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   is due to a deletion or mutation in one or more of the four alpha globin gene copies. The more
genes affected, the less alpha globin produced. The four different types of alpha thalassemia include:
x Ô
 Ô
 . The silent carrier will have normal hemoglobin levels and red cell
indices but can pass on the affected gene to their offspring. Often, these individuals are identified only after
having a child with Hb H disease or alpha thalassemia trait (see below). The only way to diagnose this condition
is by DNA analysis.
x î

    . Patients who have alpha thalassemia trait have red blood cells that
are microcytic, hypochromic, have decreased MCV, and have a mild chronicanemia, but they do not generally
experience any other symptoms. This is an anemia that does not respond to iron supplements. Diagnosis of
alpha thalassemia trait is usually done by exclusion of other causes of microcytic anemia. Confirmatory testing
by DNA analysis is available but is not routinely done.
x 0
 0   . With this condition, the large decrease in the amount of alpha globin
chains produced causes an excess of beta chains, which then aggregate into beta tetramers (groups of 4 beta
chains), known as Hemoglobin H. Hb H disease can cause moderate to severe anemia and splenomegaly
(enlarged spleen). The clinical picture associated with Hb H disease is extremely variable, however. Some
individuals are asymptomatic while others have severe anemia. Hemoglobin H disease is found most often in
individuals of Southeast Asian or Mediterranean descent.
x î

  


  
 . This is the most severe form of alpha
thalassemia. In this condition, no alpha globin is produced, therefore, no Hb A or Hb F are produced. Fetuses
affected by alpha thalassemia major become anemic early in pregnancy. They become hydropic and frequently
have enlarged hearts and livers. This diagnosis is frequently made in the last months of pregnancy when a fetal
ultrasound indicates a hydropic fetus. About 80% of the time, the mother will have toxemia and can develop
severe postpartum bleeding (hemorrhage). Fetuses with alpha thalassemia major are usually miscarried,
stillborn, or die shortly after birth.

Alpha thalassemia is found most commonly in individuals with an ethnic background of Southeast Asia, Southern
China, the Middle East, India, Africa and the Mediterranean.

å   is due to mutations in one or both of the beta globin genes. There are 100 to 200 mutations that
have been identified but only about 20 are common. The severity of the anemia caused by beta thalassemia depends
on which mutations are present and on whether they decrease beta globin production (called beta+ thalassemia) or
completely eliminate it (called beta0 thalassemia). The different types of beta thalassemia include:
x å
  . A person with this condition has one normal gene and one with a mutation. They will
usually experience no health problems other than microcytosis and a possible mild anemia that will not respond
to iron supplements. This gene mutation can be passed on to an individual¶s children.
x 
  . In this condition, an affected person has two abnormal genes but is still producing
some beta globin. The severity of the anemia and health problems experienced depends on the mutations
present. The dividing line between thalassemia intermedia and thalassemia major is the degree of anemia and
the number and frequency of blood transfusions required to treat it. Those with thalassemia intermedia may
need occasional transfusions but do not require them on a regular basis.
x 
  


 
 î . This is the most severe form of beta thalassemia. The patient
has two abnormal genes that cause either a severe decrease or complete lack of beta globin production,
preventing the production of significant amounts of Hb A. This condition usually appears in an infant after three
months of age and causes life-threatening anemia. This anemia requires lifelong regular blood transfusions and
considerable ongoing medical care. Over time, these frequent transfusions lead to excessive amounts of iron in
the body. Left untreated, this excess iron can deposit into the liver, heart and other organs and can lead to a
premature death from organ failure.
Other forms of thalassemia occur when a gene for beta thalassemia is inherited in combination with a gene for
a hemoglobin variant. The most important of these are:
x Hb E ± beta thalassemia. Hb E is one of the most common hemoglobin variants, found predominantly in people
of Southeast Asian descent. If a person inherits one Hb E gene and one beta thalassemia gene, the
combination produces Hb E-beta thalassemia, which causes a moderately severe anemia similar to beta
thalassemia intermedia.

x HbS ± beta thalassemia or sickle cell ± beta thalassemia. Hb S is one of the most well known of the hemoglobin
variants. Inheritance of one Hb S gene and one beta thalassemia gene results in Hb S-beta thalassemia. The
severity of the condition depends on the amount of beta globin produced by the beta gene. If no beta globin is
produced, the clinical picture is almost identical tosickle cell disease.

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Complete blood count (CBC). The CBC is a snapshot of the cells and fluid in your bloodstream. Among other things,
the CBC will tell the doctor how many red blood cells are present and how much hemoglobin is in them. It will give the
doctor an evaluation of the size and shape of the red blood cells present, also called the red cell indices. These
include the mean corpuscular volume (MCV), a measurement of the size of the red blood cells. A low MCV is often
the first indication of thalassemia. If the MCV is low and iron-deficiency has been ruled out, the person may be a
thalassemia trait carrier.
Blood smear (also called peripheral smear and manual differential). In this test, a trained laboratorian examines a thin
layer of blood that is treated with a special stain, on a slide, under a microscope. The number and type of white blood
cells, red blood cells, and platelets can be evaluated to see if they are normal and mature. A variety of disorders
affect normal blood cell production. With thalassemia, the red blood cells are often microcytic (low MCV). Red cells
may also:
 x Be hypochromic
x Vary in size (anisocytosis) and shape (poikilocytosis)

x Be nucleated - normal, mature RBCs do not have a nucleus

x Have uneven hemoglobin distribution (producing ³target cells´ that look like a bull¶s-eye under the microscope).

The greater the percentage of abnormal looking red blood cells the greater the likelihood of an underlying disorder
and of impaired oxygen-carrying capability.

! . These may include: iron, ferritin, unsaturated iron binding capacity (UIBC), total iron binding capacity
(TIBC), and percent saturation of transferrin. These tests measure different aspects of the body¶s iron storage and
usage. They are ordered to help determine whether an iron deficiency is causing and/or exacerbating a patient¶s
anemia. One or more of them may also be ordered to help monitor the degree of iron overload in a patient with
thalassemia.
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! . This test measures the type and relative amounts of hemoglobin present in the
red blood cells. Hemoglobin A, composed of both alpha and beta globin, is the normal type of hemoglobin found in
adults. A greater percentage of Hb A2 and/or F is usually seen in beta thalassemia trait. Hb H may be seen in alpha
thalassemia due to Hb H disease.
DNA analysis. This test is used to investigate deletions and mutations in the alpha and beta globin producing genes.
Family studies can be done to evaluate carrier status and the types of mutations present in other family members.
DNA testing is not routinely done but can be used to help diagnose thalassemia and to determine carrier status.