Thalassemia overview

The thalassemias are a diverse group of genetic blood diseases. Thalassemia

is the most common inherited single gene disorder in the world. Scientists
and public health officials predict that thalassemia will become a worldwide
issue in the next century. With global improvements in childhood disease
prevention and treatment, more focus will be given to diagnosing disorders.
It is our hope that by providing education about the disease we can raise
awareness, encourage people to get tested for the trait, and spread
knowledge about comprehensive treatment.

The thalassemias are a diverse group of genetic blood diseases

characterized by absent or decreased production of normal hemoglobin,
resulting in a microcytic anemia of varying degree. The thalassemias have a
distribution concomitant with areas were malaria is common. People with
Thalassemia Minor are able to fight malaria better than those who do not
have it - therefore, in parts of the world where malaria existed Thalassemia
Minor increased. This was of great value in the past since malaria was
rampant and deadly. However, malaria is no longer a problem in many areas
of the world, and Thalassemia Minor has no advantage to people in these
areas. The alpha thalassemias are concentrated in Southeast Asia, Malaysia
and southern China. The beta thalassemias are seen primarily in the
Mediterranean Sea area, Africa and Southeast Asia. Due to global migration
patterns, there has been an increase in the incidence of thalassemia in North
America in the last ten years.

In the thalssemia patient, a mutation or deletion of the genes that control

globin production occurs. This leads to a decreased production of the
corresponding globin chains and an abnormal hemoglobin ratio. This
abnormal ratio leads to decreased synthesis of hemoglobin and the
expression of thalassemia. The globin that is produced in normal amounts
winds up in excess and forms red cell aggregates or inclusions. These
aggregates become oxidized and damage the cell membrane, leading to
hemolysis, ineffective erythropoiesis, or both. The quantity and properties of
these globin chain aggregates determine the characteristics and severity of
the thalassemia.
Thalassemia Minor
Your blood count may be a little lower than other people of your age and sex,
but this produces no symptoms. You were born with this condition and you
will have it all of your lifetime. There is no need for treatment and most
people who have inherited this are not sick and probably do not know they
have it. A mild form of Thalassemia minor may be mistaken for iron
deficiency anemia. Iron medicines are not usually necessary and will not help
your anemia. They could even be harmful if taken over a long period of time.

If you marry a person who does not have Thalassemia Minor, your children
may have Thalassemia Minor. If you marry a person who does have
Thalassemia Minor, some of your children may have Thalassemia Major. You
must decide if you want to take this risk in planning your family.

About 3-6% of Americans of Italian and Greek descent have Thalassemia

Minor. Thalassemia has also been found in people of many ethnic
backgrounds, so it cannot be called a Mediterranean disease. Other areas
affected are the Mid East, India, Pakistan and Southeast Asia.
Thalassemia Minor does not change.
Thalassemia Major
Thalassemia Major occurs when a person inherits two Thalassemia genes,
one from each parent. Both parents must have Thalassemia Minor. When two
individuals who have Thalassemia Minor marry, there is a 25% chance that
any pregnancy can result in a child with Thalassemia Major. Two of four
children will have Thalassemia Minor and 1 of 4 will be normal.

These chances are present with each pregnancy. Some families have had
only one ill child, while others have had all of their children affected.

Symptoms of Thalassemia Major

An infant with Thalassemia Major appears normal at birth. If a child is well for
the first five years of life, a diagnosis of Thalassemia Major is unlikely. The
double dose of two Thalassemia genes causes an anemia that is so severe
that regular blood transfusions must be given throughout life

A newborn with Thalassemia Major appears normal at birth. As they grow,

infants with Thalassemia Major exhibit paleness and fussiness. Weakness
and slow growth appear in the first or second years of life. The abdomen may
swell due to an enlarged liver and spleen. Changes occur in the appearance
of the face and head. The eyes appear slanted and the cheekbones become
prominent.
Treatment for Thalassemia Major
Treatment involves blood transfusions that must be given every 4 to 6 weeks
to sustain life.

Complications that may arise from regular blood transfusions include an

overload of iron build up in vital organs causing diabetes, liver disease and
heart failure. The spleen may become so enlarged or overactive that it has to
be removed surgically. In the past, many patients died in their teens due to
these complications.

Today, a medication called deferoxamine (Desferal) can remove iron from

the body, but must be given by slow infusions under the skin or in a vein
over 10-12 hours five to seven times a week using a battery driven pump.
Trials are under way with a new oral form of this medication and early results
have been encouraging. This promises to dramatically improve the quality of
life for sufferers of Thalassemia Major.

With transfusions and with the continuous use of Desferal, the life
expectancy of patients with Thalassemia Major has been greatly improved
with many patients reaching their thirties and even beyond.

Management of thalassemia is not enough. Researchers are investigating

two potentially curative treatments: bone marrow transplantation and gene
therapy. Both methods have shown promise.
Testing for Thalassemia

If a person has Thalassemia Minor, the cause of the slight anemia is known
and no other blood tests or treatments such as iron are needed. More
important, since individuals with Thalassemia Minor can pass the
Thalassemia gene to their
children, most people would like to know if there is a risk that their children
could inherit this severe blood disease.

A safe and reliable prenatal test to diagnose Thalassemia Major in a fetus as

early as 10-12 weeks after conception has been developed. Couples who are
at risk may

Other Names for Thalassemias

The various types of thalassemia have specific names related to the severity
of the disorder. Example-

• Alpha Thalassemias

• Alpha thalassemia silent carrier

• Alpha thalassemia minor, also called alpha thalassemia trait

• Hemoglobin H disease

• Alpha thalassemia major, also called hydrops fetalis

• Beta Thalassemias

• Beta thalassemia minor, also called beta thalassemia trait

• Beta thalassemia intermedia

• Beta thalassemia major, also called Cooley's anemia or beta-zero (ß0)

thalassemia
 • Beta-plus (ß+) thalassemia

Signs and Symptoms of Thalassemias

A lack of oxygen in the bloodstream causes the signs and symptoms of
thalassemias. The lack of oxygen occurs because the body doesn't make
enough healthy red blood cells and hemoglobin. The severity of symptoms
depends on the severity of the disorder. Alpha thalassemia silent carriers
generally have no signs or symptoms of the disorder. This is because the
lack of alpha globin protein is so minor that the body's hemoglobin works
normally.

Mild Anemia
People who have alpha or beta thalassemia trait can have mild anemia.
However, many people who have these types of thalassemia have no signs
or symptoms.

Mild anemia can make you feel fatigued (tired). Mild anemia caused by alpha
or beta thalassemia trait often is mistaken for iron-deficiency anemia.

Mild to Moderate Anemia and Other Signs

and Symptoms
People who have beta thalassemia intermedia have mild to moderate
anemia. They also may have other health problems, such as:

Slowed growth and delayed puberty. Anemia can slow down a child's growth
and development.

Bone problems. Thalassemia may cause bone marrow to expand. Bone

marrow is the spongy substance inside bones that makes blood cells. When
bone marrow expands, the bones become wider than normal. They may
become brittle and break easily.

An enlarged spleen. The spleen is an organ that helps your body fight
infection and remove unwanted material. When a person has thalassemia,
the spleen has to work very hard. As a result, the spleen becomes larger
than normal. This makes anemia worse. If the spleen becomes too large, it
must be removed.

Severe Anemia and Other Signs and

Symptoms
People who have hemoglobin H disease or beta thalassemia major (also
called Cooley's anemia) have severe thalassemia. Signs and symptoms occur
within the first 2 years of life. They may include severe anemia and other
health problems, such as:

• A pale and listless appearance

• Poor appetite

• Dark urine (a sign that red blood cells are breaking down)

• Slowed growth and delayed puberty

• Jaundice (a yellowish color of the skin or whites of the eyes)

• An enlarged spleen, liver, and heart

• Bone problems (especially bones in the face)

• Complications of Thalassemias

Better treatments now allow people who have moderate and severe
thalassemias to live much longer. As a result, these people must cope with
complications of these disorders that occur over time.

Heart and Liver Diseases

Regular blood transfusions are a standard treatment for thalassemias. As a
result, iron can build up in the blood (iron overload). This can damage organs
and tissues, especially the heart and liver.
Heart disease caused by iron overload is the main cause of death in people
who have thalassemias. Heart disease includes heart failure, arrhythmias
(irregular heartbeats), and heart attack.

Infection
Among people who have thalassemias, infections are a key cause of illness
and the second most common cause of death. People who have had their
spleens removed are at even higher risk because they no longer have this
infection-fighting organ.

Osteoporosis
Many people who have thalassemias have bone problems, including
osteoporosis (OS-te-o-po-RO-sis). This is a condition in which bones are weak
and brittle and break easily.

How Are Thalassemias Diagnosed

Doctors diagnose thalassemias using blood tests, including a complete blood
count (CBC) and special hemoglobin tests.

A CBC provides information about the amount of hemoglobin and the

different kinds of blood cells, such as red blood cells, in a sample of blood.
People who have thalassemias have fewer healthy red blood cells and less
hemoglobin than normal in their blood. People who have alpha or beta
thalassemia trait may have smaller than normal red blood cells.

Hemoglobin tests measure the types of hemoglobin in a blood sample.

People who have thalassemias have problems with the alpha or beta globin
protein chains of hemoglobin.

Moderate and severe thalassemias usually are diagnosed in early childhood.

This is because signs and symptoms, including severe anemia, occur within
the first 2 years of life.
People who have milder forms of thalassemia may be diagnosed after a
routine blood test shows they have anemia. Doctors may suspect
thalassemia if a child has anemia and is a member of an ethnic group that's
at increased risk for thalassemias. (For more information, go to "Who Is At
Risk for Thalassemias?")

Doctors also test the amount of iron in the blood to find out whether the
anemia is due to iron deficiency or thalassemia. Iron-deficiency anemia
occurs if the body doesn't have enough iron to make hemoglobin. The
anemia in thalassemia occurs because of a problem with either the alpha
globin or beta globin chain of hemoglobin, not because of a lack of iron.

Because thalassemias are passed from parents to children through genes,

family genetic studies also can help diagnose the disorder. These studies
involve taking a family medical history and doing blood tests on family
members.

The tests will show whether any family members have missing or altered
hemoglobin genes.

If you know of family members who have thalassemias and you're thinking of
having children, consider talking with your doctor and/or a genetic counselor.
They can help determine your risk for passing the disorder to your children.

If you're expecting a baby and you and your partner are thalassemia
carriers, you may want to consider prenatal testing.

Prenatal testing involves taking a sample of amniotic fluid or tissue from the
placenta. (Amniotic fluid is the fluid in the sac surrounding a growing
embryo. The placenta is the organ that attaches the umbilical cord to the
mother's womb.) Tests done on the fluid or tissue can show whether your
baby has thalassemia and how severe it may be.

How Are Thalassemias Treated

Treatments for thalassemias depend on the type and severity of the
disorder. People who are carriers or who have alpha or beta thalassemia trait
have mild or no symptoms. They need little or no treatment.

Doctors use three standard treatments for moderate and severe forms of
thalassemia. These include blood transfusions, iron chelation (ke-LAY-shun)
therapy, and folic acid supplements. Other treatments have been developed
or are being tested, but they're used much less often.

Standard Treatments

1.Blood Transfusions
Transfusions of red blood cells are the main treatment for people who have
moderate or severe thalassemias. This treatment gives you healthy red
blood cells with normal hemoglobin.

During a blood transfusion, a needle is used to insert an intravenous (IV) line

into one of your blood vessels. Through this line, you receive healthy blood.
The procedure usually takes 1 to 4 hours.

Red blood cells live only for about 120 days. So, you may need repeated
transfusions to maintain a supply of healthy red blood cells.
If you have hemoglobin H disease or beta thalassemia intermedia, you may
need blood transfusions on occasion. For example, you may need this
treatment when you have an infection or other illness, or when your anemia
is severe enough to cause tiredness.

If you have beta thalassemia major, or Cooley's anemia, you need regular
blood transfusions (often every 2 to 4 weeks). These transfusions will help
you maintain normal hemoglobin and red blood cell levels.

Blood transfusions allow you to feel better, enjoy normal activities, and live
into adulthood. This treatment is lifesaving, but it's expensive and carries a
risk of transmitting infections and viruses (for example, hepatitis). However,
the risk is very low in the United States because of careful blood screening.

2.Iron Chelation Therapy

Because the hemoglobin in red blood cells is an iron-rich protein, regular
blood transfusions can lead to a buildup of iron in the blood. This condition is
called iron overload. It damages the liver, heart, and other parts of the body.

To prevent this damage, iron chelation therapy is needed to remove excess

iron from the body. Two medicines are used for iron chelation therapy.

Deferoxamine is a liquid medicine that's given slowly under the skin, usually
with a small portable pump used overnight. This therapy takes time and can
be mildly painful. Side effects include problems with vision and hearing.

Deferasirox is a pill taken once daily. Side effects include headache, nausea
(feeling sick to the stomach), vomiting, diarrhea, joint pain, and fatigue
(tiredness).

3.Folic Acid Supplements

Folic acid is a B vitamin that helps build healthy red blood cells. You may
need to take folic acid supplements in addition to treatment with blood
transfusions and/or iron chelation therapy.
 4. Other Treatments
Other treatments have been developed or are being tested, but they're used
much less often.

• Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant replaces faulty stem cells with
healthy ones from another person (a donor). Stem cells are the cells inside
bone marrow that make red blood cells and other types of blood cells.

A stem cell transplant is the only treatment that can cure thalassemia. But
only a small number of people who have severe thalassemias are able to find
a good donor match and have the risky procedure.

5. Possible Future Treatments

Researchers are working to find new treatments for thalassemias. For
example, it may be possible someday to insert a normal hemoglobin gene
into stem cells in bone marrow. This will allow people who have thalassemias
to make their own healthy red blood cells and hemoglobin.

Researchers also are studying ways to trigger a person's ability to make fetal
hemoglobin after birth. This type of hemoglobin is found in fetuses and
newborns. After birth, the body switches to making adult hemoglobin.
Making more fetal hemoglobin may make up for the lack of healthy adult
hemoglobin.

Treating Complications
Better treatments now allow people who have moderate and severe
thalassemias to live much longer. As a result, these people must cope with
complications that occur over time.

An important part of managing thalassemias is treating complications.

Treatment may be needed for heart or liver diseases, infections,
osteoporosis, and other health problems.
 How Can Thalassemias Be Prevented
Thalassemias can't be prevented because they're inherited (passed from
parents to children through the genes). However, prenatal tests can detect
these blood disorders before birth.

Family genetic studies may help find out whether people have missing or
altered hemoglobin genes that cause thalassemias.

If you know of family members who have thalassemias and you're thinking of
having children, consider talking with your doctor and/or a genetic counselor.
They can help determine your risk for passing the disorder to your children.

Living With Thalassemias

Survival and quality of life have improved for people who have moderate or
severe thalassemias. This is because:

• More people are able to get blood transfusions now.

• Blood screening has reduced the number of infections from blood

transfusions. Also, treatments for other kinds of infections have
improved.

• Iron chelation treatments are available that are easier for some people
to take.

• Some people have been cured through blood and marrow stem cell
transplants.

• Living with thalassemia can be challenging, but several approaches

can help you cope.

Follow Your Treatment Plan

It's important to follow the treatment plan your doctor gives you. Get blood
transfusions as he or she recommends.

Take your iron chelation medicine. Iron chelation treatment can take time
and be mildly painful. However, it's important that you don't stop taking your
medicine. The leading cause of death among people who have thalassemias
is heart disease caused by iron overload. Iron buildup can damage your
heart, liver, and other organs.

Several chelation treatments are now available, including injections and pills.
Your doctor will talk with you about which treatment is best for you.

Take folic acid supplements if your doctor prescribes them. Folic acid is a B
vitamin that helps build healthy red blood cells. Also, talk with your doctor
about whether you need other vitamin or mineral supplements, such as
vitamins A, C, or D or selenium.

Get Ongoing Medical Care

Keep your scheduled medical appointments and get any tests that your
doctor recommends.

These tests may include:

• Monthly complete blood counts and tests for blood iron levels every 3
months

• Yearly tests for heart function, liver function, and viral infection (for
example, hepatitis B and C and HIV)

• Yearly tests to check for iron buildup in your liver

• Yearly vision and hearing tests

• Regular checkups to make sure blood transfusions are working

 • Other tests as needed (such as lung function tests, genetic tests, and
tests to match your tissues against a possible donor if a blood and
marrow stem cell transplant is being considered)

• Children who have thalassemias should receive yearly checkups to

monitor their growth and development. The checkups include a
physical exam, including a height and weight check, and any
necessary tests.

Take Steps To Stay Healthy

• Take steps to stay as healthy as possible. Follow a healthy eating plan
and your doctor's instructions about taking iron supplements.

• Get vaccinations as needed, especially if you've had your spleen

removed. You may need vaccines for the flu, pneumonia, hepatitis B,
and meningitis. Your doctor will advise you about which vaccines you
need.

• Watch for signs of infections (such as fever) and take steps to lower
your risk of infection. This step is very important if you've had your
spleen removed.

• Wash your hands often.

• Avoid crowds during cold and flu season.

• Keep the skin around the site where you get blood transfusions as
clean as possible.

• Call your doctor if a fever develops.

Seek Help and Support

If you or your child has thalassemia, you may have fear, anxiety, depression,
or stress. It's important to talk about how you feel with your health care
team. Talking to a professional counselor also can help. If you're feeling very
depressed, your doctor may recommend medicines or other treatments that
can improve your quality of life.

Joining a patient support group may help you adjust to living with
thalassemia. You can see how other people who have the same symptoms
have coped with them. Talk with your doctor about local support groups or
check with an area medical center.

Support from family and friends also can help relieve stress and anxiety. Let
your loved ones know how you feel and what they can do to help you.

Some teens and young adults who have thalassemias may have a hard time
moving from pediatric care to adult care. Doctors and other health
professionals who care for children who have thalassemias may not be
familiar with adult issues related to the disorder, such as certain
complications.

Also, it may be hard for adults who have thalassemias to find doctors who
specialize in treating the disorder. Ask your child's doctor to help you find a
doctor who can care for your child when the time comes to make the switch.
Planning and good communication can help this move go smoothly.

Key Points
• Thalassemias are inherited blood disorders. "Inherited" means that
parents pass the genes for the disorder on to their children.

• Thalassemias cause the body to make fewer healthy red blood cells
and less hemoglobin than normal. Hemoglobin is an iron-rich protein
that carries oxygen to all parts of the body and helps remove carbon
dioxide (a waste gas) from the body.

• People who have thalassemias can have mild to severe anemia. This
condition is caused by a lower than normal number of red blood cells
or not enough hemoglobin in the red blood cells.

• The two major types of thalassemia are alpha thalassemia and beta
thalassemia. There are different forms of each type.

• Thalassemias occur when the genes that control the production of

hemoglobin are missing or altered. Your body won't work well if your
red blood cells don't make enough healthy hemoglobin.

• Family history and ancestry are the two risk factors for thalassemias. If
your parents have missing or altered hemoglobin-making genes, you
may have thalassemia. Thalassemias occur most often among people
of Italian, Greek, Middle Eastern, Asian, and African descent.

• A lack of oxygen in the bloodstream causes the signs and symptoms of

thalassemias. Signs and symptoms may include mild to severe
anemia; slowed growth and delayed puberty; bone problems; an
enlarged spleen, liver, or heart; a pale and listless appearance; poor
appetite; dark urine; and jaundice (a yellowish color of the skin or
whites of the eyes). Symptoms depend on the type of thalassemia you
have. Silent carriers have no symptoms.

• Doctors diagnose thalassemias using blood tests, including a complete

blood count and special hemoglobin tests. Prenatal testing can show
whether an unborn baby as thalassemia and how severe it's likely to
be.

• People who have mild thalassemia often need little or no treatment.

There are three standard treatments for moderate and severe forms of
 thalassemia. These include blood transfusions, iron chelation therapy,
and folic acid supplements.

• Improved treatments now allow people who have moderate and

severe thalassemias to live longer. As a result, these people must cope
with complications of the disease that develop over time.
Complications include heart and liver diseases, infections,
osteoporosis, and other problems.

• Thalassemias can't be prevented because they're inherited. However,

these blood disorders can be found before birth through prenatal
testing.

• Living with thalassemia can be challenging, but several approaches

can help you cope. Follow your doctor's treatment plan, get ongoing
medical care, take steps to stay healthy, and seek help and support.