Chemistry, toxicology & urinalysis

General chemistry

Metabolism

Transferrin



Last author update: 15 November 2023
Last staff update: 22 January 2024

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PubMed Search: Transferrin

David F. Haddock, M.D.
Yusheng Zhu, Ph.D.
Page views in 2023: 109
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Cite this page: Haddock DF, Zhu Y. Transferrin. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/chemistrytransferrin.html. Accessed April 29th, 2024.
Definition / general
  • Glycoprotein responsible for storage and transport of iron in serum
Essential features
  • Delivers iron to marrow for heme synthesis and transfers iron to all tissues for absorption, utilization and storage
  • Used to calculate total iron binding capacity (TIBC) and iron saturation; in patients with iron deficiency, the degree of transferrin saturation is an extremely sensitive indicator of functional iron depletion
  • Scavenger of free toxic iron; in screening for hereditary hemochromatosis, transferrin saturation provides a better indication of the homozygous genotype than does ferritin
  • Negative acute phase reactant (Int J Infect Dis 2022;116:74)
  • Can sequester iron to prevent acquisition by pathogenic bacteria (Coord Chem Rev 2021;449:214186)
Terminology
  • Iron binding component
  • Serotransferrin
  • Siderophilin
  • β1 metal binding globulin
  • β2 transferrin: specific to cerebrospinal fluid and perilymph fluid of the inner ear; useful for diagnosing cerebrospinal fluid (CSF) leak (Int Forum Allergy Rhinol 2016;6:8)
ICD coding
  • Not applicable unless the diagnosis relates to iron deficiency / disorders
Pathophysiology
  • Transferrin (Tf) is a 687 amino acid glycoprotein, which is the major β globulin in serum; it is synthesized in the liver in response to acute decreases in the concentration of circulating iron
  • Unbound form of the molecule apotransferrin has 2 binding sites for free iron (Fe3+), which binds either monoferrically or diferrically (when iron is abundant)
  • Receptor for transferrin (TfR) is found on most cells and endocytoses in the transferrin / iron complex (Medicines (Basel) 2019;6:85)
  • Transferrin binds and transports ferric iron stored by ferritin from intracellular and mucosal sources for delivery to bone marrow for heme synthesis and transfers iron to all tissues for absorption, utilization and storage
  • Proportional to TIBC
  • In iron deficient anemia, transferrin is expected to be elevated
  • Liver disease, inflammatory states, thalassemia and conditions that cause iron overload usually result in a decrease in transferrin
  • Physiologically normal decrease in iron concentration with a concurrent elevation of transferrin should be expected during pregnancy
  • Chronic saturation of transferrin occurs in hemochromatosis (hereditary and idiopathic) and transfusional hemosiderosis; chronic saturation of transferrin results in reduced iron binding capacity, hence iron is not excreted normally and deposits in tissue (Trends Pharmacol Sci 2021;42:640)
  • Transferrin also plays a role in regulation of other metals in human serum, such as Ti(IV), Co(III), Ga(III), Cr(III) and Zn(II) (Coord Chem Rev 2021;449:214186)
Test indications
  • As a transport protein of iron in the blood, transferrin is a measure of iron binding capacity
  • Useful in the diagnosis of disorders of iron metabolism as a component of an iron panel, including iron saturation, serum ferritin and TIBC
Laboratory
  • Assays
    • Nephelometry
    • Turbidimetry
  • Preanalytical factors
    • Multiple situations may alter the transferrin level and total iron binding capacity
    • Confounding factors, such as medications (chloramphenicol reduces transferrin receptor expression), iron supplements and iron fortified multivitamins, recent transfusion or recent ingestion of a high iron meal (J Cell Physiol 1999;180:334)
    • Iron contamination due to oral ingestion or other administration should be avoided
    • Transferrin is usually ordered as part of an iron study; therefore, the specimen requirements are similar
    • Fasting serum in the morning is preferred, utilizing a serum or heparinized plasma tube (red or green top)
    • Serum separator tube, such as gold topped tube, containing clot activator and gel
    • Containers with EDTA are not acceptable as EDTA binds metal ions with high affinity; similarly, oxalate and citrate have lower pH and will bind ferric iron
  • Typical reference range: 2.0 - 3.6 g/L
Interpretation
  • Causes of high transferrin
    • Iron deficiency
  • Causes of low transferrin
    • Liver diseases
    • Anemia of chronic disease
    • Kidney insult or injury
    • Infection and acute phase reaction
    • Malignancy
    • Atransferrinemia due to transferrin gene mutation
    • Iron overload such as hemochromatosis (Trends Pharmacol Sci 2021;42:640)
Board review style question #1
A 17 year old unrestrained male passenger of a motor vehicle accident arrived at the emergency department with multiple fractures of the bilateral upper and lower extremities, hematomas and contusions. The patient exhibited signs of confusion and lethargy. The presence of nonpurulent serous drainage from the nose was concerning as it could indicate a cerebrospinal fluid leak from a suspected cranial trauma. What is the most specific test to determine the source of the rhinorrhea?

  1. β2 transferrin
  2. β trace protein
  3. Glucose
  4. Radionuclide cisternography
  5. Ring sign
Board review style answer #1
A. β2 transferrin. β2 transferrin is a transferrin variant found in cerebrospinal fluid (CSF), perilymph of the ear and vitreous humor of the eye. It is a highly specific marker for CSF. Answer D is incorrect because radionucleotide cisternography is very specific for identifying a CSF leak; however, it cannot distinguish between a rhinologic versus an otologic source. Answer B is incorrect because β trace protein, although shown in some studies to rival β2 transferrin in specificity and sensitivity, is also present in blood. In certain patient groups, β trace protein is decreased and should not be used. Answer E is incorrect because ring sign is a visible halo sometimes found at the bedside of patients with bloodstains mixed with CSF. It has poor specificity for CSF detection. Answer C is incorrect because although the use of glucose testing strips on rhinorrhea specimens was once thought to be a positive indication of the presence of CSF, studies have shown that glucose can be detected in otherwise healthy patients. The detection of glucose in rhinorrhea is not considered sensitive or specific for CSF (Int Forum Allergy Rhinol 2016;6:8).

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Reference: Transferrin
Board review style question #2
An 18 year old woman with past medical history of sickle cell trait, iron deficiency and neutropenia presents to the office for follow up. She states that she has been having right lower quadrant pain for the past week. The pain can become so severe that she rates it at 7/10. It causes nausea and abdominal fullness. She denies fever, colicky pain or flank pain. The patient serum transferrin concentration is 390 mg/dL (normal: 200 mg/dL to 360 mg/dL). Which of the following is most likely observed in this patient?

  1. Ferritin concentration of 10 ng/mL
  2. Ferritin concentration of 200 ng/mL
  3. Iron concentration of 100 μg/dL
  4. Iron saturation 80%
  5. Total iron binding capacity of 200 μg/dL
Board review style answer #2
A. Ferritin concentration of 10 ng/mL. Understanding the normal ranges for transferrin, iron saturation, iron concentration and TIBC will demonstrate that normal ferritin concentration in women is 24 to 307 ng/mL. The patient has a history of anemia and presents with an elevated transferrin; therefore, the ferritin concentration should be decreased. Answers B, C, D and E are incorrect because these responses are consistent with normal iron levels.

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Reference: Transferrin
Board review style question #3
Hypertransferrinemia can be seen in patients with

  1. Acute myocardial infarction
  2. Cirrhosis
  3. Hypoalbuminemia
  4. Iron deficiency
  5. Nephrotic syndrome
Board review style answer #3
D. Iron deficiency. Iron deficiency is the only option that is compatible with an elevated transferrin level. Answer C is incorrect because hypotransferrinemia usually accompanies hypoalbuminemia and is also an indication of protein malnutrition. Answer E is incorrect because nephrotic syndrome causes loss of proteins such as transferrin. Answer B is incorrect because cirrhosis results in decreased production of all proteins synthesized in the liver. Answer A is incorrect because hypotransferrinemia is associated with acute myocardial infarction rather than normal or excess transferrin. Transferrin is also a negative acute phase reactant and would be decreased in the hours and days following an acute event such as an infarction.

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Reference: Transferrin
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