print Print Back Back

Antiprothrombin Antibody

Policy Number: MP-096

Latest Review Date: May 2022

Category: Laboratory


Antiprothrombin antibody testing is considered investigational.


Anti-phospholipid syndrome (APS) is an autoimmune condition characterized by moderate-to-high levels of circulating anti-phospholipid antibodies and the presence of venous and arterial thromboses, autoimmune thrombocytopenia, fetal loss, and other clinical features, including transient ischemic attacks, amaurosis fugax, Coombs-positive hemolytic anemia, and livedo reticularis.

Detection of antiprothrombin antibodies is used to aid in the diagnosis of antiphospholipid syndrome (APS) and to confirm antiprothrombin antibody presence in patients with lupus anticoagulants and hypoprothrombinemia using the Enzyme-linked immunosorbent assay (ELISA) method.


This policy was updated with literature review performed most recently through May 10, 2022.

Summary of Evidence

At this time, antiprothrombin antibody patient stratification provides additional information that may be useful for research and for treatment, but does not alter the diagnosis. Research of the current literature suggests that there is a paucity of evidence to prove that antithrombin antibodies increase the risk of thromboembolic events. More prospective, longitudinal clinical studies are needed to clarify the clinical relevance of this information. The utility of this testing cannot be proven at this time and therefore is considered investigational.

Practice Guidelines and Position Statements

American College of Obstetricians and Gynecologists

Guidelines on Anti-phospholipid syndrome (APS) from the American College of Obstetricians and Gynecologists (ACOG, 2005) stated that testing for anti-prothrombin antibodies "cannot be recommended for clinical use at this time."

British Committee for Standards in Haematology

The most current guidelines state that the clinical significance of anti-prothrombin antibodies has not been defined (British Committee for Standards in Haematology, 2000).

The Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology

The Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology reached the following conclusion: "Antiprothrombin antibodies generally exhibit poor specificity for venous thrombosis and recurrent fetal loss and may be found in patients with infection.  Their precise clinical significance is not yet clear.  One report has claimed an association with myocardial infarction, but more work is required to clarify the clinical importance of this observation."

U.S. Preventative Services Task Force

Not applicable


Prothrombin, antiprothrombin antibody, antiphospholipid antibody, APL, antiphospholipid syndrome, APS, Hughes syndrome, beta-2 glycoprotein I, thrombosis, pregnancy loss, thrombocytopenia


Not applicable


Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity. Special benefit consideration may apply. Refer to member’s benefit plan.


CPT codes:


Unlisted Immunology procedure


  1. Amengual O, Forastiero R, Sugiura-Ogasawara M, et al. Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: Results of an international multicentre study. Lupus. 2017; 26(3):266-276.
  2. American College of Obstetricians and Gynecologists (ACOG). Clinical Management Guidelines for Obstetrician-Gynecologists. ACOG Practice Bulletin, November 2005, No. 68.
  3. Atsumi T and Koike T. Antiprothrombin antibody: why do we need more assays? Lupus, 2010 Apr; 19(4):436-9
  4. Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R, de Groot P, Lakos G, Lambert M, Meroni P, Ortel TL, Petri M, Rahman A, Roubey R, Sciascia S, Snyder M, Tebo AE, Tincani A, Willis R. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev. 2014 Sep; 13(9):917-30. Epub 2014 May 10.
  5. Bertolaccini ML, Gomez S, et al. Antiphospholipid antibody tests: Spreading the net. Annals of the Rheumatic Diseases 2005; 64: 1639-1643.
  6. Branch W; Obstetric Task Force. Report of the Obstetric APS Task Force: 13th International Congress on Antiphospholipid Antibodies, 13th April 2010. Lupus. 2011; 20(2):158-164.
  7. British Committee for Standards in Haematology, Haemostasis and Thrombosis Task Force.  Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol. 2000; 109:704-715.
  8. Donohoe, Siobhan. Detection and clinical associations of antiprothrombin antibodies. American Journal of Medicine, February 2001, Vol. 110, No. 3.
  9. Giannakopoulos B, Passam F, Ioannou Y, Krilis SA. How we diagnose the antiphospholipid syndrome. Blood. 2009;113(5):985
  10. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  11. Kalashnikova, L.A., Korczyn, A.D., et al. Antibodies to prothrombin in patients with Sneddon’s syndrome. Neurology, July 1999, Vol. 53, No. 1.
  12. Lim W. Antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2013; 2013:675-80.
  13. Lopez Luis R, Dier Ken J, et al. The prevalence and clinical significance of antiprothrombin antibodies in patients with antiphospholipid syndrome. American Biotechnology Laboratory, April 2003.
  14. Merrill, Joan T. Which antiphospholipid antibody tests are most useful?, Rheumatic Diseases Clinics of North America, August 2001, Vol. 27, No. 3.
  15. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4(2):295.
  16. Oku K, Atsumi T, Amengual O, Koike T. Antiprothrombin antibody testing: Detection and clinical utility. Semin Thromb Hemost. 2008; 34(4):335-339.
  17. Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, De Groot PG, Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009; 7(10):1737.
  18. Reber G, Tincani A, Sanmarco M, de Moerloose P, Boffa MC, Standardization group of the European Forum on Antiphospholipid Antibodies. Proposals for the measurement of anti-beta2-glycoprotein I antibodies. Standardization group of the European Forum on Antiphospholipid Antibodies. J Thromb Haemost. 2004; 2(10):1860.
  19. Tsutsumi A, et al. Significance of antiprothrombin antibodies in patients with systemic lupus erythematosus: clinical evaluation of the antiprothrombin assay and the antiphosphatidylserine/prothrombin assay, and comparison with other antiphospholipid antibody assays. Mod Rheumatol. 2006 Jun; 16(3): 158–164.


Medical Policy Group, February 2003, (1)

Medical Policy Administration Committee, February 2003

Available for comment February 19-April 7, 2003

Medical Policy Group, February 2005 (1)

Medical Policy Group, February 2007 (1)

Medical Policy Group, February 2009 (1)

Medical Policy Group, June 2011 (1) Update to Key Points and References

Medical Policy Group, September 2012 (3): Active Policy but no longer scheduled for regular literature reviews and updates.

Medical Policy Group, November 2012: 2013 Coding Update – added Code 86849

Medical Policy Group, June 2019 (9): Update to Description, Key Points and References. No change to policy statement.

Medical Policy Group, May 2021 (9): Updates to Description, Key Points, References. Policy statement updated to remove “not medically necessary,” the word “testing” added, no change to policy intent.

Medical Policy Group, October 2021 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, May 2022 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.