How thalassemia major is treated?

Patients with a severe form thalassemia are unable to produce normal red cells that are needed to carry oxygen throughout the body. Therefore, it affects their growth, development and their survival. Blood transfusion is a process where healthy red blood cells from a normal donor, are being given to such patients. So, these transfused red blood cells help to survive and maintain optimum growth and development for children with a severe form of thalassemia.

All patients with thalassemia do not require regular blood transfusions. However, some with a severe form of thalassemia need regular blood transfusions in order to survive. Individuals with either alpha thalassemia major or beta thalassemia major will require regular transfusions, But a person with a Beta and alpha thalassemia trait will not need any blood transfusion. However, beta thalassemia intermedia or hemoglobin H disease or E beta thalassemia might need blood transfusions occasionally or regularly.

The best time to begin transfusion is based on several factors; these include the child’s blood hemoglobin level and other symptoms and signs of low hemoglobin (anemia). When the anemia is affecting their body in the form of tiredness, increased heart rate, breathing difficulties, a blood transfusion should be given. The age of starting blood transfusion varies with each child. Even children who have the same type of thalassemia may start transfusion at different ages. Therefore regular checking of your child by your doctors is very important.
In general, children with alpha thalassemia major require transfusion while still in the womb and will continue transfusion after birth; those with beta thalassemia major will begin transfusions somewhere between six months and two years of age. For more moderate forms of thalassemia, such as beta thalassemia intermedia or hemoglobin H, there is no set age when transfusions begin. Some people with a moderate form of the disorder may not get transfused until they are adults, if ever.

Once transfusions begin in a child with thalassemia major, the hemoglobin level before transfusion should be between 8.5 and 10g/dL; after transfusion, it shouldn’t usually exceed 14g/dL. Targeting this level will determine how often transfusions are needed. Treating doctor will advice you exactly based on local guideline depend on situation of your child. This may slightly different in each child. Blood transfusion requirements also change as their age increases. In addition, the transfusion requirement may be affected by an illness or infection. Usually blood is transfused in every 4 to 6 weeks in thalassemia major once it is established.

The amount of blood given to each patient is usually based on the patient’s weight.

In addition to usual blood group, like ABO and RH grouping, detailed blood grouping should be done. It is to get the best possible matched blood to transfuse to your child in future. Transfusing the best matched blood will minimize the occurrences of transfusion reactions. Currently, all the blood before donation is tested for few viruses like HCV, HBV and HIV in majority of hospitals in the world. However, it is important that child has not had developed blood born infection like HCV, HBV and HIV before first blood transfusion. Therefore testing of these viruses is also important before first blood transfusion.

A Complete Blood Count (CBC) will measure your child blood
hemoglobin level and the blood sample will also be used for a “cross match” test. This is done to make sure that the blood going to be given to your child is a perfect match with your child’s blood

Thalassemia patients should receive packed red blood cells depleted of leukocytes (white blood cells). It should be usually less than 7 days old. It should be matched for the extended blood group of your child. Blood should be negative for HBV, HCV and HIV.

Blood transfusion is a life-saving treatment for many children with thalassemia major; but blood transfusions do have complications. There are three main problems.

1. 1. • Iron overload

As a consequence of regular blood transfusion, iron level in the blood can go up to a toxic level. It can cause significant damages to liver, heart, pancreas, thyroid gland, and bone. Removing excess iron through iron chelation (iron removal) reduces or prevents these complications.

1. 1. • Blood borne infections

Despite the high level of safety of donated blood, infections due to bacteria, viruses, or parasites can be transmitted to the patient through blood that is transfused. Currently, all the blood before donation is tested for few viruses like HCV, HBV and HIV in majority of hospitals in the world.

1. 1. • Transfusion reactions

Transfusion reactions are characterized by typical symptoms including high fever, nausea, diarrhea, chills, shakes, or a sudden drop in blood pressure. This is due to the fact that donated blood may contain some kind of a protein that the patient’s body doesn’t accept. Some reactions occur while your child is being transfused. The reactions can also occur after the transfusion, up to two weeks later. Such reaction is called delayed hemolytic transfusion reaction involving the breakdown of red blood cells. The patient may become yellowish due to increase in blood bilirubin level and may become pale because of the drop in blood hemoglobin level. In such cases, you should bring your child to the hospital to do further assessments. If you suspect at any time your child may be having a transfusion reaction, you should contact your doctor immediately to determine if any action needs to be taken.

You need to make sure that you child is fully immunized, especially for Hepatitis B virus infection. You also need to do annual blood test for viral infection including Hepatitis B, HCV and HIV.

Blood is a source of iron. Because, children with thalassemia major receive regular blood transfusions, Blood iron level will increase and gets accumulated in liver, heart, pancreas, and thyroid. This is called iron overload. In some children with thalassemia even without having regular blood transfusions, iron may get accumulated because their red cells are not produced effectively. This is also called iron overload. If this excess iron is not removed, it can get deposited in heart, liver, pancreas and thyroid gland. Therefore it can cause heart failure, liver failure, diabetes, and thyroid problems.

A group of medicines called iron chelation medicines are used to
 remove excess iron from patients with thalassemia major. This is called iron chelation therapy. With regular iron chelation therapy, problems of iron overload can be prevented or reduced. Adherence to the chelation therapy is very important and equally as important as a blood transfusion. It would improve long-term survival and quality of life of all patients with thalassemia major

There are 3 iron chelating medicine available include Deferoxamine (desferrioxamine), Deferasirox (brand name: Exjade, Jadanu) and Deferiprone (brand name: Ferriprox)

1. 1. 1. Deferoxamine Its usually administered by injecting under the skin typically over between 8 and 12 hours, and usually between five and seven nights per week. If body iron level is at very high level, it may be administered over 24 hours a day. In such cases, the drug may be administered intravenously.
      2. Deferasirox is taken by the mouth

Exjade: comes as a tablet, which dissolves to syrup form and taken immediately. It should be taken on an empty stomach once a day. It should not be chewed or swallowed.
Jadanu: this is Deferasirox in a tablet form. This does not need to be dissolved in liquids. It can be taken any time of the day as tablet.

1. 1. 1. Deferiprone (brand name: Ferriprox) This medication is also taken orally, usually in the form of a tablet to be taken three times per day. It may be given preferably with food
      2. Combination therapy is prescribed when we need to remove more iron from the body, if it is very high.

As in any other medicine, chelation drugs also have some side effects. Each child reacts to medicine differently so all children will not have all the side effects. However, benefits of chelation are more important than their side effects. Therefore, it should be given as prescribed.
Common side effects are

1. 1. • Nausea vomiting, diarrhea, heartburn, stomach pain
      • Pain in the arms, legs, back or joints
      • Headache, dizziness, fainting, seizures
      • Fast or pounding heartbeat
      • Red or brown discoloration of urine
      • Skin rash
      • Breathing difficulties.

Specific side effects are:

1. 1. • Desferal

Pain, swelling, reddening and itching of the skin at the site of the injection. Other side effects are dizziness, visual disturbances or hearing disturbances. Therefore, children that are receiving Desferal should have yearly hearing test and vision test .
If your child develops abdominal pain, vomiting and diarrhea, it may be due to an infection called Yersinia. This is one of the known complications of desferal. If this happens, please stop your Desferal injection and contact your hospital team.

1. 1. • Deferasirox

Deferasirox may cause damage to the kidneys or liver or severe bleeding in the stomach. It can also cause hearing and visual problems.
If your child experience any of the following symptoms, call your doctor immediately: decreased urination, swelling in the ankles, legs, or feet, excessive tiredness, breathing difficulty, confusion, yellowing of the skin or eyes, flu-like symptoms, pain in the abdomen, unusual bruising or bleeding, vomit that is bright red or looks like coffee grounds.

1. 1. • Deferiprone

Deferiprone may cause a decrease in the number of white blood cells. White blood cells help your child fight infection, so your child may be at risk of infection if the white cell count is low. If you experience any of the following symptoms of infection including fever, sore throat, mouth sores, flu-like symptoms, chills, or severe shaking stop taking Deferiprone and call your doctor immediately.

Typically, patients should start chelation after one or two years of regular blood transfusion; however, chelation treatment may vary with each patient who has thalassemia, so the type, amount, and timing of chelation should be tailored for each individual.

Various tests can be done to monitor the status of iron overload and the impacts of chelation therapy on your child.

• Blood Ferritin level

It is a simple blood test to monitor the patient’s blood iron level. Although serum ferritin measurement is an unreliable predictor of iron loading in thalassemia as they can be increased by inflammation and infection. What is more important is whether there is a general trend of ferritins going up or down over the period of several months. In general, most doctors set a goal of a ferritin level of 1,000 or below for their thalassemia patients.

1. 1. • MRI for liver iron concentration (LIC) (Ferriscans) and cardiac T2*function.

Liver Iron Concentration (LIC) provides the best measure of total body iron stores. It helps doctors to adjust the dose of chelation therapy. Measuring cardiac T2* is also an important and helpful investigation to monitor iron deposit in the heart as a significant number of transfused patients die from heart complications. However, the risk of heart complications will be decreased if the total body iron store is accurately monitored and maintained.

1. 1. • Audiology

A hearing test should be done prior to starting a chelator like desferral and desferasirox. A hearing test should be performed in the clinic regularly afterwards.

1. 1. • Ophthalmology

An annual evaluation by an ophthalmologist should be performed to rule out cataracts, or any vision problem

1. 1. • Kindney function and liver function

Kidney function and liver function test should be monitored monthly for patients on deferasirox and every three months for patients on deferoxamine.

1. 1. • CBC

Blood count must be monitored weekly with a CBC for patients on deferiprone.

1. 1. • Growth

Record height and weight monthly. Measure sitting height every six months to assess truncal shortening.

Splenectomy is a procedure where your child’s spleen is removed partially or fully. Because of the complications associated with splenectomy and lifelong care after the removal of the spleen, the current trend is to avoid splenectomy as much as possible.

Splenectomy is indicated when there is a hypersplenism. Hypersplenism means an annual transfusion volume exceeding 225 to 250 mL/kg per year with packed red blood cells (hematocrit 75 percent). Patients with hypersplenism may have big spleen and some degree of low neutrophil and platelets. Splenectomy can be considered if there are clinically significant complications such as low blood count and marked enlargement of the spleen due to hypersplenism.

Severe infection is the potential risk of splenectomy. Therefore it should be avoided in children younger than five years.

Patients must receive adequate immunization against Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitides prior to surgery.

Adverse effects of splenectomy on blood clotting, should be recognized and dealt with after splenectomy.
After splenectomy, patients should receive oral penicillin prophylaxis to prevent infections and should be instructed to seek urgent medical attention for a fever.