What causes low iron saturation and normal ferritin
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Causes of Low Iron Saturation and Normal Ferritin
Functional Iron Deficiency: Inflammation and Chronic Disease
One of the primary causes of low iron saturation (TSAT) with normal or high ferritin levels is a condition known as functional iron deficiency. This occurs when the body has sufficient iron stores, as indicated by normal or elevated ferritin levels, but the iron is not readily available for use. This paradoxical situation is often due to inflammation or chronic diseases, which interfere with the body's ability to mobilize and utilize iron effectively 149. Inflammation can elevate ferritin levels because ferritin is an acute-phase reactant, meaning its levels increase in response to inflammation 9.
Hemodialysis and Iron Dysutilization
Patients undergoing hemodialysis frequently exhibit this condition. In these patients, the combination of high ferritin and low TSAT is often linked to inflammation and the body's impaired ability to use iron for erythropoiesis (the production of red blood cells) 137. Studies have shown that hemodialysis patients with low TSAT and high ferritin levels are at an increased risk of cardiovascular and cerebrovascular diseases, as well as higher mortality rates 7.
Diagnostic Challenges and Inflammatory Markers
The diagnostic challenge in these cases lies in distinguishing between iron deficiency and inflammation. Elevated ferritin levels can mask iron deficiency because ferritin is also a marker of inflammation. Therefore, additional markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are often used to assess the inflammatory status and help differentiate between iron deficiency and inflammation 9.
Iron Metabolism in Older Adults
In older adults, the prevalence of functional iron deficiency is higher due to the increased incidence of chronic inflammatory conditions. This demographic often shows high ferritin levels with low TSAT, complicating the diagnosis and management of iron deficiency 5. The presence of multiple comorbidities in older adults further exacerbates this issue, making it crucial to use a comprehensive set of biomarkers for accurate diagnosis.
Implications for Treatment
The treatment of patients with high ferritin and low TSAT is complex. While iron supplementation is a common approach, it must be administered cautiously, especially in the presence of inflammation. Intravenous iron has been shown to be effective in increasing hemoglobin levels in anemic hemodialysis patients, but its long-term safety remains uncertain 3. The goal is to improve iron availability without exacerbating inflammation or causing iron overload.
Conclusion
Low iron saturation with normal or high ferritin levels is primarily caused by functional iron deficiency, often due to inflammation or chronic disease. This condition is particularly prevalent in hemodialysis patients and older adults. Accurate diagnosis requires a combination of iron status markers and inflammatory markers. Treatment strategies must be carefully tailored to address both iron deficiency and underlying inflammation to improve patient outcomes.
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Most relevant research papers on this topic
#6917 IMPACT OF FUNCTIONAL IRON DEFICIENCY IN NON-ANEMIC HEMODIALYSIS PATIENT ON NEUROCOGNITIVE AND QUALITY OF LIFE: A SINGLE CENTER CROSS-SECTION STUDY
Functional iron deficiency in non-anemic hemodialysis patients can negatively impact neurocognitive function and quality of life, highlighting the need for iron supplementation in these patients.
Ferritin in the Serum of Normal Subjects and Patients with Iron Deficiency and Iron Overload
Ferritin levels in serum are a quantitative measure of storage iron in normal subjects and those with iron deficiency or overload.
Highly CitedFerric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study.
Intravenous ferric gluconate is highly effective in anemic hemodialysis patients with high ferritin and low transferrin saturation, improving hemoglobin levels and reducing iron deficiency.
RCTHighly CitedInvestigation and management of a raised serum ferritin
Raised serum ferritin levels can be due to various causes, including iron overload, inflammation, liver or renal disease, malignancy, and metabolic syndrome.
Highly CitedIron in the General Population and Specificities in Older Adults: Metabolism, Causes and Consequences of Decrease or Overload, and Biological Assessment
Older adults have a high frequency of iron deficiency and severe consequences, making accurate diagnosis and treatment decisions crucial.
Very Rigorous JournalDiagnosis of iron deficiency anemia in a rural population of children. Relative usefulness of serum ferritin, red cell protoporphyrin, red cell indices, and transferrin saturation determinations.
Serum ferritin is a useful diagnostic tool for iron deficiency anemia in children, but other, less expensive methods are more effective in identifying anemic iron-deficient patients.
Observational StudyLow transferrin saturation (TSAT) and high ferritin levels are significant predictors for cerebrovascular and cardiovascular disease and death in maintenance hemodialysis patients
Low transferrin saturation levels in maintenance hemodialysis patients increase the risk of cerebrovascular and cardiovascular disease and death, while high ferritin and low TSAT levels have a lower risk.
Observational Study
Rigorous JournalDecreased lung function is associated with elevated ferritin but not iron or transferrin saturation in 42,927 healthy Korean men: A cross-sectional study
Hyperferritinemia is associated with decreased lung function in healthy Korean men, but not with iron or transferrin saturation.
Observational StudyRigorous JournalCombined high serum ferritin and low iron saturation in hemodialysis patients: the role of inflammation.
In maintenance hemodialysis patients, high serum ferritin levels, especially when combined with low iron saturation, are associated with inflammation.
Observational StudyHighly CitedAssessing iron status: beyond serum ferritin and transferrin saturation.
Newer markers for iron status, such as reticulocyte hemoglobin content and soluble transferrin receptor, may be useful in diagnosing iron deficiency in chronic kidney disease patients.
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