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Anti-Prothrombin IgG
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Anti-Prothrombin IgG

Prothrombin is a vital protein in the blood clotting process, playing a key role in the conversion of fibrinogen to fibrin to help form blood clots. 

Anti-prothrombin IgG is an autoimmune antibody that targets prothrombin. It disrupts normal clotting and increases the risk of conditions such as antiphospholipid syndrome (APS), which can lead to blood clots, strokes, and pregnancy complications.

What is Prothrombin?

Prothrombin (Factor II) is an important protein in blood clotting. It is made in the liver and flows through the bloodstream in its inactive form. 

When a blood vessel is injured, prothrombin is converted into thrombin, an enzyme that plays a key role in forming blood clots. Thrombin helps turn fibrinogen into fibrin, which forms a mesh that strengthens the clot and helps stop the bleeding.

Prothrombin's proper function is essential for maintaining balance in the body’s clotting system. If prothrombin is too active, it can cause too many clots (thrombosis), while if it is not active enough, it can lead to uncontrolled bleeding. 

What is Anti-Prothrombin IgG?

When the immune system mistakenly targets prothrombin, it produces autoantibodies—specifically anti-prothrombin IgG. These autoantibodies can interfere with the clotting process, increasing the risk of abnormal clot formation or bleeding.

Anti-prothrombin IgG is commonly associated with antiphospholipid syndrome (APS), an autoimmune disorder that increases the risk of blood clots, stroke, and pregnancy complications. 

While anti-prothrombin IgG can signal the possibility of APS, a positive result alone does not confirm the diagnosis. Further clinical investigation and additional testing are required to make an accurate diagnosis.

Anti-Prothrombin IgG: Its Role in Autoimmune Disorders

Anti-prothrombin IgG is an autoimmune marker that targets prothrombin, disrupting the normal blood clotting cascade. In APS, the immune system mistakenly produces these antibodies, increasing the risk of thrombosis (blood clot formation) and complications such as recurrent miscarriages or stroke, especially in younger individuals. 

Although anti-prothrombin IgG is a significant biomarker for APS, its presence alone is not sufficient for diagnosis. It must be interpreted alongside clinical symptoms and other antiphospholipid antibodies, such as anticardiolipin and anti-beta-2 glycoprotein I antibodies.

Who Should Get Anti-Prothrombin IgG Tested?

Anti-prothrombin IgG testing is typically recommended for patients exhibiting signs of APS or other clotting disorders. Symptoms that may prompt testing include:

  • Unexplained blood clots, particularly in unusual locations (e.g., brain, lungs, or veins in the legs)
  • Recurrent miscarriages or pregnancy complications, such as preeclampsia or stillbirth
  • Thrombocytopenia (low platelet count), which can be seen in 15-25% of APS patients
  • Livedo reticularis (a lace-like rash)
  • Stroke or transient ischemic attack (TIA), particularly in younger patients

Additionally, patients with autoimmune conditions like systemic lupus erythematosus (SLE) are at higher risk of developing APS, and anti-prothrombin IgG testing may be part of their evaluation.

Test Procedure and Interpretation

The following section outlines testing procedures, requirements, and interpretation: 

Testing Procedure and Preparation Requirements

A routine blood draw is required, with no special preparation needed from the patient. Testing is typically done using enzyme-linked immunosorbent assays (ELISA), which can quantify their presence.

Normal Reference Ranges

Anti-prothrombin IgG levels vary depending on the laboratory, but normal levels are generally considered absent or very low

Clinical Implications of Elevated Levels

Elevated anti-prothrombin IgG levels are commonly linked to APS, a condition that significantly increases the risk of blood clots, pregnancy complications, and strokes. 

However, a positive result alone does not confirm APS, and additional tests (e.g., anticardiolipin, anti-beta-2 glycoprotein I, and lupus anticoagulants) and clinical symptoms are needed for a definitive diagnosis.

Clinical Implications of Decreased Levels

Low or negative anti-prothrombin IgG levels suggest that these antibodies are not contributing to the patient's symptoms. However, it is important to note that a negative result does not completely rule out APS, especially if other clinical features are present.

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See References

Antiprothrombin Antibodies. LabCorp Test Master Test Account, 504439. FINAL REPORT. (n.d.). Retrieved February 8, 2025, from https://files.labcorp.com/testmenu-d8/sample_reports/504439.pdf

‌Arcilla CK, Zubair M. Antiphospholipid Antibody Testing. [Updated 2024 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK603749/

Bustamante JG, Goyal A, Rout P, et al. Antiphospholipid Syndrome. [Updated 2024 May 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430980/

Hwang, K.-K., Grossman, J. M., Sudha Visvanathan, Chukwuocha, R. U., Woods, V. L., Le, D., Hahn, B. H., & Chen, P. P. (2001). Identification of Anti-Thrombin Antibodies in the Antiphospholipid Syndrome That Interfere with the Inactivation of Thrombin by Antithrombin. Journal of Immunology, 167(12), 7192–7198. https://doi.org/10.4049/jimmunol.167.12.7192

Galli, M., & Barbui, T. (1999). Antiprothrombin Antibodies: Detection and Clinical Significance in the Antiphospholipid Syndrome. Blood, 93(7), 2149–2157. https://doi.org/10.1182/blood.v93.7.2149

Justiz Vaillant AA, Goyal A, Varacallo MA. Systemic Lupus Erythematosus. [Updated 2023 Aug 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535405/

Yang R, Zubair M, Moosavi L. Prothrombin Time. [Updated 2024 Jan 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544269/

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