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Thalassemia

Our Hemoglobinopathy multidisciplinary team provides comprehensive services to patients with Alpha Thalassemia – Hemoglobin H Disease, Beta Thalassemia Major (including Hemoglobin E-Beta Thalassemia) or Intermedia – who require frequent blood transfusions (monthly blood transfusions for Major patients, less often for Intermedia patients). Common ongoing health issues for thalassemia patients are covered in our program, including growth and development, iron overload (including organ dysfunction from iron deposition in many organs) management including treatment and screen for organ dysfunction, genetic counseling, psychological services and blood transfusion complications.

Our patients are seen on Wednesdays between 10 a.m. - 4 p.m. weekly on the B1 Floor of the University of Michigan Comprehensive Cancer Center. Blood transfusions take place right next door in our Pediatric Infusion Center in the Cancer Center. We also provide genetic counseling for any families as it relates to carrier (“trait”) status for alpha or beta thalassemia.

Thalassemia is the name of a group of genetic blood disorders that is the result of a decreased production of alpha globin chain (alpha thalassemia) or beta globin chain (beta thalassemia). Since hemoglobin (which carries oxygen to our tissues) is made up of two alpha globin chains and two beta globin chains, a decreased production of either one of these chains will result in some form of anemia (less hemoglobin in blood).

The Silent Carrier will experience no health problems in his/her lifetime. This carrier state is diagnosed by deduction when a "normal" individual has a child with Hgb H disease or with microcytic anemia consistent with alpha thalassemia trait. An unusual case of the silent carrier state is the individual who carries the Hemoglobin Constant Spring mutation. This is an elongated globin due to a termination codon mutation. Individuals who have this mutation have normal red blood cell indices but can have children who have Hgb H-Constant Spring disease if the other parent has alpha thalassemia trait. Two Constant Spring carriers can also pass on their genes to have a child with Homozygous Constant Spring, a condition that has similar clinical implications as Hemoglobin H disease.

Alpha Thalassemia Trait is characterized by two functional genes that code for the production of alpha globins. The two genes can either occur on the same chromosome (cis-type) or on each of the pair (trans-type). Cis-type tends to be found in individuals of Asian descent, while trans-type tends to run in individuals of African descent. Cis-type can be co-inherited with another cis-type or hemoglobin H disease to result in alpha thalassemia major, or hydrops fetalis. Individuals who have alpha thalassemia trait are identified by microcytosis, erythrocytosis, hypochromia and mild anemia. In children, there are no markers such as Hgb A2 and Hgb F to make the diagnosis. (One exception is the case where both of the deletions occur on the same chromosome and zeta globin is expressed in carriers. This is most common in Southeast Asians.) The diagnosis is one of exclusion. The clinician should be satisfied with the presumed diagnosis if the above criteria are met. During pregnancy, the microcytic anemia can be mistaken for anemia of pregnancy.

Hemoglobin H Disease is characterized by one functional gene that codes for the production of alpha globins. Hemoglobin H does not function as a normal hemoglobin and has a high oxygen affinity. Individuals who have Hgb H generally have a persistent stable state of anemia, which may be accentuated by increased hemolysis during viral infections and by exposure to oxidant medications, chemicals and foods such as sulfa drugs, benzene and fava beans (similar to individuals who have G6PD deficiency).

Beta Thalassemia 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 whether they decrease beta globin production (called beta+ thalassemia) or completely eliminate it (called beta0 thalassemia). The different types of beta thalassemia include:

Beta Thalassemia Trait. A person with this condition has one normal gene and one with a mutation. The person will usually experience no health problems other than microcytosis (small red blood cells) and a possible mild anemia that will not respond to iron supplements. This gene mutation can be passed on to an individual’s children.

Thalassemia Intermedia. 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 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.

Thalassemia Major (also called "Cooley's Anemia"). 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 Hgb A. This condition usually appears in an infant after 3 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.

Bone Marrow Transplantation
Bone marrow transplantation has been used here at the University of Michigan and nationally to cure patients with sickle cell disease or thalassemia.

Sibling Matched Bone Marrow Transplantation: The University of Michigan Pediatric Blood and Marrow Transplantation Program has successfully transplanted and cured patients with Beta Thalassemia Major from sibling bone marrow donors. Patients with beta thalassemia major or intermedia are eligible for sibling matched bone marrow transplantation through our Pediatric Bone Marrow Transplantation Program. Once a patient with beta thalassemia major or intermedia is deemed eligible for bone marrow transplantation, we will perform bone marrow typing studies (a simple blood test) on the sibling(s) of the patient to determine if there is a “bone marrow match” or “ HLA Match” transplantation. If there is a match, we will refer them to our Pediatric Blood and Marrow Transplantation Program for future evaluation and consideration.

Please contact us for any questions regarding the use of bone marrow transplantation in Thalassemia.

Chelation Therapy
To help remove excess iron, patients undergo "iron chelation therapy," in which a drug is introduced into the body; the drug binds with excess iron and removes the excess iron through the urine or stool. For many years, the only Food and Drug Administration-approved iron chelator was Desferal, which has to be administered through a painful and difficult infusion process. When using Desferal, a needle is attached to a small battery-operated infusion pump and worn under the skin of the stomach or legs five to seven times a week for up to twelve hours.

In November 2005, the FDA approved an oral chelator, Exjade. This pill is dissolved in water or juice and drunk once a day. Many patients now have a treatment option in terms of chelators, and it is hoped that more options will become available in the coming years.

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