What does a low‑normal transferrin level indicate when hemoglobin, ferritin, and liver enzymes are normal, and how should it be managed?

Transferrin of 200 mg/dL with Normal Hemoglobin, Ferritin, and Liver Enzymes

A transferrin level of 200 mg/dL (equivalent to TIBC ~250 mg/dL) falls in the low-normal range and, when accompanied by normal hemoglobin, ferritin, and liver enzymes, most commonly reflects either early nutritional depletion, chronic inflammation with iron sequestration, or a mixed picture requiring transferrin saturation calculation to guide management. 1

Immediate Diagnostic Steps

Calculate transferrin saturation (TSAT) immediately using the formula: (serum iron × 100) ÷ TIBC. 1 This single calculation determines whether you are dealing with:

• TSAT <16–20%: Confirms iron deficiency (absolute or functional) requiring treatment 1
• TSAT 20–45%: Normal iron availability; low-normal transferrin likely reflects nutritional status or inflammation 1
• TSAT ≥45%: Suspect primary iron overload; proceed to HFE genetic testing 1

Measure inflammatory markers (CRP, ESR) concurrently to detect occult inflammation, as ferritin is an acute-phase reactant that can appear falsely normal when inflammation masks underlying iron deficiency. 1

Clinical Interpretation by TSAT Result

If TSAT <20% (Iron Deficiency Despite Normal Ferritin)

This pattern indicates functional iron deficiency or early absolute deficiency with inflammation masking low ferritin. 1

• Ferritin 30–100 μg/L with elevated CRP/ESR represents a mixed picture of true iron deficiency and anemia of chronic disease. 1
• In inflammatory states (IBD, CKD, heart failure), iron deficiency may be present with ferritin levels up to 50–100 μg/L. 1
• Initiate oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or alternate-day dosing to improve absorption by 30–50% and reduce GI side effects). 1
• Expected response: hemoglobin should rise by ≥10 g/L within 2 weeks. 1

Screen for underlying causes:

• Check tissue transglutaminase antibodies for celiac disease (present in 3–5% of iron-deficiency cases). 1
• Test for H. pylori with stool antigen or urea breath test. 1
• In premenopausal women, assess menstrual blood loss history; reserve bidirectional endoscopy for age ≥50 years, GI symptoms, positive celiac/H. pylori tests, or failure to respond after 8–10 weeks. 1

If TSAT 20–45% (Normal Iron Availability)

Low-normal transferrin with normal iron parameters suggests nutritional depletion or chronic inflammation without iron deficiency. 2

• In hemodialysis patients, TIBC (transferrin) directly correlates with nutritional status: values 176–217 mg/dL indicate moderate-to-severe malnutrition. 2
• In decompensated cirrhosis, transferrin <87 mg/dL independently predicts 30-day mortality even after adjusting for organ failure. 3
• Address underlying nutritional or inflammatory conditions rather than supplementing iron. 1

Evaluate for:

• Chronic liver disease (check ALT, AST, albumin, consider abdominal ultrasound). 1
• Chronic kidney disease (check creatinine, eGFR). 1
• Malnutrition (assess dietary intake, weight loss, albumin). 2
• Chronic inflammatory conditions (rheumatologic disease, IBD, chronic infection). 1

If TSAT ≥45% (Suspect Iron Overload)

Order HFE genetic testing for C282Y and H63D mutations immediately. 1 This threshold indicates possible hereditary hemochromatosis or secondary iron overload. 1

• C282Y homozygosity or C282Y/H63D compound heterozygosity confirms HFE-related hemochromatosis. 1
• If ferritin >1,000 μg/L with elevated liver enzymes or platelet count <200,000/μL, consider liver biopsy to assess for cirrhosis. 1
• Do not assume iron overload when TSAT <45%; over 90% of elevated ferritin cases are due to inflammation, liver disease, or metabolic causes. 1

Special Clinical Contexts

Chronic Kidney Disease

In CKD patients, low serum iron with normal TSAT still predicts anemia risk. 4 Patients with normal TSAT (≥20%) but low serum iron (<70 μg/dL in men, <60 μg/dL in women) have 1.56-fold increased odds of anemia compared to those with both normal TSAT and normal iron. 4

• Functional iron deficiency occurs when ferritin 100–700 ng/mL with TSAT <20% despite adequate stores. 1
• In CKD patients on erythropoiesis-stimulating agents, a trial of weekly IV iron (50–125 mg for 8–10 doses) can distinguish functional iron deficiency from inflammatory block. 1

Malnutrition and Chronic Illness

Low transferrin in malnourished dialysis patients may erroneously elevate TSAT, masking true iron deficiency. 2

• TIBC values 176–217 mg/dL correlate with moderate-to-severe malnutrition on subjective global assessment. 2
• Serum ferritin inversely correlates with nutritional status: values 161–363 ng/mL indicate worsening malnutrition. 2
• Transferrin is superior to other laboratory tests in assessing nutrition and supplements clinical assessment. 2

Follow-Up and Monitoring

• Repeat CBC, ferritin, and TSAT at 8–10 weeks after initiating iron therapy to assess response. 1
• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence. 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish stores. 1
• For high-risk groups (menstruating females, vegetarians, athletes), screen ferritin every 6–12 months. 1

Critical Pitfalls to Avoid

• Never interpret transferrin or ferritin in isolation; always calculate TSAT to assess iron availability for erythropoiesis. 1
• Do not assume normal ferritin excludes iron deficiency in inflammatory states; TSAT <16–20% confirms deficiency regardless of ferritin level. 1, 5
• Do not overlook celiac disease screening (3–5% prevalence in iron deficiency), as untreated celiac prevents ferritin recovery. 1
• Recognize that low TIBC in malnourished patients falsely elevates TSAT, potentially masking iron deficiency. 2
• In CKD patients, normal TSAT does not exclude anemia risk when serum iron is low. 4