From the Guidelines
High ferritin and elevated IgA levels are significant clinical findings that can indicate several underlying conditions, and the most recent evidence suggests that a ferritin level of 50 ng/mL is the goal, regardless of sex at birth, in the absence of inflammation 1.
Significance of High Ferritin and IgA
High ferritin suggests iron overload or inflammation in the body, as ferritin is an acute phase reactant that increases during inflammatory processes, infections, liver disease, or conditions like hemochromatosis. Elevated IgA (Immunoglobulin A) can indicate mucosal immune system activation, chronic infections, autoimmune disorders like IgA nephropathy, celiac disease, or certain liver diseases.
Possible Conditions
When both markers are elevated simultaneously, this pattern may suggest conditions such as:
- Alcoholic liver disease, where liver inflammation causes increased ferritin while IgA rises due to altered immune function
- Inflammatory bowel disease
- Certain infections
Further Investigation and Treatment
These abnormal values require further investigation through additional blood tests, imaging studies, and possibly tissue biopsies to determine the exact cause. Treatment depends entirely on the underlying diagnosis, ranging from:
- Dietary modifications for celiac disease
- Phlebotomy for hemochromatosis
- Immunosuppressive medications for autoimmune conditions Patients should not attempt to self-treat these laboratory abnormalities without proper medical evaluation, as stated in the most recent guidelines 1.
Key Points to Consider
- Ferritin synthesis is dependent on cellular iron, and even during states of inflammation where absolute iron deficiency is present, the rise in ferritin is blunted 1
- A TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency, but a ferritin of <100 ng/mL has a low sensitivity of 35%–48% 1
- Soluble transferrin receptor (sTfR) has been shown to be more sensitive in patients with inflammatory conditions where the ferritin (but not the TSAT) is unreliable for evaluation of iron deficiency and iron deficiency anemia 1
From the Research
Significance of High Ferritin
- High ferritin levels can indicate iron overload, but it is a non-specific finding and can be caused by various underlying conditions, such as acute phase reactions and reactive increases in ferritin 2, 3
- Hyperferritinemia is frequently overlooked in general practice, and only 10% of cases are related to iron overload, while the rest are due to other conditions 2
- The level of serum ferritin is determined by the underlying conditions to a certain extent, but the variation is significant, and each condition can lead to a wide range of ferritin levels 3
Association with IgA
- There is no direct evidence in the provided studies to suggest a significant association between high ferritin and IgA
- However, it is essential to note that high ferritin levels can be caused by various conditions, including inflammatory and immune-related disorders, which may also affect IgA levels 2, 3
Clinical Implications
- Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex 2
- Deferiprone, an oral iron chelator, has been shown to be effective in reducing iron burden in patients with transfusional iron overload, including those with sickle cell disease and other anemias 4, 5
- The efficacy and safety profiles of deferiprone are acceptable and consistent with those seen in patients with transfusion-dependent thalassemia 5
- Quantitative magnetic resonance imaging can be used to compare the effectiveness of different chelators, such as deferasirox, deferiprone, and desferrioxamine, on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients 6