Elevated Iron Saturation in Anemia Workup
An iron saturation of 56% as the only abnormality in an anemia workup strongly suggests that iron deficiency is NOT the cause of the anemia, and you should investigate other etiologies including anemia of chronic disease, hemolysis, bone marrow disorders, or other nutritional deficiencies.
Interpretation of the Iron Saturation Value
Iron saturation of 56% indicates adequate to high iron availability for erythropoiesis. 1 The higher the transferrin saturation (TSAT) and serum ferritin, the lower the likelihood that a patient is iron deficient.
This value is well above the threshold for iron deficiency. 1 Absolute iron deficiency in the general population is indicated by a TSAT of less than 16%, while in chronic kidney disease patients, a TSAT < 20% is used as a cutoff.
Your patient's TSAT of 56% essentially rules out iron deficiency as the cause of anemia. 1 The guidelines explicitly state that the higher the TSAT, the lower the likelihood of iron deficiency.
What This Means Clinically
You need to complete the anemia workup with additional studies:
Check serum ferritin to assess total body iron stores and rule out iron overload (ferritin is most accurate when extremely low or extremely high). 1
Obtain complete blood count with indices (MCV, MCH, MCHC) to characterize the anemia as microcytic, normocytic, or macrocytic. 1 The anemia of chronic disease is typically normocytic and normochromic, while microcytosis may reflect hemoglobinopathies or aluminum excess, and macrocytosis suggests B12/folate deficiency.
Measure reticulocyte count (corrected for degree of anemia) to assess bone marrow response. 1 An elevated reticulocyte count suggests hemolysis or acute blood loss.
Screen for chronic inflammatory conditions since anemia of chronic disease can present with low-normal to elevated TSAT when inflammation is present. 1, 2 Inflammatory cytokines (TNF-α, IL-6) cause inadequate erythropoietin production and suppressed erythropoietic response.
Consider checking vitamin B12, folate, and thyroid function as these are easily reversible causes of anemia. 1 Hypothyroidism can cause normochromic, normocytic anemia mimicking erythropoietin deficiency.
Key Differential Considerations
With elevated iron saturation, consider:
Anemia of chronic disease/inflammation: 1, 2 When transferrin saturation is low-normal to elevated and ferritin is high (>300 ng/mL), this suggests inflammatory anemia. However, your patient has high TSAT, making this less typical unless there's concurrent iron overload.
Hemolytic anemia: 1 Check reticulocyte count, LDH, haptoglobin, and indirect bilirubin.
Bone marrow disorders: 1 Abnormal WBC or platelet counts may indicate malignancy or vasculitis affecting marrow function.
Hemochromatosis or iron overload states: High TSAT (>45-50%) can indicate iron overload, especially if ferritin is also markedly elevated.
Sideroblastic anemia: Can present with elevated iron saturation due to ineffective erythropoiesis.
Critical Pitfall to Avoid
Do not give iron supplementation with a TSAT of 56%. 1 Iron therapy is contraindicated when iron stores are adequate or elevated, as it will not correct the anemia and may cause iron overload with associated organ toxicity. The guidelines emphasize that patients with elevated TSAT do not respond to iron therapy with increases in hemoglobin.