What does a low serum transferrin level of 189 indicate and how is it treated?

Low Serum Transferrin (189 mg/dL): Clinical Significance and Management

What This Value Indicates

A serum transferrin level of 189 mg/dL is mildly to moderately low and most commonly reflects chronic inflammation, malnutrition, or liver disease rather than iron deficiency. 1

Normal Reference Range Context

• Normal transferrin typically ranges from 200-360 mg/dL, making 189 mg/dL slightly below the lower limit of normal. 1
• This level may be considered low-normal or mildly decreased depending on your laboratory's specific reference range. 1

Primary Causes to Consider

Transferrin is a negative acute-phase reactant, meaning it decreases during inflammation, infection, or malignancy independent of iron status. 1 The key diagnostic task is determining whether this reflects:

1. Chronic inflammation/disease (most common)

   • Inflammatory bowel disease, heart failure, chronic kidney disease, or active infection 1
   • Inflammatory cytokines (TNF-α, IL-6) suppress transferrin synthesis 1

2. Protein-energy malnutrition

   • Reduced hepatic synthesis due to inadequate protein intake 1

3. Liver disease

   • Impaired synthetic function 1

4. Rare genetic conditions

   • Hereditary hypotransferrinemia (extremely rare, typically presents with severe anemia in childhood) 2, 3

Critical Diagnostic Algorithm

Step 1: Calculate Transferrin Saturation (TSAT)

You must calculate TSAT to interpret iron status accurately. 4

• Formula: TSAT (%) = (serum iron / TIBC) × 100 4
• Convert transferrin to TIBC: TIBC (μmol/L) = Transferrin (g/L) × 25.1 4

Step 2: Evaluate Ferritin Alongside Transferrin

Never interpret transferrin in isolation—ferritin is essential to distinguish iron deficiency from inflammation. 1

The pattern determines the diagnosis:

Pattern	TSAT	Ferritin	Interpretation
Iron deficiency	<16-20%	<30-50 ng/mL	True iron deficiency [4,1]
Anemia of chronic disease	<20%	>100-300 ng/mL	Inflammation, not iron deficiency [1]
Functional iron deficiency	<20%	100-300 ng/mL	Iron trapped in stores, unavailable for erythropoiesis [4]

Step 3: Check Inflammatory Markers

• Obtain CRP and ESR to identify inflammatory states that confound interpretation. 1
• In inflammatory conditions, ferritin rises as an acute-phase reactant while transferrin falls, masking true iron status. 1

Treatment Approach

If Iron Deficiency is Confirmed (Low Ferritin + Low TSAT)

Treat with iron supplementation:

• Oral iron is first-line in uncomplicated cases 2
• IV iron is preferred in chronic inflammatory conditions (heart failure, CKD, IBD) where oral absorption is impaired by hepcidin activation 4
• Target TSAT ≥20% to ensure adequate iron for erythropoiesis 4
• Recheck iron parameters 4-8 weeks after IV iron (not sooner, as circulating iron interferes with assays) 4

If Anemia of Chronic Disease (High Ferritin + Low TSAT)

Address the underlying inflammatory condition first:

• Low transferrin reflects inflammation, not iron deficiency 1
• Iron supplementation is generally not indicated unless functional iron deficiency is present 4
• In functional iron deficiency (ferritin 100-300 ng/mL with TSAT <20%), IV iron may improve erythropoiesis despite "adequate" stores 4

If Malnutrition is Suspected

Nutritional assessment and protein repletion:

• Use serum albumin and prealbumin for nutritional assessment rather than transferrin in chronic disease states 1
• Transferrin has limited utility in chronic kidney disease patients on dialysis due to confounding from chronic blood loss and erythropoietin therapy 1

Critical Pitfalls to Avoid

1. Do not assume low transferrin equals iron deficiency. In inflammatory conditions, ferritin rises while transferrin falls, creating a misleading picture. 1

2. Do not evaluate iron parameters within 4 weeks of IV iron administration due to assay interference. 4, 1

3. Do not rely on transferrin alone in chronic disease. Transferrin is a poor marker of nutritional status in inflammatory conditions, heart failure, or CKD. 1

4. Do not ignore clinical context. A transferrin of 189 mg/dL in a patient with active inflammation is expected and does not require treatment, whereas the same value in a healthy individual warrants further investigation. 1

5. Do not miss functional iron deficiency. Patients with chronic disease can have normal or elevated ferritin but still require iron supplementation if TSAT <20%. 4

Monitoring Strategy

• Recheck transferrin, ferritin, TSAT, and CBC after addressing the underlying cause (inflammation, malnutrition, or iron deficiency) 4
• In chronic inflammatory conditions, transferrin may remain low despite adequate treatment—focus on TSAT and ferritin trends instead 1
• If treating with IV iron, wait 4-8 weeks before rechecking iron parameters to allow accurate assessment 4