What is Thalassemia
The thalassemias are a group of genetic blood disorders which affect normal hemoglobin production in the body. This means the body does not have the capacity to produce sufficient hemoglobin needed for various activities. This results in chronic anemia. Reduced hemoglobin production may be due to defects in either the beta-globin gene producing hemoglobin or the alpha-globin gene producing hemoglobin.
There are nearly 300 different mutations identified in many forms of thalassemia. The most prevalent mutations in India are beta-thalassemia and alpha-thalassemia though beta-thalassemia numbers are higher (estimated at nearly 100,000 thalassemia majors with 35-40 million carriers).
The clinical severity of thalassemia varies from thalassemia major (lifelong dependency on blood transfusion and other therapies), thalassemia intermedia (may require blood transfusions) and thalassemia minor (carriers who are otherwise healthy and normal).
Thalassemia is inherited from both parents which means mother and father have the carrier gene to produce a child with homozygous thalassemia who will present with signs and symptoms of the full-blown disease.
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Signs and Symptoms
Babies with thalassemia major usually present with symptoms from the age of 2-3 months. Check for the following symptoms in your baby if you think he/she may have thalassemia major:
- Baby is pale and lethargic and does not suckle adequately
- Baby is frequently coming down with infections like fever, vomiting and diarrhoea
- Baby fails to grow
If your baby has any of the above symptoms, please see your pediatrician immediately. He/she will refer you to a hematologist to confirm the diagnosis.
While babies with thalassemia major present with symptoms within the first six months of birth; children with thalassemia intermedia may not be symptomatic till the age of 4 or 5 years. In some cases, thalassemia intermedia has been diagnosed as late as the teens. Children/young adults with thalassemia intermedia may fall sick frequently, look pale and malnourished and exhibit facial features like prominent forehead and upper jaw. It is essential to diagnose thalassemia intermedia before it worsens to the point of cardiac defects.
Untreated, babies and children with thalassemia major may not survive beyond early childhood and usually die of cardiac failure. While children/young adults may survive with thalassemia intermedia up to adulthood, the quality of life is severely affected.
If you see signs and symptoms of thalassemia, do not hesitate to approach a pediatrician or physician (adults) who will help you get a diagnosis.
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If your pediatrician or physician suspects thalassemia, he/she will do some simple blood tests to confirm. Some of the blood tests include:
- Complete Blood Count (CBC) which will usually indicate hemolytic anemia with increased WBCs (white blood cell counts), low platelets (due to expansion of spleen) and microcytic anemia
- Iron studies usually indicate high serum iron concentration because of increased iron absorption from the gut
- Hemoglobin electrophoresis which will indicate high levels of fetal hemoglobin in thalassemia patients with low levels of adult hemoglobin since the globin chain has been disrupted because of the defective gene
While the above tests may suffice to get an initial diagnosis of thalassemia major, DNA testing for the child and parents is recommended to confirm the genotyping of the family
This is useful if the couple want to have more children who may be a HLA-match for their thalassemia child (bone marrow transplant). DNA analysis is also absolutely necessary for prenatal testing.
Blood transfusions - Thalassemia major and intermedia require lifelong treatment in the form of regular blood transfusions to make up for the reduced hemoglobin production in the body. Children/adults with thalassemia major usually require 1-2 units of blood every 15 days while children/adults with thalassemia intermedia may need 1 unit of blood every month. Some cases of intermedia require blood transfusion every 3 months or even 6 months to 1 year. The severity depends on each individual.
Iron chelation - Apart from regular blood transfusions, iron chelation therapy in the form of desferal (deferoxamine) subcutaneous infusion (with a pump), oral tablets like kelfer (deferiprone), asunra, desirox, defrijet or oleptiss (deferasirox) is required as the excess iron from blood transfusions accumulate in the vital organs causing severe damage and even death due to cardiac and liver failure.
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Your hematologist will be the best person to advise you on the best mode of iron removal.
You may be asked to do a combination of desferal injections and tablets. If you can tolerate tablets and your iron levels are maintained with just tablets, you will probably be asked to take tablets 5-6 days a week. Please note that any oral tablet comes with certain side effects and you need to keep your doctor informed if you experience side effects like joint pain, nausea, vomiting, gastric trouble or any other uneasiness. If you are on oral tablets, you will need to regularly (every 3 months) test for complete blood counts, liver and kidney function. You will also need to do a test called serum ferritin (to measure blood iron concentration) every 3-6 months to see if your iron chelation medicines are working level. Every year you may need to do a ferriscan to check the iron load in your liver and heart.
Regular supplements and medications - your doctor may put you on some supplements like folic acid, calcium, vitamin D, vitamin C and vitamin B12. It is advisable not to take any extra tablets or supplements without first consulting your doctor.
Regular vaccination - since children and adults with thalassemia are prone to infections, it is very important to be vaccinated regularly. The usual vaccines recommended for thalassemia are:
- Hepatitis B - full vaccination cycle with regular booster dose
- Typhoid - every 5 years
- Pneumonia - every 5 years
- Meningococcal - especially for those without a spleen
- Influenza - every year or as the doctor suggests
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Diet and exercise - people with thalassemia can lead a fairly normal life if transfused regularly and compliant with iron chelation. It is important to follow a diet which is low in iron which means avoiding iron-rich foods like red meat, egg yolk, ragi, jaggery and soya products.
While occasional indulgence is fine, regular consumption adds to the body’s iron overload.
Exercise is important to keep the bones healthy as iron affects the bones.
People with thalassemia can safely go for long walks, light jogging, floor exercises, swimming and dancing. Gym maybe permitted by the doctor with proper training from a gym instructor.
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Complications of thalassemia
Complications in thalassemia is mainly due to iron overload in the vital organs and poor chelation. If you are regularly transfusing without taking proper iron chelation, you are prone to complications from iron overload. Iron overload leads to hemosiderosis in various parts of the body. Complications include:
- Scarring in the liver and elevated liver functions along with enlarged liver
- Enlarged heart which can lead to sudden cardiac arrest
- Endocrine complications as the iron blocks the reproductive organs, endocrine glands like pancreas, thyroid and pituitary glands. This means a person with thalassemia can get diabetes, have issues like amenorrhea, poor growth, low hormone levels which may need hormone replacement therapy
- Bone complications like osteoporosis and osteopenia as excess iron affects calcium absorption capabilities
You can prevent all these complications if you chelate well and on time! A little bit of pain and discomfort now will save you from worse pain and complications which will affect your quality of life. Start with a solid chelation program right now! Talk to your doctor on what is best for you.
Another aspect of thalassemia complications you need to beware of are the blood-related infections due to lifelong blood transfusions. If you become infected with HIV, hepatitis B or C your hematologist will refer you to an infectious disease specialist and gastroenterologist who will put you on treatment. Hepatitis B and C have a cure with antiviral drugs which will fully clear your liver of the virus. HIV now has advanced retroviral drugs which will prevent full blown AIDS. If you have unfortunately been infected, do not hesitate to immediately talk to your doctor for early treatment. Remember it is not your fault that you became infected!
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As of today, bone marrow transplant is the only cure for thalassemia. A full HLA match with a sibling or unrelated donor is recommended preferably before the age of 12. The child must be well-mainted with regular transfusion, iron chelation and free from infections like hepatitis B and C. Your doctor will advise you on the procedure for bone marrow transplant.
Advances in gene therapy brings new hope for thalassemia as FDA-approved clinical trials have indicated positive outlook for a viral-vector mediated globin gene transfer to transfer a normal globin gene into a thalassemia patient.Another advance which brings hope to patients include the new investigational drug Luspatercept which stimulates hemoglobin production in people with thalassemia.
This drug is currently in clinical trials and expected to reach patients by 2019-2020.
Standard of Care and Best Transfusion Practices
Since blood-related infections like HIV, Hepatitis B and C are common; it is important for your transfusion centre or hospital to follow best blood banking and transfusion practices which include:
- Robust cross-matching of donor’s blood and patient’s blood
- Coombs test
- HIV, Hepatitis B and C
- Human T-Lymphotropic Virus (HTLV), West Nile virus and syphilis
Every unit of blood transfused must be saline washed with leukocyte-poor cells. It is advisable to use a leukocyte filter to eliminate even minimally present leukocytes which can cause blood transfusion reaction. In areas where filter is unavailable, saline washing is mandatory. In case of transfusion reaction like fever, chills, sweating, headaches, dizziness, hives and itching; the nursing care will administer an injection of phenergan to reduce the allergic reaction.
In case you experience symptoms like hematuria or bleeding in the urine post-transfusion, please report to your doctor immediately.
You may sometimes experience a swelling or blueness at the site of transfusion. You may be advised to use thrombophob gel to reduce some of this swelling.
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Standard of Care and Best Desferal Infusion Practices
Desferal for iron chelation works best with a portable, subcutaneous infusion pump. These pumps are usually available with your local Thalassemia society or your hospital pharma can advise you on availability.
For best results, nocturnal infusions for 8-10 hours is recommended. You will need the following for desferal infusion:
- 10 ml disposable syringe
- 5 ml or 10 ml distilled water depending on the number of injection vials used (desferal usually comes in 0.5 g vials)
- Scalp vein sets (gauge depends on your comfort) or thalasets (if available)
- Alcohol swabs
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Mix the distilled water (divided evenly among the number of desferal vials used. Ex: 2 ml per vial) into the desferal vial and allow it to dissolve completely till you get a clear, transparent liquid. Use your 10 ml syringe to draw the liquid in. Attach the scalp vein or thalaset to the syringe and then inject at the site (stomach around the navel area or thigh depending on your pain tolerance) after cleaning the site with an alcohol swab.
Stick leukoplast white plaster to keep the needle stable. Attach the syringe and scalp vein set to the infusion pump. The pump should be set to the time duration you prefer (say 8 hours or 10 hours).
You can insert the pump into the sling bag (provided with the infusion pump) and walk around or do your normal work. Remember to be careful and not get the needle off as you may get hurt.
If you experience redness, pain and swelling at the infusion site, you could use heating pads, hot water bottles and application of pain relief gels like lidocaine topical gel.
Tips for Thalassemia Intermedia
People with thalassemia intermedia may or may not require regular blood transfusions. However, remember that you will be absorbing iron from the gut faster than a thalassemia major so you need to test your serum iron frequently and maintain good chelation practices. People with thalassemia intermedia are advised to drink tea with every meal to prevent iron absorption from the gut.
Since thalassemia intermedia is prone to faster blood clotting, your doctor may put you on a small dose of a daily blood thinner medication. People with thalassemia intermedia may require spleen removal surgery to prevent splenomegaly and other complications. Post-splenectomy requires vigilance on infections and regular vaccines like pneumovax and meningococcal vaccine.
Tips for Thalassemia Minor
While you are a carrier, you are a healthy individual with none of the complications of thalassemia. You may occasionally experience low hemoglobin counts in which case you need to step up on folic acid supplements and adequate nutrition. Remember that as a thalassemia carrier, you should be alert and not take iron supplements to step up your hemoglobin counts.
Living with Thalassemia
A well-transfused, well-chelated person with thalassemia major can lead a perfectly normal life. Children with thalassemia go to school and engage in all activities including sports like basketball, cricket, volleyball and other running games. One can go to college, get a professional degree and take up any profession (except military service, flying, mining and other professions requiring hard labor). There are adults in India who are doctors, IAS officers, PhDs and journalists. There is also no bar on getting a girlfriend or a boyfriend! And getting married of course! Girls with thalassemia major can also have children provided they are well-maintained with no reproductive or endocrine complications.
While living with Thalassemia seems difficult at times balancing personal life, medical life, professional life and social life; you are not alone! It is not your fault that you have thalassemia! Connect with your local thalassemia community or join a Facebook group like ThalPal (https://www.facebook.com/groups/thalpal/). ThalPal is the best group for people with thalassemia with members across the globe with vast and varied experiences of dealing with thalassemia both clinically and socially. You can ask questions, clear your doubts about medical issues, get help (from charity groups giving out free iron chelators) or even find your soulmate in this group!
Prenatal Testing and Thalassemia
If you are a parent of a child with thalassemia and you want to go in for a second child, it is important to get a genotyping test for yourself, your partner and child. This is important to check if the unborn child is a thalassemia major or minor. Your child’s hematologist will probably refer you to a clinical geneticist for counseling and testing. After the child and parents are genotyped, the mother will undergo a test known as chorionic villi sampling (CVS) to test the unborn child. If you have planned a bone marrow transplant for your first child with thalassemia, you may also want to get a HLA-match test of the unborn sibling with the child.
If the unborn child is normal (not having inherited the defective globin gene from either parent) or a carrier (inherited just one copy of the defective gene), you will be asked to safely continue the pregnancy. In case the unborn child is also a thalassemia major, you have a choice of medical termination of pregnancy. This choice is left entirely to you and your family.