What is transferring saturation in a medical context?

What is Transferrin Saturation?

Transferrin saturation (TSAT) is a laboratory measure that represents the ratio of serum iron to total iron-binding capacity (TIBC), expressed as a percentage, and serves as a key indicator of iron availability in the bloodstream for erythropoiesis and cellular metabolism. 1

Calculation and Measurement

• TSAT is calculated as: (serum iron ÷ total iron-binding capacity) × 100 1
• In most laboratories, TIBC is not directly measured but is derived from serum transferrin concentration after correction by a constant value (mg of transferrin multiplied by 1.24 or 1.25), which necessitates standardization among laboratories 1
• The test reflects the percentage of transferrin molecules that are saturated with iron at the time of measurement 1

Clinical Significance

Iron Deficiency Assessment

• TSAT <20% typically indicates iron deficiency and insufficient iron availability for red blood cell production 1
• In chronic kidney disease patients on erythropoiesis-stimulating agents (ESAs), maintaining TSAT >20% improves anemia correction and reduces ESA requirements 1
• TSAT values <16% are commonly used as a diagnostic threshold for iron deficiency anemia 2

Iron Overload Detection

• TSAT >50-55% suggests iron overload and increased risk of iron deposition in tissues 1
• In hereditary hemochromatosis screening, elevated TSAT (>45-50% in men, >60% in women) serves as a primary screening parameter 1
• Persistently elevated TSAT >50% has been associated with increased all-cause mortality (hazard ratio 1.60) 1

Advantages Over Ferritin

TSAT provides a more accurate assessment of immediately available iron for biological processes compared to ferritin, particularly in inflammatory states. 3, 4

• Unlike ferritin, TSAT is not an acute-phase reactant and is less affected by inflammation, infection, or chronic disease 3
• In heart failure with preserved ejection fraction (HFpEF), TSAT correlates with peak oxygen consumption, exercise hemodynamics, and clinical outcomes, whereas ferritin does not 4
• TSAT better predicts metabolic and hemodynamic exercise responses than ferritin in patients with cardiac dysfunction 4

Important Limitations and Caveats

• TSAT exhibits significant daily and day-to-day variability, particularly influenced by inflammation, which limits its reliability as a standalone measure 1
• Blood transfusion causes a significant rise in TSAT that persists for 24-36 hours; therefore, iron studies should be obtained before transfusion when possible 2
• In chronic kidney disease patients with inflammation, the scenario of high ferritin (>800 ng/mL) with low TSAT (<20%) has become increasingly common, reflecting impaired iron mobilization from reticuloendothelial stores 3
• TSAT ≥20% does not exclude bone marrow iron deficiency, as several studies have demonstrated absent bone marrow iron despite TSAT values above this threshold 1

Optimal Target Ranges

General Population

• The optimal TSAT range associated with lowest mortality is 24-40% 5
• Both low (<17.5%) and high (>31.3%) TSAT values are independently associated with increased total and cardiovascular mortality in a J-shaped pattern 5

Chronic Kidney Disease

• For hemodialysis patients receiving ESAs, maintaining TSAT >20-30% reduces ESA requirements and improves hemoglobin response 1
• Higher TSAT targets (30-50%) allow hemoglobin maintenance at lower ESA doses compared to lower targets (20-30%) 1

Hemochromatosis Monitoring

• In patients with hemochromatosis, TSAT may remain elevated (>50%) even when serum ferritin is within target range (<50 μg/L), and prolonged exposure to elevated TSAT may contribute to joint symptoms regardless of ferritin levels 1