helping to
decrease vaso_occlusive events).
• L-glutamine in addition to hydroxyurea, or alone, decreases incidence
of painful vaso_occlusive episodes.
• Blood transfusions, though not routinely given to children with sickle
cell disease, are indicated in children with prolonged or widespread pain, apaplastic crisis, or splenic sequestration.
• Partial exchange transfusion may be used to rapidly lower the
circulating amount of Hgb SS in the event of stroke or acute chest syndrome.
• Hematopoietic stem cell transplantation is usually reserved for
children with an identical HLA-matched sibling (risk of death and incidence of graft-versus-host disease is high).
Nursing Management
Nursing care of the child with SCA focuses on
• preventing vaso-occlusive crises,
• providing education to the family and child.
9 • managing pain episodes.
• providing psychosocial support to the child and family.
• All children with SCA need ongoing evaluation of growth and
development to maximize their potential in those areas.
• Monitor school performance to detect neurodevelopmental
problems and seek intervention early.
Prevention or Early Recognition of Vaso-Occlusive Events
•Seek immediate attention for ANY febrile illness.
•Obtain vaccinations and penicillin prophylaxis.
•Encourage adequate fluid intake daily
•Avoid temperatures that are too hot or too cold
•Avoid overexertion or stress
•Have 24-hour access to physician, nurse practitioner, or facility
familiar with sickle cell care
•Contact medical provider promptly if you suspect a pain crisis is
developing.
•Seek medical attention immediately if any of the following develop:
•Child is pale and listless.
•Abdominal pain.
10 •Limp or swollen joints.
•Cough, shortness of breath, chest pain.
•Increasing fatigue.
•Unusual headache, loss of feeling, or sudden weakness.
•Sudden vision change.
•Painful erection that won’t go down (priapism).
Managing Pain During a Vaso-Occlusive Episode
Adequate pain management helps to decrease the child’s stress level .
Ensure the child is adequately hydrated with hypotonic fluid.
Nonsteroidal anti-inflammatory medications and acetaminophen are
often used for less severe pain.
Managing Vaso-Occlusive Episodes
•Treat any underlying conditions such as infection or injury. •Deficient fluid volume occurs as a result of decreased intake, increased fluid requirements during vaso-occlusive episode, and the kidney’s inability to concentrate urine.
Increasing fluid intake will dilute the blood and decrease its viscosity. To
11 promote hemodilution, provide 150 mL/kg of fluids per day or as much as double maintenance, either orally or intravenously.
•Maintain appropriate electrolyte and pH balance.
•Frequently evaluate respiratory and circulatory status. Encourage
incentive spirometry to decrease the incidence of ACS.
•Administer supplemental oxygen if the pulse oximetry reading is 92%;
oxygen supplementation in the absence of hypoxia is unnecessary and may inhibit erythropoiesis.
•Monitor level of consciousness and immediately report
changes.
Preventing Infection
To prevent severe infection in the child with SCA, a variety of
interventions are necessary. By 2 months of age, begin administration of oral penicillin V potassium as prophylaxis against pneumococcal infection. In the penicillin_allergic child, erythromycin may be used. Continue prophylaxis until at least age
5 years.
Administer childhood immunizations according to the currently
recommended schedule. To prevent overwhelming sepsis or meningitis
as a result of infection with S. pneumoniae, the child should receive pneumococcal conjugate vaccine annually after age 2 years. Meningococcal vaccination is also warranted .
12 Provide influenza immunization annually before the onset of flu
season (after 6 months of age) .
Supporting the Family and Child
As with any chronic illness, families of children with SCA need
significant support.
Thalassemia
Thalassemia is a genetic disorder that most often affects those of African
descent, but it also affects individuals of Caribbean, Middle Eastern, South
13 Asian, and Mediterranean descent . The genetics of
thalassemia are similar to those of SCD in that it is inherited via an autosomal
recessive process. Children with thalassemia have reduced production of normal hemoglobin.
There are two basic types of thalassemia ;
α and β. In α-thalassemia, synthesis of the α chain of the hemoglobin protein is
affected. Problems with the β chain occur more often, and the condition β-thalassemia can be divided into three
subcategories based on severity:
Thalassemia minor (also called β-thalassemia trait): leads to mild microcytic
anemia; often no treatment is required.
Thalassemia intermedia: child requires blood transfusions to maintain
adequate quality of life.
Thalassemia major: to survive the child requires ongoing medical attention, blood transfusions, and iron removal (chelation therapy).
14 The focus of this discussion will be on β-thalassemia major (Cooley anemia).
In β-thalassemia major, the β-globulin chain in hemoglobin synthesis is
reduced or entirely absent. A large number of unstable globulin chains
accumulate, causing the RBCs to be rigid and hemolyzed easily. The result is
severe hemolytic anemia and chronic hypoxia. In response to the increased rate of RBC destruction, erythroid activity is increased. The increased activity causes massive bone marrow expansion and thinning of the bony cortex.
Growth retardation, pathologic fractures, and skeletal deformities (frontal and
maxillary bossing) result.
15 Hemosiderosis (excessive supply of iron) is an additional complication of
significant concern. It occurs as a result of rapid hemolysis of RBCs, the
decrease in hemoglobin production, and the increased absorption of dietary iron
in response to the severely anemic state. The excess iron is deposited in the body’s tissues, causing bronze pigmentation of the skin, bony changes, and altered organ function, particularly in the cardiac system. Additional complications include splenomegaly, endocrine abnormalities, osteoporosis, liver and gallbladder disease, and leg ulcers. Left untreated, β-thalassemia major is fatal usually by age 5 years, but the use of blood transfusions and chelation therapy has increased the life expectancy of these children .
Therapeutic Management The therapeutic management for children with β-thalassemia includes
monitoring hemoglobin and hematocrit and transfusing PRBCs at regular
intervals. Blood iron levels are also monitored and iron chelation therapy is
provided.
Nursing Assessment Infants are usually diagnosed by 1 year of age and have a history of pallor,
jaundice, failure to thrive, and hepatosplenomegaly . Determine the
history of the present illness or whether the child is presenting for a routine blood transfusion. Note medications taken at home and any concerns that have arisen since the last visit. Inspect the skin, oral mucosa, conjunctivae, soles, and/or
16 palms for pallor. Note icteric sclerae or jaundice of the skin. Measure weight and height (or length) and plot on an appropriate growth chart. Observe
the child for bony deformities and frontal bossing . Measure oxygen saturation via pulse oximetry. Evaluate neurologic status, determining level of consciousness and developmental abilities.
Laboratory testing may reveal the following:
1.Hemoglobin and hematocrit are significantly decreased.
2.Peripheral blood smear shows prominence of target cells, hypochromia,
microcytosis, and extensive anisocytosis and poikilocytosis (variation in
the size and shape of the RBCs, respectively).
3.Bilirubin levels are elevated.
4.Hgb electrophoresis shows the presence of Hgb F and Hgb A2 only.
5.Iron level is elevated.
Nursing management
The nursing care of the child with thalassemia is primarily aimed at supporting the family and minimizing the effects of the illness. This includes administering blood transfusions and educating the family.
Administering Packed Red Blood Cell Transfusions.
Administer PRBC transfusions as prescribed to maintain an adequate level of
hemoglobin for oxygen delivery to the tissues and to suppress erythrocytosis in the bone marrow.
Monitor for reactions to the transfusions.
Excess iron is removed by chelation therapy. Administer the chelating agent
17 deferoxamine with the transfusion. Deferoxamine binds to the iron and allows it to be removed through the stool or urine. Oral deferasirox may also be prescribed and is generally well tolerated, with minimal GI side effects.
Educating the Family
Educate the child and family about the recommended regimen.
Ensure that families understand that adhering to the prescribed blood transfusion and chelation therapy schedule is essential to the child’s survival.
Chelation therapy must be maintained at home to continuously decrease the iron
levels in the body.
Teach family members to administer deferoxamine subcutaneously with a small
battery-powered infusion pump over a several-hour period each night (usually while the child is sleeping). If oral deferasirox is prescribed, instruct the family to dissolve the tablet in juice or water and administer it once daily.
Refer the family for genetic counseling and family support as needed.
