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ß Thalassemiaan Overview by Abdullatif
Husseini
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What is thalassemia?

• Thalassemia is a group of inherited disorders of
  hemoglobin synthesis characterized by a reduced
  or absent output of one or more of the globin
  chains of adult hemoglobin .
• The name is derived from the Greek words
  Thalasso Sea" and "Hemia Blood" in reference
  to anemia of the sea.

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Alpha (? ) thalassemia

• It appears when a person does not produce enough
  alpha chains for hemoglobin.
• It is mainly prevalent in the Africa, the Middle
  East , India, and occasionally in Mediterranean
  region countries.

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Beta (ß) thalassemia

• It appears when a person does not produce enough
  beta chains for hemoglobin.
• It is mainly prevalent in the Mediterranean
  region countries , such as Greece, Cyprus,
  Italy, Palestine and Lebanon.

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Types of Thalassemia

• ? thalassemia There are four types categorized
  according to the severity of their effects on
  persons with thalassemia.
• ß thalassemia There are 3 types categorized
  according to severity
• Thalassemia minor
• Thalassemia intermedia
• Thalassemia major

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Genetics of ß thalassemia

• Monogenic disorder a single gene disorder
• ß thalassemia result from over 150 mutations of
  the ß globin genes that result in the absence or
  a reduction of the ß globin chains

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Chromosomes
Source Thalassemia.com
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Transmission of ß thalassemia

• If a carrier (thalassemia minor) marries a
  non-carrier, on average half of their children
  will be carriers, but none will develop
  thalassemia major.

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Transmission ß of thalassemia- Cont

• However if two carriers marry, in each pregnancy
  there is a 25 chance of a non-carrier child, a
  50 chance of a carrier child (thalassemia
  minor), and a 25 chance of a child with
  thalassemia major.

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An example of inheritancea carrier married to
a normal person
Source Emirates Thalassemia Society
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An example of inheritance- Contmarriage
between two carriers
Source Emirates Thalassemia Society
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Types of ß thalassemia

• Thalassemia Minor (Trait).
• This can also be called (carrier state),
  meaning that the person carries the genetic trait
  for thalassemia.
• Such people usually practice normal life, but
  may suffer from a mild form of anemia.

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Types of ß thalassemia- Cont

• Thalassemia Intermedia.
• Caused by the reduced availability of beta
  chains in hemoglobin and can lead to moderate to
  severe anemia and an array of complications
  including bone deformities and splenomegaly.

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Types of ß thalassemia- Cont

• Thalassemia Major (Cooley's Anemia).
• Caused by the unavailability of beta chains in
  hemoglobin leading to a very severe and fatal if
  left untreated anemia.
• It requires regular blood transfusions leading
  to iron-overload which is treated with chelation
  therapy to prevent death from organ failure.

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ß thalassemia and malaria

• Thalassemic RBCs offers protection against severe
  malaria caused by Plasmodium falciparum.
• The effect is associated with reduced parasite
  multiplication within RBCs.
• Among the contributing factors may be the
  variable persistence of hemoglobin F, which is
  relatively resistant to digestion by malarial
  hemoglobinases.

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Signs and symptoms

• Thalassemia carriers (trait)
• Usually no signs or symptoms are apparent,
  except for a mild anemia.
• Carriers are usually initially detected
  through screening, or when performing routine CBC
  (complete blood count). Later it can be confirmed
  using hemoglobin electrophoresis.

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Signs and symptoms- Cont

• Thalassemia major
• Signs such as paleness and growth
  retardation, are readily detectable since the
  first year of life. Those are mainly due to
  severe anemia. Later bone deformities and
  hepato-splenomegaly develops.

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Laboratory diagnosis

• Thalassemia minor
• -Blood smear shows hypochromia and
  microcytosis (similar to Iron Deficiency Anemia).
• -Blood indices MCVlt 75 fl, Hb usuallygt 10,
  Hematocritgt 30, RDW lt 14.
• -Hemoglobin A2 often elevated gt 3, sometimes
  reaching 7-8.

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Laboratory diagnosis- Cont

• Thalassemia major
• -Blood smear shows profound microcytic
  anemia, with extreme hypochromia, tear drop,
  target cells and nucleated RBCs.
• -Hemoglobin may be very low at 3-4 g/dl.

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Blood picture of a ß thalassemia major patient
Source Cooleys Anemia Foundation
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Prenatal diagnosis

• Early prenatal diagnosis can be done using first
  fetal blood sampling, and later chorion villus
  biopsy and direct analysis of the globin genes.
• The error rate in experienced centers is now well
  under 1.

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Management and treatment

• Thalassemia minor (trait)
• No need for any treatment, since the carriers
  are usually symptomless.
• Thalassemia major
• The severe life-threatening anemia, requires
  regular life long blood transfusion, to
  compensate for damaged red blood cells.

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Management and treatment- Cont

• Thalassemia Major
• The continuous blood transfusion will
  eventually lead to iron overload, which must be
  treated with chelation therapy to avoid organ
  failure.

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Source Cooleys Anemia Foundation
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Management and treatment- Cont

• Thalassemia Major -Continued
• Other novel treatments like bone-marrow
  transplantation are very costly.
• New treatments includes the use of oral
  chelators, to replace the chelation treatment
  using Desferal delivered by infusion under the
  skin through a battery-operated pump.
• Gene therapy is also an option still
  researched

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Prevention efforts

• Pre marital screening to make sure that the
  couple are not both carriers.
• Provision of counseling and health education for
  the thalassemics, their families and the public .
• Provision of prenatal testing for thalassemia.
• Reduction of marriages between relatives.

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Thalassemia and migrants

• Countries with migrants coming from areas with
  high prevalence of thalassemia such as the
  Mediterranean region, should be aware of this
  problem.
• Families with thalassemia carriers may have
  increased number of cases including thalassemia
  major due to intermarriages between relatives,
  especially in closed communities

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Thalassemia and migrants -Cont

• The following recommendations are advised
• 1- Training physicians and medical staff on
  thalassemia diagnosis and treatment.
• 2- Provision of screening and counseling
  services for those exposed.
• 3- Provision of appropriate health care and
  management for thalassemia patients.

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Thalassemia and migrants -Cont

• 4- Overcoming the communication problems,
  including language barrier through utilizing
  translators and nurse practitioners.
• 5- Community educational programs, involving
  community leaders and providing social support.

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Problems commonly faced by thalassemia major
patients in developing countries

• Reduced availability of blood for transfusion.
• Reduced availability of Desferal pumps, less than
  third of the patients have access to pumps.
• High cost of treatment.

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Problems commonly faced by thalassemia major
patients in developing countries -Cont

• Limited services that blood banks are able to
  give.
• Unavailability of counseling services.
• Lack of experience and appropriate training among
  the health providers to handle thalassemia cases.

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Acknowledgement

• Acknowledgement
• I would Like to thank Dr. Hisham Darwish Dr.
  Bashar al-Karmi from
• Thalassemia Patients Friends Society (TPFS)-
  Palestine
• For the valuable information they provided.
• I would also like to express my sincere thanks
  for the Palestinian American Research Center
  (PARC) for providing me with a grant which
  allowed me to conduct research at the University
  of Pittsburgh, where I started preparing this
  lecture.