THALASSEMIA

Submitted by : Jovan Pierre C. Ouano

Submitted to : Mark Gil T. Dacutan

I. Definition of the disease

Thalassemia is a group of genetic disorders theat result in inadequate normal Hb production.

Whereas IDA affects heme synthesis, thalassemia disrupts the synthesis of globin. These
disorders include alpha-thalassemia, a relatively benign and asymptomatic condition; beta-
thalassemia minor, a mild to moderate form of microcytic anemia; and beta thalassemia major,
a severe, microcytic, hypochronic anemia that may be fatal. These disorders also cause
hemolysis. All are chronic conditions.

Thalassemia is a quantitative problem of too few globins synthesized, whereas sickle-cell

anemia (a hemoglobinopathy) is a qualitative problem of synthesis of an incorrectly functioning
globin. Thalassemias usually result in underproduction of normal globin proteins, often through
mutations in regulatory genes. Hemoglobinopathies imply structural abnormalities in the globin
proteins themselves. The two conditions may overlap, however, since some conditions which
cause abnormalities in globin proteins (hemoglobinopathy) also affect their production
(thalassemia). Thus, some thalassemias are hemoglobinopathies, but most are not. Either or
both of these conditions may cause anemia.

There are two main types of thalassemia:

 Alpha thalassemia occurs when a gene or genes related to the alpha globin protein are
missing or changed (mutated).
 Beta thalassemia occurs when similar gene defects affect production of the beta globin
protein.

Alpha thalassemias occur most commonly in persons from southeast Asia, the Middle East,
China, and in those of African descent.

Beta thalassemias occur in persons of Mediterranean origin, and to a lesser extent, Chinese,
other Asians, and African Americans.

There are many forms of thalassemia. Each type has many different subtypes. Both alpha and
beta thalassemia include the following two forms:

 Thalassemia major
 Thalassemia minor
II. Causes/Risk Factors

Thalassemia disrupts the normal production of hemoglobin and leads to a low level of
hemoglobin and a high rate of red blood cell destruction, causing anemia. When
you're anemic, your blood doesn't have enough red blood cells to carry oxygen to your tissues
— leaving you fatigued.

Thalassemia is caused by defects in the genes that make hemoglobin. The only way to
get thalassemia is to inherit one or more defective hemoglobin genes from your
parents.

Alpha-thalassemia

Four genes are involved in making the alpha hemoglobin chain. You get two from
each of your parents. If one or more of the alpha hemoglobin genes are defective, you
develop alpha-thalassemia.

 One gene. If only one of your alpha hemoglobin genes is defective, you'll
have no signs or symptoms of thalassemia. But, you're a carrier of the disease
and can pass it on to your children.

 Two genes. If you have two defective alpha hemoglobin genes, thalassemia
signs and symptoms are mild. This condition is called alpha-thalassemia
minor.

 Three genes. If three of your alpha hemoglobin genes are defective, your
signs and symptoms will be moderate to severe. This condition is also called
hemoglobin H disease.

 Four genes. When all four alpha hemoglobin genes are defective, the
condition is called alpha-thalassemia major or hydrops fetalis. It usually
causes a fetus to die before delivery or shortly after birth.

Beta-thalassemia
Two genes are involved in making the beta hemoglobin chain. You get one from each
of your parents. If one or both of the beta hemoglobin genes are defective, you
develop beta-thalassemia.
  One gene. If one of your beta hemoglobin genes is defective, you have mild
signs and symptoms. This condition is called beta-thalassemia minor.

 Two genes. If both of your beta hemoglobin genes are defective, your signs and
symptoms will be moderate to severe. This condition is called beta-
thalassemia major or Cooley's anemia. Babies born with two defective beta
hemoglobin genes usually are healthy at birth, but develop signs and
symptoms within the first year of life.

RISK FACTORS

Factors that increase your risk of thalassemia include:

 Family history. Thalassemia is an inherited disorder, passed from parents to

children through defective hemoglobin genes.

 Ancestry. Thalassemia occurs most often in people of Italian, Greek, Middle

Eastern, southern Asian and African ancestry. Alpha-thalassemia affects
mainly people of Southeast Asian, Chinese and Filipino descent.

III. Pathophysiology

Normal hemoglobin is composed of two chains each of α and β globin. Thalassemia patients
produce a deficiency of either α or β globin, unlike sickle-cell disease which produces a specific
mutant form of β globin.

The thalassemias are classified according to which chain of the hemoglobin molecule is
affected. In α thalassemias, production of the α globin chain is affected, while in β thalassemia
production of the β globin chain is affected.

β globin chains are encoded by a single gene on chromosome 11; α globin chains are encoded
by two closely linked genes on chromosome 16. Thus in a normal person with two copies of
each chromosome, there are two loci encoding the β chain, and four loci encoding the α chain.
Deletion of one of the α loci has a high prevalence in people of African or Asian descent, making
them more likely to develop α thalassemias. β thalassemias are common in Africans, but also in
Greeks and Italians.
Alpha (α) thalassemias

The α thalassemias involve the genes HBA1 and HBA2, inherited in a Mendelian recessive
fashion. There are two gene loci and so four alleles. It is also connected to the deletion of the
16p chromosome. α thalassemias result in decreased alpha-globin production, therefore fewer
alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ
chains in newborns. The excess β chains form unstable tetramers (called Hemoglobin H or HbH
of 4 beta chains) which have abnormal oxygen dissociation curves.

Beta (β) thalassemias

Beta thalassemias are due to mutations in the HBB gene on chromosome 11 , also inherited in
an autosomal-recessive fashion. The severity of the disease depends on the nature of the
mutation. Mutations are characterized as (βo or β thalassemia major) if they prevent any
formation of β chains (which is the most severe form of β thalassemia); they are characterized
as (β+ or β thalassemia intermedia) if they allow some β chain formation to occur. In either case
there is a relative excess of α chains, but these do not form tetramers: rather, they bind to the
red blood cell membranes, producing membrane damage, and at high concentrations they form
toxic aggregates.

IV. Clinical Manifestations

 Fatigue

 Splenomegaly

 Jaundice from RBC hemolysis

 Bone marrow hyperplasia

 Hepatomegaly

V. Diagnostic Tests

A physical exam may reveal a swollen (enlarged) spleen.

A blood sample will be taken and sent to a laboratory for examination.

  Red blood cells will appear small and abnormally shaped when looked at under a
microscope.
 A complete blood count (CBC) reveals anemia.
 A test called hemoglobin electrophoresis shows the presence of an abnormal form of
hemoglobin.

A test called mutational analysis can help detect alpha thalassemia that cannot be seen with
hemoglobin electrophoresis.

Normal Results

In adults, these hemoglobin molecules make up the following percentages of total hemoglobin:

 Hb A: 95% to 98%
 Hb A2: 2% to 3%
 Hb F: 0.8% to 2%
 Hb S: 0%
 Hb C: 0%

In infants and children, these hemoglobin molecules make up the following percentages of total
hemoglobin:

 Hb F (newborn): 50% to 80%

 Hb F (6 months): 8%
 Hb F (over 6 months): 1% to 2%

Note: Normal value ranges may vary slightly among different laboratories. Talk to your doctor
about the meaning of your specific test results.

VI. Medical/Surgical Interventions

Treatment for thalassemia major often involves regular blood transfusions and folate
supplements.

If you receive blood transfusions, you should not take iron supplements. Doing so can cause a
high amount of iron to build up in the body, which can be harmful.

Blood transfusions cause a buildup of iron in the blood, which can

damage the heart, liver and other organs. To help the body get rid of the extra iron,
you may need to take medications known as "iron chelators." These medications may
be given as a pill or as an infusion under the skin. In some cases, a bone marrow
transplant or a stem cell transplant may be used to treat severe thalassemia.

Persons who receive significant numbers of blood transfusions need a treatment called
chelation therapy to remove excess iron from the body.

Bone marrow transplant may help treat the disease in some patients, especially children.

Medication

Medical therapy for beta thalassemia primarily involves iron chelation. Deferoxamine is the
intravenously or subcutaneously administered chelation agent currently approved for use in the
United States. Deferasirox (Exjade) is an oral iron chelation drug also approved in the US in
2005. Deferoprone is an oral iron chelator that has been approved in Europe since 1999 and
many other countries. It is available under compassionate use guidelines in the United States.

The antioxidant indicaxanthin, found in beets, in a spectrophotometric study showed that

indicaxanthin can reduce perferryl-HB generated in solution from met-Hb and hydrogen
peroxide, more effectively than either Trolox or Vitamin C. Collectively, results demonstrate
that indicaxanthin can be incorporated into the redox machinery of β-thalassemic RBC and
defend the cell from oxidation, possibly interfering with perferryl-Hb, a reactive intermediate in
the hydroperoxide-dependent Hb degradation.

VII. Nursing Interventions

 Watch for adverse reactions during and after RBC transfusions.

 Collaborative an antibiotic, and observe the patient for adverse reactions.
 Provide an adequate diet,
 Encourage the patient to drink plenty of fluids.
 Provide emotional support
 Explain the need for lifelong transfusions.

Patient teaching :

 Explain how to prevent infection e.g.  nutrition, wound care

 Tell about signs of hepatitis and iron overload, which are always possible with frequent
transfusions.
 Explain why child must avoid strenuous athletic activity to avoid pathologic fractures.
 References :

Medical-Surgical Nursing : Clinical Management for positive Outcomes, Vol. 2(pp.2288-2289),

By Joyce M. Black & Jane Hokanson Hawks

Brunner & Suddarths Textbook of Medical-Surgical Nursing, 12 th ed. Vol. 1(p.925), By Suzanne C.
Smeltzer , et. al

http://en.wikipedia.org/wiki/Thalassemia#Cause

http://www.scribd.com/doc/11824497/thalassemia

http://www.nlm.nih.gov/medlineplus/ency/article/000587.htm