THALASSEMIA MAJOR (COOLEY'S ANEMIA)

Thalassemia major is the most severe of the beta-thalassemia syndromes and represents the
homozygous form of the disease. Beta-thalassemia (-thalassemia) refers to an inherited
hemolytic anemia, characterized by a reduction or absence of the -globulin chain in
Hbsynthesis. This RBC has a decreased amount of Hb, resulting in a fragile RBC with a short
life span. Most prevalent in the Mediterranean basin, Middle East, Southeast Asia, and Africa. In
the United States, it is most common in children of Italian, Greek, and Southeastern Asian
ancestry. About 1,400 people in the United States are affected.
Pathophysiology and Etiology

Genetically determined, inherited diseaseautosomal recessive pattern of inheritance.

Insufficient -globin chain synthesis allows large amounts of unstable chains to

accumulate.

The precipitates of beta chains that form cause RBCs to be rigid and easily destroyed,
leading to severe hemolytic anemia and resultant chronic hypoxia.

Erythroid activity is significantly increased in an attempt to overcome the increased rate

of destruction, resulting in enormous expansion of bone marrow, thinning of bony cortex
leading to:
o Skeletal deformities: frontal and maxillary bossing.
o Growth retardation.
o Pathologic fractures.

Rapid destruction of defective RBCs, decreased production of Hb, and increased

absorption of dietary iron caused by the body's response to anemia result in an excess
supply of available iron (hemosiderosis), which deposits iron on organ tissues, resulting
in decreased function (especially cardiac).

In response to the low level of adult Hb, large concentrations of Hb F, which does not
contain alpha chains, are produced; Hb F does not hold oxygen well.

Clinical Manifestations

Onset is usually insidious, with symptoms noted between ages 3 and 6 months when Hb
F is diminished.

Symptoms are primarily related to the progressive anemia, expansion of the marrow
cavities of the bone, and the development of hemosiderosis.

Early symptoms commonly include progressive pallor, poor feeding, and lethargy.

Further signs of progressive anemia include headache, bone pain, exercise intolerance,
jaundice, and protuberant abdomen caused by hepatosplenomegaly.

Diagnostic Evaluation

Hb leveldecreased.

RBCsincreased number.

Low mean corpuscular volume and mean corpuscular hemoglobin

concentrationmicrocytosis and hypochromia.

Peripheral blood smearmany anisopoikilocytes, nucleated RBCs.

Reticulocyte countlow, usually less than 10%.

Hemoglobin electrophoresiselevated levels of HbF and HbA2; limited amount of

HbA.

Management

Frequent and regular blood transfusions of packed RBCs to maintain Hb levels above 10
g/dL.
o Washed, packed RBCs are usually used to minimize the possibility of transfusion
reactions. If unavailable, leukofiltered cells can be substituted.
o The frequency and amount of transfusions depend on the size of the child, usually
10 to 15 mL packed RBC per kg body weight every 2 to 3 weeks.

Iron chelation therapy with deferoxamine (Desferal) reduces the toxic adverse effects of
excess iron; increases iron excretion through urine and feces.
o I.V. infusion of 100 to 150 mg/kg per day given in hospital during blood
transfusion or for child with high ferritin level and poor compliance with home
chelation therapy.
o Subcutaneous infusion of 50 mg/kg per day usually infused 12 hours during night
for home therapy.

Splenectomy.

Supportive management of complications.

Bone marrow transplants may be considered. Young patients with few complications are
the best candidates.
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Prognosis is poor because no cure is known; commonly fatal in late adolescence or early
adulthood.

Complications

Splenomegalyusually requires splenectomy; overwhelming postsplenectomy infection

rate seen in 25% of these patients.

Growth retardation in second decade.

Endocrine abnormalities:
o Delayed development of secondary sex characteristicsmost boys fail to
undergo puberty; most girls experience alteration in menstruation.
o Diabetes mellitus is commonly seen in older patients, related to iron deposits on
the pancreas.
o Hypermetabolic rate results in increased temperature and lethargy.

Skeletal complicationsbecome less common because of early transfusion therapy and

maintenance of Hb levels above 10 g/dL:
o Frontal and parietal bossing (enlarging).
o Maxillary hypertrophy, leading to malocclusion.
o Broad ribs.
o Premature fusion of epiphyses of long bones.
o Generalized skeletal osteoporosis.
o Pathologic fractures of the long bones and vertebral collapse.

Cardiac complications:

o Fibrosis and hypertrophy.

o Pericarditis.
o Heart failureusual cause of death.

Liver enlargementfibrosis, coagulation abnormalities, and eventually cirrhosis.

Gallbladder diseasegallstones are common by late adolescence; may require

cholecystectomy.

Megaloblastic anemiacaused by sporadic folic acid deficiency from increased use by

hyperplastic marrow.

Skinbronze pigmentation caused by iron deposits in the dermis; jaundice.

Leg ulcers.

Nursing Assessment

Obtain family history of thalassemia or unexplained anemia or heart failure.

Perform whole body examination to assess for anemia and systemic complications of
thalassemia.

Measure growth and development parameters.

Nursing Diagnoses

Ineffective Tissue Perfusion related to abnormal Hb

Chronic Pain related to progression of disease in bone

Activity Intolerance related to bone pain, cardiac dysfunction, and anemia

Risk for Infection related to progressive anemia and splenectomy

Deficient Knowledge related to iron chelation therapy

Disturbed Body Image related to endocrine and skeletal abnormalities

Ineffective Family Coping related to poor prognosis

Nursing Interventions

Maximizing Tissue Perfusion

Administer blood transfusions as ordered.

o Observe for signs of transfusion reaction (increased chance caused by frequency)
including allergic, febrile, septic, circulatory overload, and hemolytic reactions.
o Allergic reactions usually occur within 15 to 20 minutes of start of the
transfusion, although delayed reactions may occur up to several months later.

Monitor cardiovascular status for complications.

o Monitor apical pulse, BP, and respirations.
o Assess for edema.
o Auscultate heart sounds for gallop and lungs for rales.
o Assess extremities for ulcer formation.

Refer to care of the child with heart failure (see page 1476).

Relieving Bone Pain

Monitor CBC as ordered and report Hb levels of less than 10 g/dL.

Elevate lower extremities.

Provide warm baths or soaks.

Administer or teach proper administration of NSAIDs, such as ibuprofen (Motrin) or

naproxen (Naprosyn). Use carefully and monitor liver enzymes in patients with liver
complications.

Minimizing Activity Intolerance

Encourage participation in activities that do not require significant strenuous activity. Full
participation in some activities, especially with peers, will increase self-esteem.

Facilitate physical and occupational therapy consultation to develop an acceptable

exercise plan.

Assist the parents in contacting the child's school and develop a plan of gym activities,
classes, and rest periods that allow the greatest level of participation and slowly develop

endurance. Advise parents that during the week of the scheduled transfusion, the fatigue
will be greatest, so gym and other exertional activities should be modified.

Suggest that driving the child to school and providing adequate rest at home will provide
her with more energy for school activities.

Discourage participation in contact or other sports that increase the child's risk for a
fracture (skateboarding, football, soccer).

Preventing Infection

Explain to parents that after splenectomy, child has increased susceptibility to infection
and should be maintained on oral penicillin prophylaxis.

Make sure that child has been vaccinated against H. influenzae, pneumococcal, and
meningococcal infections before
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splenectomy, and encourage yearly trivalent influenza vaccination.

Encourage prompt medical attention for fever or signs of infection. Fever of 102 F
(38.9 C) should be reported immediately and I.V. broad-spectrum antibiotics, such as
ceftriaxone (Rocephin), started.

Promoting Understanding and Compliance

Explain to family that deferoxamine (Desferal) is used as a chelating (binding) agent to

decrease iron deposits in tissues and to increase iron excretion through urine and feces.

Administer I.V. deferoxamine as ordered.

o Infuse slowly, during 8 to 24 hours, through peripheral line or implanted infusion
device, via volumetric pump.
o Have emergency resuscitation equipment nearby in case severe allergic reaction
occurs.

Teach administration of subcutaneous deferoxamine and initiate referral for home

infusion therapy.
o Infuse during 12 hours, usually overnight.

o Pick a site in the subcutaneous tissue in the abdomen, thigh, or arm, and insert a
small subcutaneous needle attached to a syringe pump.
o EMLA, a topical anesthetic, may be used to decrease pain at the insertion site.
o Infusion site may become red, hard, and painful; must rotate sites. Warm soaks to
area are helpful.
o Because allergic reaction may occur, instruct parents to give antihistamine, and if
necessary, epinephrine.

Be alert for visual and hearing deficits associated with use of deferoxamine and
encourage follow-up visits for periodic visual and audiometric testing.

NURSING ALERT
Because of the excess iron deposition in children with thalassemia, dietary iron should be
decreased as much as possible.
Improving Body Image

Explore the child's feelings of being different from other children.

Encourage the child to express feelings through the use of play: art, role playing.

Give positive reinforcement regarding appearance.

Encourage socialization and peer interaction.

Suggest endocrine consultation for delayed growth and puberty and craniofacial specialist
for bony abnormalities.

Encourage the use of makeup, clothing, and hairstyles that will make the adolescent
appear older.

Suggest support group or individual counseling as needed.

Improving Family Coping Strategies

Alleviate the child's anxieties about illness by providing explanation in a way the child
can understand.

Use role-playing and play activities to identify concerns.

Assist parents in strengthening coping mechanisms, such as support network, problem

solving, and planning ahead.

Help identify resources for financial support, medical supplies, respite care, etc.

Encourage parents to continue education of child and obtain vocational planning, if

realistic.

Encourage parents to set limits and to provide discipline for child that is consistent with
that for other children in family.

Provide supportive care to the dying child (see page 1393).

Encourage bereavement support for parents, siblings, and family.

Family Education and Health Maintenance

Discuss the genetic implications of thalassemia and refer for genetic counseling.

Provide detailed instruction about:

o Prevention and prompt treatment of infections.
o Medications.
o Home chelation therapy.
o Dietary modifications to limit iron intake.
o Activity restrictions, including avoidance of activities that increase the risk of
fractures.
o Signs of complications.

Encourage parents to provide information about the child's condition to significant adults
who are involved with the child (teacher, school nurse, baby-sitter, Scout leader).

For additional information and support, refer to Cooley's Anemia Foundation,

http://www.thalassemia.org.

Evaluation: Expected Outcomes

BP stable; no edema; no leg ulcers

Verbalizes better tolerance of pain

Reports increased participation in activity, less fatigue

Afebrile; immunizations current

Parents verbalize purpose of chelation therapy, treatment of allergic reaction, how to treat
site; demonstrating correct technique for infusion

Verbalizes interest in appearance and positive statements about self

Parents seek help from support group and social worker; discuss illness with child and
siblings

Pathophysiology
Three mechanisms work together to facilitate healing when a blood vessel is injured
(Box 1). First, the blood vessel constricts to limit the volume of blood that is lost.
Second, circulating platelets form a plug at the site of injury. Finally, the blood
undergoes coagulation. A number of clotting factor proteins, defined by Roman
numerals, must be activated in sequence for coagulation to take place. This process
allows the platelet plug to be stabilised by a fibrin matrix that is formed over its
surface, thereby ensuring that the vessel wall can heal (Waugh and Grant, 2002).
Factors VIII and IX are only two of the 13 proteins that are involved in the cascade
process of coagulation. If there is an absence or deficiency of any of these proteins
the coagulation process will be initiated but not completed: the platelet plug will
remain unstable and bleeding will continue over a prolonged period of time.