What is the easiest way to interpret iron studies?

Easiest Way to Interpret Iron Studies

Start with transferrin saturation and ferritin together—these two tests provide the most straightforward assessment of iron status, with transferrin saturation <20% plus ferritin <30 ng/mL confirming iron deficiency in most patients. 1, 2

Step-by-Step Interpretation Algorithm

Step 1: Check Transferrin Saturation First

• Transferrin saturation (TSAT) = (Serum Iron ÷ TIBC) × 100 3
• TSAT <20% suggests iron deficiency and indicates insufficient iron available for red blood cell production 1, 2
• TSAT >55% suggests iron overload and warrants further evaluation 1
• TSAT reflects iron immediately available to bone marrow for hemoglobin synthesis 4

Step 2: Interpret Ferritin Based on Clinical Context

• In patients WITHOUT inflammation: Ferritin <30 ng/mL confirms iron deficiency 1, 2
• In patients WITH chronic inflammation (CKD, heart failure, inflammatory conditions): Use ferritin <100 ng/mL as the threshold for iron deficiency 1, 3
• Ferritin >200 ng/mL (women) or >300 ng/mL (men) suggests iron overload 1
• Ferritin is the single best biomarker for assessing tissue iron stores 4, 5

Step 3: Recognize the Pattern

Iron Deficiency Pattern:

• Low ferritin (<30 ng/mL without inflammation, <100 ng/mL with inflammation) 1, 3
• Low TSAT (<20%) 1, 2
• Elevated TIBC (>400 μg/dL typically) 3
• Low serum iron 1

Iron Overload Pattern:

• Elevated ferritin (>200 ng/mL women, >300 ng/mL men) 1
• Elevated TSAT (>55%) 1
• Normal or low TIBC 3
• Elevated serum iron 1

Normal Iron Status:

• Ferritin 30-200 ng/mL (women) or 30-300 ng/mL (men) 1
• TSAT 20-55% 1

Critical Pitfalls to Avoid

Ferritin is an Acute Phase Reactant

• Ferritin rises with inflammation, infection, liver disease, and malignancy regardless of actual iron stores 4, 1
• In dialysis patients, ferritin interpretation is particularly difficult because it's often elevated independent of iron stores 4
• Consider checking C-reactive protein to assess for inflammation when ferritin seems discordant with other findings 4

Don't Rely on Hemoglobin Alone

• Hemoglobin and hematocrit are late indicators of iron deficiency—iron stores must be completely depleted before anemia develops 1
• Many patients have symptomatic iron deficiency (fatigue, restless legs, exercise intolerance) without anemia 2

TSAT Has Day-to-Day Variability

• TSAT varies with meals, time of day, and inflammation 3
• Obtain fasting samples when possible for most accurate assessment 4
• Day-to-day variation is greater for TSAT than for hemoglobin 3

Special Population Adjustments

Chronic Kidney Disease Patients

• Use ferritin <100 ng/mL as threshold for iron deficiency 1
• TSAT may be more reliable than ferritin in CKD because it's less affected by inflammation 4
• Ferritin <25 ng/mL (males) or <11 ng/mL (females) predicts insufficient iron stores in non-dialysis CKD 4

Screening for Hemochromatosis

• Fasting TSAT >45% plus elevated ferritin warrants genetic testing for HFE mutations 4
• Ferritin >1,000 ng/mL in confirmed hemochromatosis predicts cirrhosis risk 4

Pregnant Women

• Lower ferritin thresholds apply—consider iron deficiency at ferritin <30 ng/mL 2
• Up to 84% of third-trimester pregnant women have iron deficiency 2

When Standard Tests Are Inconclusive

• Consider soluble transferrin receptor (sTfR) when ferritin is elevated due to inflammation but iron deficiency is still suspected 6
• Elevated sTfR indicates iron deficiency even when ferritin is normal or high due to inflammation 6
• MRI T2* is the gold standard for non-invasive assessment of liver iron content in suspected iron overload 1

Practical Clinical Approach

For most patients, this simple rule works: If TSAT <20% AND ferritin <30 ng/mL (or <100 ng/mL if inflammation present), diagnose iron deficiency and investigate the cause 1, 3, 2. The combination of these two tests has sensitivity of 79% and specificity of 98% at the 30 μg/L ferritin threshold 7.