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Transfusion Therapy Chronic RBC Transfusions Are Central to the Treatment of TDT1

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

Current guidelines from the Thalassaemia International Federation (TIF) recommend that transfusions be given every 2 to 5 weeks to correct anaemia, suppress ineffective erythropoiesis, and enable survival. An additional goal of transfusion therapy is the inhibition of iron absorption, which occurs in non-transfused patients as a consequence of increased (though ineffective) erythropoiesis.1,4

According to current TIF guidelines, regular transfusions should be considered in patients with Hb <7 g/dL on two occasions, >2 weeks apart; or in patients with Hb >7 g/dL who have other clinical symptoms like facial changes, poor growth, fractures, or clinically significant extramedullary haematopoiesis.1

TIF Guidelines for Transfusion:

Maintaining a Pretransfusion Level of 9-10.5 g/dL1


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TIF guidelines for transfusions, maintaining haemoglobin levels of 9-10 g/dL (grams per deciliter)

Chronic Transfusions Lead to Iron Overload in 
Patients With TDT1

In patients with TDT, 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
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Diagram of organs affected by iron overload including; liver, pancreas, and other endocrine organs.

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


Transfusions temporarily relieve symptoms of anaemia, but do not address 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

Managing and Monitoring Iron Overload1

The management of iron overload is centred 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


Start iron chelation therapy if you have received 10 or more transfusions or reached serum ferritin level > 1000 nanograms per milliliter transfusion therapy icon

Potential Complications in β-Thalassaemia Patients Receiving 
Transfusion Therapy2,4

Chronic transfusion therapy, while effective, can lead to a range of complications.

  • Cardiac Complications. In birth cohorts of patients before 1980, cardiac deposition of iron was associated with death in the second or third decade of life. While advances in the last two decades have dramatically reduced the frequency of cardiac complications, the risk remains.2,3
  • Liver Complications. Iron deposition in the liver can lead to cirrhosis, which predisposes patients to a higher risk of hepatocellular carcinoma.1,2
  • Endocrine Complications. These are common and difficult to manage. They include hypogonadism (50-60% of patients with thalassaemia major); diabetes (14% of transfused thalassaemia 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

Iron-Induced Complications1,2


List of common iron-Induced Complications in the heart, liver, and endocrine glands List of common iron-Induced Complications in the heart, liver, and endocrine glands
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

The advent of effective iron chelation therapy has dramatically improved survival and quality of life in patients with β‑thalassaemia.13,14 However, challenges remain.12
  • Myocardial and hepatic iron overload can occur.12
  • Symptomatic cardiac arrhythmias associated with myocardial iron overload can pose significant clinical risk in older patients.13
  • Hepatic disease is becoming a leading cause of mortality as cardiac-related mortality declines due to advances in monitoring and chelation treatment.13
  • Hypogonadotropic hypogonadism and growth hormone deficiency can occur despite chelation therapy, due to iron deposition in the pituitary gland.14
Chronic transfusion therapy enables survival, but does not treat the underlying genetic cause.1

Take the β-Thalassaemia Challenge

Despite significant improvements in the survival of β-thalassaemia patients receiving transfusion and chelation therapy, the risk of cardiac-related mortality in men aged 30-39 has been reported to be:

D.

A historical prospective study of 1044 Greek patients with transfusion-dependent β-thalassaemia found significantly improved mortality rates from 1990-1999 to 2000-2008 in people aged 20 to 40 compared to the general population (standard mortality ratios 28.9 and 13.5, respectively). However, mortality remained increased relative to the general population; in males aged 30-39, the risk of cardiac-related death was 57.4 times greater than in the general population.3

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