What does low transferrin saturation (TSAT) percent indicate?

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From the Guidelines

A low percent iron saturation indicates that there is insufficient iron bound to transferrin, the protein that transports iron in the bloodstream, suggesting iron deficiency, which can lead to anemia if left untreated, with normal iron saturation ranges from 20-50% and values below 20% indicating iron deficiency 1.

Key Points

  • Iron deficiency occurs when iron stores become depleted, causing reduced hemoglobin production and decreased oxygen delivery to tissues.
  • Symptoms of iron deficiency may include fatigue, weakness, pale skin, and shortness of breath.
  • Treatment usually involves oral iron supplements, such as ferrous sulfate (325 mg), ferrous gluconate (300 mg), or ferrous fumarate (200 mg) taken 1-3 times daily between meals with vitamin C to enhance absorption.
  • Severe cases may require intravenous iron, with laboratory evaluation following IV iron including a CBC and iron parameters (ferritin, percent transferrin saturation (TSAT)) 4 to 8 weeks after the last infusion 1.
  • The underlying cause of iron deficiency should also be identified and addressed, whether it's blood loss, poor dietary intake, or malabsorption.

Diagnosis and Monitoring

  • A TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency, but a ferritin of <100 ng/mL has a low sensitivity of 35%–48% 1.
  • Soluble transferrin receptor (sTfR) has been shown to be more sensitive in patients with inflammatory conditions where the ferritin (but not the TSAT) is unreliable for evaluation of iron deficiency and iron deficiency anemia.
  • Reticulocyte Hb content is a direct assessment of the functional availability of iron to the erythropoietic tissue and can be measured by two methods, the reticulocyte hemoglobin content (CHr) or reticulocyte hemoglobin equivalent (RET-He) 1.

From the Research

Definition of Low Percent Iron Saturation

  • Low percent iron saturation is defined as a transferrin saturation (iron/total iron binding capacity × 100) of less than 20% 2
  • This condition is often associated with iron deficiency anemia, which affects approximately 1.2 billion people worldwide, including 10 million in the US 2

Causes and Risk Factors

  • The most common causes of iron deficiency are bleeding (menstrual, gastrointestinal), impaired iron absorption (atrophic gastritis, celiac disease, bariatric surgical procedures), inadequate dietary iron intake, and pregnancy 2
  • Additional risk factors include use of nonsteroidal anti-inflammatory drugs, inflammatory bowel disease (IBD), and other chronic inflammatory conditions, such as chronic kidney disease (CKD), heart failure (HF), and cancer 2

Diagnosis and Treatment

  • Iron deficiency is diagnosed by low serum ferritin (typically <30 ng/mL) in individuals without inflammatory conditions or by transferrin saturation (iron/total iron binding capacity × 100) less than 20% 2
  • Oral iron supplementation is usually the first line of treatment, but intravenous iron therapy can be used in cases where oral iron is contraindicated or not tolerated 3, 2, 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Intravenous iron supplementation therapy.

Molecular aspects of medicine, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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