What studies should be ordered when evaluating a patient for possible iron overload from transfusion?

From the Guidelines

When evaluating a patient for possible iron overload from transfusion, the most critical studies to order include serum ferritin, transferrin saturation, and quantitative MRI using T2 or R2 techniques to measure iron concentration in the liver and heart.** These tests are essential for determining the severity of iron overload and guiding chelation therapy decisions. According to the most recent and highest quality study 1, MRI is helpful for detection, non-invasive quantification of iron, and to study the distribution of iron in the liver, spleen, pancreas, heart, and brain in patients with suspicion or diagnosis of iron overload disorder. The study also recommends that R2* sequences are the best validated for quantifying iron. Additionally, the American Society of Hematology 2020 guidelines for sickle cell disease suggest iron overload screening by MRI for liver iron content every 1 to 2 years in patients receiving chronic transfusion therapy 1. Other important tests include a complete blood count (CBC) to assess the degree of anemia, liver function tests to evaluate liver damage, and endocrine function tests to assess the impact of iron overload on endocrine organs. Echocardiography is also useful to evaluate cardiac function, which can be compromised by iron deposition. It is essential to note that serum iron parameters alone are often insufficient to ascertain iron overload, and tissue iron concentrations can be assessed non-invasively by MRI 1. The ESPEN micronutrient guideline also recommends a combination of tests, including plasma iron, transferrin, transferrin saturation, ferritin, CRP, hepcidin, and evaluation of red blood cell morphology for investigating suspected deficiency and overload 1. However, the most recent and highest quality study 1 provides the strongest evidence for the use of MRI in evaluating iron overload. Some key points to consider when ordering these studies include:

• Validated R2, T2*, or R2* methods should be used for MRI, and the same method should be used over time 1.
• If patients are receiving iron chelation, MRI for liver iron content is helpful for titrating iron chelation, regardless of the ferritin level 1.
• Liver biopsy may be considered in select cases for direct measurement of hepatic iron concentration, but it is an invasive procedure.
• Echocardiography is useful to evaluate cardiac function, which can be compromised by iron deposition.
• Endocrine function tests should be ordered as endocrine organs are susceptible to iron toxicity.

From the Research

Evaluating Iron Overload from Transfusion

When evaluating a patient for possible iron overload from transfusion, several studies can be ordered to assess the extent of iron accumulation in the body.

• Serum ferritin levels: This is a helpful and inexpensive guide to relative changes in somatic iron stores 2. However, intersubject variability is quite high, and ferritin values may change disparately from trends in total body iron load over periods of several years.
• Transferrin saturation: This reflects the risk of extrahepatic iron deposition 2 and can be used as a screening tool for iron overload 3.
• Liver iron concentration measurements by MRI: This is recommended annually for all patients on chronic transfusion therapy 2.
• Cardiac T2* by MRI: This should be measured every 6-24 months depending on the clinical risk of cardiac iron deposition 2.
• Computed tomography (CT) scans: CT Hounsfield units in the liver can be used to assess iron overload in the liver 4.
• Liver biopsy: Although invasive and plagued by sampling variability, liver biopsy can be used to estimate liver iron concentration 5, 6.
• Endocrine evaluation: This is important as iron overload can lead to endocrine dysfunction 4, 6.

Laboratory Tests

The following laboratory tests can be ordered to evaluate iron overload:

• Serum ferritin levels
• Transferrin saturation
• Serum iron concentration
• Total iron-binding capacity (TIBC)
• Liver function tests

Imaging Studies

The following imaging studies can be ordered to evaluate iron overload:

• MRI to measure liver iron concentration and cardiac T2*
• CT scans to assess iron overload in the liver

Monitoring

Regular monitoring of serum ferritin levels and liver iron concentration is essential to predict complications of iron overload and to adjust treatment accordingly 2, 6.