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Transfusion Therapy Lifelong transfusions address anemia and enable survival, but do not correct the genetic defect of transfusion-dependent beta‑thalassemia (TDT)1

Lifelong Supportive Care With Regular Transfusions is Necessary in TDT1,2

Patients with TDT require lifelong supportive care with regular red blood cell transfusions. Transfusion and iron chelation therapy have significantly improved the survival of TDT patients over the last few decades.1,2,3

Patients with transfusion‑dependent beta‑thalassemia typically require transfusions every two to five weeks, with the goal, according to TIF guidelines, to correct anemia, suppress ineffective erythropoiesis, and enable survival.1

Current TIF guidelines for TDT recommend lifelong transfusions, typically every 2 to 5 weeks, in patients who meet the following criteria:1

  • Confirmed diagnosis of thalassemia
  • Hemoglobin level (Hb) <7 g/dL on 2 occasions, >2 weeks apart (excluding all other contributory causes such as infections)
  • OR
  • Clinical criteria irrespective of hemoglobin level:
    • Hemoglobin > 7 g/dL with any of the following:
      • Facial changes
      • Poor growth
      • Fractures
      • Clinically significant extramedullary hematopoiesis

Treatment options that consider the genetic defect of TDT have the potential to enable patients to live thalassemia-free by eliminating transfusions and maintaining normal, stable Hb levels.1
transfusion therapy icon

MANY PATIENTS WITH TRANSFUSION-DEPENDENT BETA-THALASSEMIA (TDT) EXPERIENCE COMPLICATIONS AND ORGAN DAMAGE DUE TO UNDERLYING DISEASE AND IRON OVERLOAD.1

TIF Guidelines for Transfusion:

Maintaining a Pretransfusion Level of 9-10.5 g/dL1


TIF guidelines for managing hemoglobin levels in transfusion-dependent beta-thalassemia patients
TIF guidelines for managing hemoglobin levels in transfusion-dependent beta-thalassemia patients

Chronic Transfusions Lead to Iron Overload in 
Patients with TDT1

In patients with transfusion-dependent beta-thalassemia, red blood cell transfusions are the main driver for iron overload, which can subsequently lead to multi-organ damage.1,2

In iron overload, transferrin becomes saturated, and iron that is not bound to transferrin (non-transferrin bound iron, or NTBI) accumulates in the plasma. This free iron is highly reactive and generates harmful free radicals, which can damage lipid membranes, organelles, and DNA, causing cell death and fibrosis. The distribution of NTBI and the pattern of tissue iron uptake determine the pattern of organ damage, with myocardial muscle, endocrine tissue, and hepatocytes taking up NTBI rapidly.1

  • Iron tissue uptake occurs mainly in the myocardium, in the liver, in the pancreas, and in other endocrine organs.1
Iron overload in transfusion-dependent beta-thalassemia patients.

Adapted from Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 
3rd ed. Thalassaemia International Federation. 2014.


Transfusions temporarily relieve symptoms of anemia, but do not correct the underlying globin chain imbalance or restore normal erythropoiesis. They also introduce excess iron into the body, necessitating iron chelation therapy.1,4,6,7

Well treated thalassaemia will lead the patient beyond childhood, to an age where there is multiple organ involvement. The consequences, mainly of iron overload, cannot be totally prevented even by present day iron chelation treatment.

—Thalassaemia International Federation Guidelines

Learn how lifelong transfusion therapy may impact quality of life for patients with beta‑thalassemia

Managing and Monitoring Iron Overload in Thalassemia Patients1

The management of iron overload is centered around1

  • Monitoring iron levels
  • Using iron chelating agents

Iron monitoring is key to determining the extent of iron overload and establishing an effective iron chelation regimen in accordance with a patient’s individual needs. Current TIF guidelines recommend several methods to monitor iron levels:1,2,8,9

  • Serum Ferritin (SF) Testing. SF is a widely used method for monitoring iron levels, but may not be the most reliable due to SF level fluctuations.1
  • Liver Iron Concentration (LIC) by MRI and Cardiac Iron Overload by MRI T2*. These are now standard of care and typically performed annually, but could be as frequent as every 6 months in patients with high-risk T2* until levels shift to a lower risk category.2


International guidelines recommend starting iron chelation therapy when patients have received 10 or more transfusions or reached serum ferritin level > 1000 nanograms per milliliter International guidelines recommend starting iron chelation therapy when patients have received 10 or more transfusions or reached serum ferritin level > 1000 nanograms per milliliter

Potential Iron-Induced Complications1,2

Iron Overload Puts TDT Patients At Risk of Multi-Organ Damage2,4

Survival rates and quality of life in patients with beta-thalassemia have drastically improved with iron chelation therapy. However, complications still remain:

Heart Complications

While advances in the last two decades have dramatically reduced the frequency of cardiac complications, the risk of heart failure, left ventricular dysfunction, and arrhythmias remains.1,9

Liver Complications

Iron deposition in the liver can lead to increased ALT and AST, fibrosis, and cirrhosis.1,9 Cirrhosis predisposes patients to a higher risk of hepatocellular carcinoma.1,2 Hepatic disease is becoming a leading cause of mortality as cardiac-related mortality declines due to advances in monitoring and chelation treatment.

Endocrine Complications

These are common and may be difficult to manage. They include hypogonadism (50-60% of patients with thalassemia major); diabetes (14% of transfused thalassemia major patients in North America); hypothyroidism (about 8-10% overall prevalence); hypoparathyroidism; and calcium metabolism abnormalities independent of hypothyroidism, like hypercalciuria (up to 50%) and nephrolithiasis (about 10%).2

Other complications include pain, growth failure, and bone disease.2

Chronic transfusions are associated with additional risks beyond iron overload, including infection, alloimmunity, transfusion-related acute lung injury, and allergic, febrile, and delayed hemolytic reactions.2,10 Owing to technological advances like nucleic acid testing, however, blood safety has improved dramatically in recent years: the risk of contracting a viral infection is now reported to be less than 1 in a million blood transfusions.11

Iron Overload is a Major Issue in TDT12

While effective iron chelation therapy has dramatically improved survival and quality of life in patients with beta‑thalassemia,13,14 complications can still occur, including in the cardiovascular, hepatobiliary, and endocrine systems.12

While chronic transfusion therapy addresses Hb levels transiently, this addresses only the symptoms of TDT. By correcting the genetic defect, there’s potential to eliminate the need for chronic transfusions and reduce the risk of long-term complications.1,2,3

Register now to receive resources to help support your TDT patients, invites to future webinars, and additional information about beta‑thalassemia.

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Consider Asking Your Patients:

"In what ways do RBC transfusions and iron chelation therapy affect your lifestyle today?"

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Take the Beta-Thalassemia Challenge

Patients with transfusion‑dependent beta‑thalassemia (TDT) require lifelong supportive care with regular red blood cell transfusions—typically given every two to five weeks. Which of the following is not true about transfusion therapy?

B.

Chronic transfusion and chelation therapy can help bring hemoglobin levels within the normal range and have improved survival in patients with beta‑thalassemia. However, many patients with TDT experience complications and organ damage due to underlying disease and iron overload, including cirrhosis of the liver.1 Transfusion therapy is life‑long and does not correct the genetic basis of TDT.1,2 Patients with TDT may experience various symptoms of anemia as hemoglobin levels wane between transfusions.1,5

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