blood cells blood cells close-up of man

Regular transfusions lead to iron overload Iron overload can lead to multi-organ damage in patients with transfusion-dependent beta (β)-thalassemia (TDT)1,2

Continuous monitoring of iron burden is essential in patients with TDT2,3

In patients with TDT, lifelong regular red blood cell (RBC) transfusions enable survival but lead to iron overload and treatment-related complications.1 The introduction of effective iron chelation therapy has significantly improved survival and quality of life for people living with TDT. However, even present-day chelators cannot completely prevent iron overload.1,3

 

In a 2018-2019 real-world, observational study* of 165 patients with TDT conducted in the UK, a subset of patients exhibited significant iron overload while being managed and monitored in a specialist center. Despite this level of care and utilizing iron chelation therapy, these patients experienced iron overload.4

*This study was funded by bluebird bio, who were involved in study design, interpretation of the data, and the submission of the paper for publication.

The ​​2021 Guidelines for the Management of TDT, published by the Thalassaemia International Federation (TIF), recommend starting iron chelation therapy when patients2:

HAVE RECEIVED THEIR FIRST 10 TO 20 TRANSFUSIONS

OR

HAVE RECEIVED THEIR FIRST
10 TO 20 TRANSFUSIONS

OR

REACHED A SERUM FERRITIN
LEVEL > 1000 ng/mL
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.2,3 The gold standard for assessing iron burden is MRI testing. The Cooley’s Anemia Foundation (CAF) recommends several methods for monitoring iron levels5:
LIC should be measured by MRI when chelation is first initiated and annually thereafter, but every 6 months if on intensive chelation.
Usually not performed until 10 years of age in patients who have started chelation and not exhibited elevated LIC levels for any significant amount of time. Should be measured annually thereafter, but every 6 months if on intensive chelation.
Provide an approximate level of iron overload, but not a reliable indicator of total body and liver or cardiac burden, as ferritin is an acute phase reactant and levels may change for a variety of non-iron-related reasons. Recommended to measure every 1 to 2 months for regularly transfused patient to follow changes and look for consistent trends.
Learn more about the Cooley’s Anemia Foundation guidelines for managing transfusions and monitoring iron overload in your patients with TDT.5,6

Iron tissue uptake can lead to multi-organ damage2

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.2

Liver

 

Increased ALT, AST, fibrosis, cirrhosis7

Hepatic disease is becoming a leading cause of mortality as cardiac-related mortality declines due to advances in monitoring and chelation treatment.

  • Excess iron is primarily stored in the liver and can reach clinically critical levels

Endocrine glands

 

Hypogonadism, hypothyroidism, hypoparathyroidism, diabetes7,8

Endocrine glands can be affected, resulting in conditions such as hypogonadotropic hypogonadism. Growth hormone deficiency can occur despite effective chelation therapy, due to iron deposition in the pituitary gland.

Heart

 

Left ventricular dysfunction, heart failure, arrhythmias7,9

Symptomatic cardiac arrhythmias associated with myocardial iron overload pose significant clinical risk in older patients.

Iron uptake by tissue occurs mainly in the myocardium, liver, pancreas, and other endocrine organs2
Illustration showing the risks iron overload creates in livers, endocrine glands, and heart

ALT = alanine transaminase
AST = aspartate transaminase
NTBI = non-transferrin-bound iron

Adapted from Guidelines for the Management of
Transfusion Dependent Thalassaemia (TDT)
. 4th ed.
Thalassaemia International Federation. 2021.

 

ALT = alanine transaminase
AST = aspartate transaminase
NTBI = non-transferrin-bound iron

Adapted from Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 4th ed. Thalassaemia International Federation. 2021.

ALT = alanine transaminase
AST = aspartate transaminase
NTBI = non-transferrin-bound iron

Adapted from Guidelines for the Management of
Transfusion Dependent Thalassaemia (TDT)
. 4th ed.
Thalassaemia International Federation. 2021.

 

ALT = alanine transaminase
AST = aspartate transaminase
NTBI = non-transferrin-bound iron

Adapted from Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 4th ed. Thalassaemia International Federation. 2021.

 

Transfusions temporarily relieve symptoms of anemia, but are associated with additional risks beyond iron overload

Additional risks include3,10:

  • Infection
  • Alloimmunity
  • Transfusion-related acute lung injury
  • Allergic, febrile, and delayed hemolytic reactions

Because of several technological advances including nucleic acid testing and improved donor selection program, 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

Expert Perspectives: Iron Monitoring and Chelation

Video Thumbnail
Dr. Cappellini discusses the role of iron monitoring and the goals of iron chelation in the treatment of iron overload caused by lifelong transfusion therapy in TDT.