How do you interpret iron studies and manage iron deficiency or overload?

From the Guidelines

Iron studies interpretation and management requires assessment of key markers including serum iron, ferritin, transferrin saturation, and total iron binding capacity, with the goal of improving morbidity, mortality, and quality of life by optimizing iron levels. To interpret iron studies, it's essential to understand the role of each marker:

• Serum iron reflects the amount of iron available for erythropoiesis
• Ferritin reflects iron storage
• Transferrin saturation (TSAT) reflects the percentage of transferrin that is saturated with iron, indicating the amount of iron available for erythropoiesis
• Total iron binding capacity (TIBC) measures the total amount of transferrin available for binding iron.

For iron deficiency, begin with oral iron supplementation, such as ferrous sulfate 325 mg daily or twice daily between meals, providing approximately 65 mg of elemental iron per dose, as recommended by 1. Continue treatment for 3-6 months after hemoglobin normalizes to replenish stores. For patients with intolerance to oral iron, consider alternate day dosing or switching to ferrous gluconate or ferrous fumarate, which may cause less gastrointestinal distress. Intravenous iron (such as iron sucrose, ferric carboxymaltose, or iron dextran) is indicated for malabsorption, severe deficiency, or oral iron intolerance, with the choice of intravenous iron based on its registration for the specific age group or a proven good safety profile, as noted in 1.

Some key points to consider when interpreting iron studies include:

• A TSAT of < 20% and serum ferritin < 100 ng/mL indicate absolute iron deficiency, as defined by 1 and 1
• Functional iron deficiency may occur despite normal or elevated serum ferritin levels, as discussed in 1 and 1
• Serum ferritin levels between 300 and 800 ng/mL are common in dialysis patients and are not associated with adverse iron-mediated effects, as reported in 1

For iron overload, phlebotomy remains first-line therapy for hereditary hemochromatosis, removing one unit of blood weekly until ferritin reaches target levels below 50-100 ng/mL, followed by maintenance phlebotomy, as recommended by 1 and 1. Iron chelation therapy with deferasirox, deferiprone, or deferoxamine is used for transfusional iron overload or when phlebotomy is contraindicated. Monitoring response to therapy requires regular assessment of complete blood count, reticulocyte count, and iron studies, with treatment adjustments based on these parameters, as emphasized in 1. The underlying cause of iron abnormalities should always be investigated, as they often signal other medical conditions requiring specific management.

From the FDA Drug Label

The primary efficacy endpoint was defined as a reduction in LIC of greater than or equal to 3 mg Fe/g dry weight for baseline values greater than or equal to 10 mg Fe/g dry weight, reduction of baseline values between 7 and less than 10 to less than 7 mg Fe/g dry weight, or maintenance or reduction for baseline values less than 7 mg Fe/g dry weight Reduction of LIC and serum ferritin was observed with deferasirox tablet for oral suspension doses of 20 to 30 mg per kg per day.

To interpret iron studies, you need to consider the following key components:

• Iron: measures the amount of iron in the blood
• Ferritin: measures the amount of iron stored in the body
• Iron saturation: measures the percentage of transferrin that is saturated with iron
• Transferrin: a protein that carries iron in the blood
• TIBC (Total Iron-Binding Capacity): measures the total amount of iron that transferrin can carry

Interpretation:

• Iron deficiency: low iron, low ferritin, low iron saturation, high TIBC
• Iron overload: high iron, high ferritin, high iron saturation, low TIBC

Management:

• Iron deficiency: treat with iron supplements
• Iron overload: treat with iron chelators, such as deferasirox, to reduce iron levels 2

From the Research

Interpreting Iron Studies

To interpret iron studies, it's essential to understand the different components, including iron, ferritin, iron saturation, transferrin, and TIBC. Here are the key points to consider:

• Iron: measures the amount of iron in the blood 3
• Ferritin: measures the amount of iron stored in the body, with low levels indicating iron deficiency 4, 5, 3
• Iron saturation: measures the percentage of transferrin that is saturated with iron, with low levels indicating iron deficiency 4, 5
• Transferrin: measures the amount of transferrin in the blood, which binds to iron and transports it throughout the body 4, 5
• TIBC (Total Iron Binding Capacity): measures the amount of transferrin available to bind to iron, with high levels indicating iron deficiency 4, 3

Diagnostic Utility of Iron Studies

The diagnostic utility of iron studies can be summarized as follows:

• Ferritin is the most accurate test for diagnosing iron deficiency, with a sensitivity of 80% and specificity of 99% 3
• Transferrin or TIBC measurement outperforms iron measurement and saturation index in predicting iron deficiency 4
• Serum iron and TIBC give no additional information in the diagnosis of iron deficiency anemia and are redundant if serum ferritin is available 3
• Transferrin saturation and labile plasma iron may be useful in assessing iron overload, particularly in patients with underlying anemias 5

Managing Iron Deficiency or Overload

To manage iron deficiency or overload, the following steps can be taken:

• Iron deficiency: treat with iron supplements, and monitor ferritin levels to ensure adequate iron stores 4, 3
• Iron overload: treat with iron chelation therapy, and monitor transferrin saturation and labile plasma iron to assess response to treatment 5
• Regularly monitor iron studies to prevent iron deficiency or overload, particularly in patients with underlying anemias or other conditions that affect iron metabolism 4, 5, 3