From the Guidelines
To evaluate low ferritin in a patient with complex autoimmune disease, I recommend a comprehensive panel including complete blood count (CBC) with differential, comprehensive iron studies (serum iron, total iron binding capacity, transferrin saturation), reticulocyte count, vitamin B12, folate, inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), and specific autoimmune markers relevant to the patient's condition. Additional tests should include thyroid function tests, comprehensive metabolic panel, and stool tests for occult blood. Consider testing for celiac disease with tissue transglutaminase antibodies and total IgA, as autoimmune conditions often cluster together. Hemoglobin electrophoresis may be useful to rule out hemoglobinopathies. The rationale for this comprehensive approach is that ferritin is both an iron storage protein and an acute phase reactant, meaning it can be falsely elevated in inflammatory states despite true iron deficiency. In autoimmune conditions, chronic inflammation can mask iron deficiency, while autoimmune gastritis or celiac disease may cause malabsorption. Occult blood loss should be ruled out as a cause of iron deficiency. This panel will help distinguish between true iron deficiency requiring supplementation and anemia of chronic disease related to the autoimmune condition, as supported by recent guidelines 1. Key laboratory evaluations following IV iron should include a CBC and iron parameters (ferritin, percent transferrin saturation) 4 to 8 weeks after the last infusion, as recommended by expert consensus guidelines 1. In patients with inflammation, a serum ferritin up to 100 mg/L may still be consistent with iron deficiency, and the diagnostic criteria for anemia of chronic disease are a serum ferritin >100 mg/L and transferrin saturation <20% 1. The goal ferritin is 50 ng/mL, regardless of sex at birth, in the absence of inflammation, and soluble transferrin receptor (sTfR) may be useful in evaluating iron status in patients with inflammatory conditions 1. Reticulocyte hemoglobin content (CHr) or reticulocyte hemoglobin equivalent (RET-He) can be used to assess the functional availability of iron to the erythropoietic tissue, as discussed in clinical practice guidelines for evaluation of anemia 1. However, the most recent and highest quality study 1 provides the best guidance for laboratory evaluation and management of iron deficiency in patients with complex autoimmune disease.
From the Research
Evaluating Low Ferritin in Patients with Complex Autoimmune Disease
To evaluate low ferritin in a patient with complex autoimmune disease, several laboratory tests can be considered. The choice of tests depends on the clinical presentation and the need to differentiate between iron deficiency anemia (IDA) and anemia of chronic disease (ACD).
Recommended Laboratory Tests
- Serum ferritin: This is the primary test for evaluating iron stores 2, 3, 4, 5.
- Soluble transferrin receptor (sTfR) assay: This test can help differentiate between IDA and ACD, especially in patients with ferritin levels in the grey zone (10-100 ng/ml) 3, 4.
- Total iron-binding capacity (TIBC) or transferrin concentration: These tests can provide additional information on iron status, but their diagnostic utility is limited compared to serum ferritin and sTfR assay 2, 5.
- Complete blood count (CBC) and reticulocyte count: These tests can help evaluate the severity of anemia and the response to treatment.
- C-reactive protein (CRP) and other inflammatory markers: These tests can help assess the level of inflammation and its impact on iron metabolism.
Considerations for Test Interpretation
- Serum ferritin is an acute phase reactant and can be elevated in patients with chronic inflammation, making it less reliable for diagnosing iron deficiency in these cases 4.
- sTfR assay can provide a more accurate diagnosis of iron deficiency in patients with complex autoimmune disease, especially when ferritin levels are elevated due to inflammation 3, 4.
- Diurnal variation in serum iron and TIBC levels is not significant, and restricting specimen collection to a specific time of day is not necessary 6.