What is Thalassaemia?

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What is Thalassaemia?

By Fauzia Saeed, Psychologist, Thalassaemia Centre PRC, Punjab Branch,Lahore

Thalassaemia is an inherited blood disorder in which the body makes an abnormazorm of hemoglobin. Hemoglobin is the protein molecule in red blood cells that carries oxygen. The disorder results in excessive destruction of red blood cells, which leads to anemia. Anemia is a condition in which your body doesn’t have enough normal, healthy red blood cells.

Thalassaemia is inherited, meaning that at least one of your parents must be a carrier of the disease. It’s due to either a genetic mutation or a deletion of certain key gene fragments.

The two main forms of thalassaemia are alpha-thalassaemia and beta-thalassaemia. In alpha-thalassemia, at least one of the alpha globin genes has a mutation or abnormality. In beta-thalassaemia, the beta globin genes are affected.

Each of these two forms of thalassaemia has several distinct types. The exact form you have will affect the severity of your symptoms and prognosis

What Causes Thalassaemia?

Thalassemia occurs when there’s an abnormality or mutation in one of the genes involved in hemoglobin production. You inherit this genetic defect from your parents.

If only one of your parents is a carrier for thalassaemia, you may develop a form of the disease known as thalassaemia minor. If this occurs, you probably won’t have symptoms, but you’ll be a carrier of the disease. Some people with thalassaemia minor do develop minor symptoms.

If both of your parents are carriers of thalassaemia, you have a greater chance of inheriting a more serious form of the disease.

According to the Centers for Disease Control (CDC), thalassaemia is most common in people from Asia, the Middle East, Africa, and Mediterranean countries such as Greece and Turkey.

What Are the Symptoms of Thalassaemia?

Your symptoms will depend on the type of thalasseamia you have.

Thalassemia Minor

Thalassemia minor usually doesn’t cause any symptoms. If it does, it causes minor anemia.

Beta-Thalassemia

Beta-thalassaemia comes in two serious types, which are thalassaemia major, or  anemia, and thalassemia intermedia.

The symptoms of thalassaemia major generally appear before a child’s second birthday. The severe anemia related to this condition can be life-threatening. Other signs and symptoms include:

  • fussiness
  • paleness
  • frequent infections
  • a poor appetite
  • failure to thrive
  • jaundice, which is a yellowing of the skin or the whites of the eyes
  • enlarged organs

This form of thalassaemia is usually so severe that it requires regular blood transfusions.

Thalassaemia intermedia is a less severe form of beta-thalassaemia. People with thalassaemia intermedia don’t need blood transfusions.

Alpha-Thalassaemia

Alpha-thalassaemia also has two serious types, which are hemoglobin H disease and hydrops fetalis.

Hemoglobin H disease can cause bone issues. The cheeks, forehead, and jaw may all overgrow. Additionally, hemoglobin H disease can cause:

  • jaundice, which is a yellowing of the skin or the whites of the eyes
  • an extremely enlarged spleen
  • malnourishment

Hydrops fetalis is an extremely severe form of thalassaemia. It occurs before birth. Most individuals with this condition are either stillborn or die shortly after being born.

How Is Thalassaemia Diagnosed?

If your doctor is trying to diagnose thalassaemia, they’ll likely take a blood sample. They’ll send this sample to a lab to be tested for anemia and abnormal hemoglobin. A lab technician will also look at the blood under a microscope to see if the red blood cells are oddly shaped. Abnormally shaped red blood cells are a sign of thalassaemia. The lab technician may also perform a test known as hemoglobin electrophoresis. This test separates out the different molecules in the red blood cells, allowing them to identify the abnormal type.

Depending on the type and severity of the thalassaemia, a physical examination might also help your doctor make a diagnosis. For example, a severely enlarged spleen might suggest to your doctor that you have hemoglobin H disease.

What Are the Treatment Options for Thalassemia?

 

The treatment for thalassaemia depends on the type and severity of disease involved. Your doctor will give you a course of treatment that will work best for your particular case.

Some of the utilized treatments include:

  • blood transfusions
  • a bone marrow transplant (BMT)
  • medications and supplements
  • possible surgery to remove the spleen or gallbladder

Your doctor may instruct you not to take vitamins or supplements containing iron. This is especially true if you require blood transfusions. People who receive blood transfusions receive extra iron that the body can’t easily get rid of. Iron can accumulate in tissues, which can be potentially fatal.

You may also need chelation therapy if you’re receiving a blood transfusion. This generally involves receiving an injection of a chemical that binds with iron and other heavy metals. This helps remove extra iron from your body.

What Is the Long-Term Outlook?

If you have thalassaemia, your outlook depends on the type of the disease. People who have mild or minor forms of thalassaemia can typically lead normal lives.

Different forms of thalassaemia can be severe to mild. In severe cases, heart failure is a danger.

Your doctor can give you more information about your outlook and explain how your treatments can help improve your life or increase your expected lifespan.

Beta Thalassaemia Treatment & Management

Approach Considerations

The therapeutic approach to thalassaemia varies between thalassaemia minor and thalassaemia major.

Thalassemia minor

Patients with thalassemia minor usually do not require any specific treatment. Inform patients that their condition is hereditary and that physicians sometimes mistake the disorder for iron deficiency. Some pregnant patients with the beta thalassemia trait may develop concurrent iron deficiency and severe anemia; they may require transfusional support if they are not responsive to iron repletion modalities.

Thalassemia major

Treatment for patients with thalassemia major includes chronic transfusion therapy, iron chelation, splenectomy, allogeneic hematopoietic transplantation, and supportive measures. Emerging therapies include pharmacologic agents that induce fetal hemoglobin, Jak2 inhibitors to reverse splenomegaly, hepcidin-related compounds to improve iron metabolism, and gene therapy aimed at delivering the beta globin gene into cells by a viral vector.

Long-term transfusion therapy

The goal of long-term hypertransfusional support is to maintain the patient’s hemoglobin level at 9-10 g/dL, thus improving his or her sense of well being while simultaneously suppressing enhanced erythropoiesis. This strategy treats the anemia and suppresses endogenous erythropoiesis so that extramedullary hematopoiesis and skeletal changes are suppressed. Patients receiving long-term transfusion therapy also require iron chelation.

Blood banking considerations for these patients include completely typing their erythrocytes for Rh and ABO antigens prior to the first transfusion. This procedure helps future cross-matching processes and minimizes the chances of alloimmunization. Transfusion of washed, leukocyte-poor red blood cells (RBCs) at approximately 8-15 mL RBCs per kilogram (kg) of body weight over 1-2 hours is recommended.

Hapgood et al suggest that current recommendations lead to undertransfusion in males. As a result, males may be more likely to have extramedullary hematopoiesis and thus more likely to require splenectomy or to develop spinal cord compression, an uncommon but serious complication of paraspinal extramedullary hematopoiesis.

In their study of 116 patients (51 males and 65 females) with thalassemia major, males were receiving more units of RBCs per transfusion and had a higher annual transfusion volume, but with correction for weight, females were receiving a higher transfused volume per kg: 225 versus 202 mL/kg in males (P=0.028). Erythropoietin (EPO) levels were higher in males: 72 versus 52 mIU/mL (P=0.006). The incidence of splenectomy was higher in males (61%, vs 40% in females; P=0.031)

Hematopoietic stem cell transplantation

Allogeneic hematopoietic transplantation may be curative in some patients with thalassaemia major. The first successful allogeneic stem cell transplant from an HLA-identical sibling donor was reported in 1982.An Italian group led by Lucarelli has the most experience with this procedure.This group’s research documented a 90% long-term survival rate in patients with favorable characteristics (young age, HLA match, no organ dysfunction).

Transplantation-related issues such as graft versus host disease, graft failure, chronic immunosuppressive therapy, and transplantation-related mortality should be carefully considered prior to proceeding with this approach.

Diet and activity

Drinking tea may help to reduce iron absorption through the intestinal tract. Vitamin C may improve iron excretion in patients receiving iron chelation, especially with deferoxamine. However, anecdotal reports suggest that large doses of vitamin C can cause fatal arrhythmias when administered without concomitant infusion of deferoxamine.

Patient activity may be limited secondary to severe anemia

Beta Thalassaemia Medication

Medication Summary

Medical therapy for beta thalassemia primarily involves iron chelation. Each unit of transfused RBCs contains approximately 200 mg of elemental iron. Additionally, anemia and ineffective erythropoiesis down-regulates the synthesis of hepcidin.

The objective of iron chelation is to avoid the complications of iron overload such as cardiac and hepatic dysfunction. Chelation therapy significantly improves myocardial T2* and left ventricular function.

Deferoxamine is an intravenously administered chelation agent currently approved for use in the United States. Deferiprone, an oral chelation agent, has been approved for use in Europe and received approval in the United States in October 2011 for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. Deferasirox (Exjade), another orally administered chelation agent, was approved for use in the United States by the US Food and Drug Administration (FDA) in 2005. Guidelines on chelation treatment in thalassemia major have been published.

In general, iron chelation is started at age 2-4 years after 20-25 RBC units are transfused, with a serum ferritin level of greater than 1000 ?g/dL and a liver iron concentration (LIC) of greater than 3 mg iron/g dry weight as measured by liver biopsy or by noninvasive hepatic T2*MRI.

2017-04-26T12:34:50+00:00