Iron deficiency testing
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Iron Deficiency Testing: Key Laboratory Markers and Approaches
Serum Ferritin, Transferrin Saturation, and Red Cell Indices in Iron Deficiency Testing
Serum ferritin is widely recognized as the most useful initial test for detecting iron deficiency, especially in outpatient settings, as it reflects the body’s iron stores. Low ferritin levels are a strong indicator of absolute iron deficiency, but ferritin can be elevated in inflammatory conditions, making interpretation challenging in certain populations such as older adults or those with chronic diseases 147910. Transferrin saturation (TS) and red cell indices, such as mean corpuscular volume (MCV), are also commonly used to assess iron status and the severity of iron-deficient erythropoiesis, but these markers have low specificity and can be affected by other types of anemia, particularly anemia of chronic disease (ACD) 12467.
Advanced and Novel Biomarkers: Soluble Transferrin Receptor, Hepcidin, and Zinc Protoporphyrin
When standard tests are inconclusive, especially in cases where iron deficiency coexists with inflammation or chronic disease, additional biomarkers such as soluble transferrin receptor (sTfR), hepcidin, and zinc protoporphyrin (ZPP) can provide further diagnostic clarity. sTfR is less affected by inflammation and can help distinguish between iron deficiency anemia (IDA) and ACD, while hepcidin, a regulator of iron metabolism, is promising for future routine use but is currently mostly limited to research settings 26789. ZPP is another marker that can be useful in complex cases, though its availability may be limited 26.
Bone Marrow Iron and Special Considerations in Hospitalized or Complex Patients
In hospitalized patients or those with chronic diseases, malignancy, or liver disease, bone marrow iron examination remains the gold standard for diagnosing iron deficiency, as serum markers may be unreliable due to confounding factors like inflammation 14. However, in many cases, serial measurements of serum ferritin can provide similar information and are less invasive 14.
Point-of-Care and Low-Cost Testing Innovations
For low-resource settings, new point-of-care methods such as density-based fractionation of red blood cells using aqueous multiphase systems (AMPS) have shown promise. These tests are rapid, low-cost, and can be performed with minimal equipment, offering sensitivity and specificity comparable to more advanced laboratory methods .
Clinical Context and Diagnostic Strategy
The choice of iron deficiency tests should be guided by the clinical context, including patient age, comorbidities, and the likelihood of concurrent inflammation or chronic disease. In older adults, for example, ferritin cut-offs may need adjustment, and additional tests like sTfR or the sTfR/ferritin index may be helpful . In all cases, a combination of clinical evaluation and laboratory testing is essential for accurate diagnosis 69.
Conclusion
Iron deficiency testing relies on a combination of traditional markers like serum ferritin, transferrin saturation, and red cell indices, with advanced biomarkers such as sTfR and hepcidin providing additional value in complex cases. Bone marrow iron assessment remains the reference standard in challenging scenarios, while innovative point-of-care tests are expanding access in low-resource settings. The optimal diagnostic approach depends on the clinical situation, and integrating multiple tests often yields the most accurate results 12346789+1 MORE.
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