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Anticardiolipin Antibody 

  • Author: Yoon Chul Shin; Chief Editor: Eric B Staros, MD  more...
 
Updated: Apr 29, 2013
 

Reference Range

The quantitative measurement of anticardiolipin (aCL) antibody is important in diagnosing antiphospholipid syndrome (APS).

According to the Second International Anti-cardiolipin Standardization Workshop, the reference ranges of serum aCL are as follow:[1]

  • Low positive: Fewer than 20 G phospholipids (GPL), M phospholipids (MPL), A phospholipids (APL) units
  • Medium positive: 20 or more but fewer than 80 GPL, MPL, APL units
  • High positive: 80 or more GPL, MPL, APL units
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Interpretation

The presence of serum anticardiolipin (aCL) antibody without clinical symptoms does not support a diagnosis of antiphospholipid syndrome (APS). A positive result supports the diagnosis only in the presence of thrombosis or fetal loss. In addition, the test results must be positive at least 2 occasions 12 or more weeks apart to validate the diagnosis.

A higher aCL titer indicates more frequent clinical manifestations among individuals with APS.[2]

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Collection and Panels

Specifics for collection of anticardiolipin (aCL) antibody are as follows:

  • Container: Red-top tube (serum)
  • Specimen preparation: Transport minimum of 0.4 mL of serum to transport tube
  • Storage/transport temperature: Refrigerated at 2-8°C
  • Unacceptable conditions: Plasma, grossly visible hemolysis and lipemia
  • Stability (collection to initiation of testing [after separation from cells]): Refrigerated or frozen for 2-3 days
  • Method: Enzyme-linked immunoassay (ELISA) [3]
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Background

Description

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (APLA). APS is diagnosed when at least one requirement from both clinical and laboratory criteria are met.

Clinical criteria include the following:

  • Vascular thrombotic episodes in any tissue or organ
  • Pregnancy loss (≥1 unexplained loss of a normal fetus beyond the 10th gestational week, ≥1 premature birth before the 34th gestational week due to eclampsia or placental insufficiency, or ≥3 spontaneous abortions before the 10th gestational week)

Laboratory criteria include the following:

  • Lupus anticoagulant (LA) present in serum
  • Anticardiolipin (aCL) antibody of immunoglobulin G (IgG) and/or immunoglobulin M (IgM) isotype present in serum (>40 GPL or MPL units, or above the 99th percentile)
  • Anti–beta2 glycoprotein-I (b2-GPI) antibody of IgG and/or IgM isotype (in titer above the 99th percentile) in serum [4]

Although not included in the diagnostic criteria, other clinical symptoms, such as livedo reticularis, nephropathy, thrombocytopenia, cardiac valvular disease, and neurological symptoms are commonly associated comorbidities.[5]

An anionic side of the phospholipids that constitutes the cell membrane normally faces the cytoplasm. In the setting of initial injury, the anionic surface is exposed to the exterior. aCL binds to the anionic phospholipid on the platelet membrane and to the b2-GPI free flowing in the serum. Deposition of this aCL immune complex causes additional exposure of anionic phospholipids and platelet activation by unidentified signal transducing mechanisms. This cascade eventually leads to the formation of thrombosis. APLA refers to other prothrombotic antibodies that behave similarly to aCL. LA and anti–b2-GPI are among the APLAs.[6]

Indications/Applications

aCL testing is performed as part of the workup of excessive clotting episodes, along with LA and anti–b2-GPI antibody tests.

In addition, aCL testing is indicated in certain clinical settings.

aCL testing is warranted in young patients with unexplained arterial or venous thrombosis who lack evidence of atherosclerosis or emboli or develop thrombosis at unusual sites.[6] History of pregnancy loss also justifies aCL testing.

Specific criteria that link pregnancy complications to APS include one or more unexplained death of a morphologically normal fetus beyond the 10th week of gestation, one or more premature births before the 34th gestational week due to eclampsia or placental insufficiency, and three or more consecutive spontaneous abortions before the 10th gestational week.[7]

aCL assay is also indicated in cutaneous circulation disturbances without clear explanations, such as blue toe syndrome, ulcers resembling pyoderma gangrenosum, and livedo reticularis.

In addition, patients with systemic lupus erythematosus, autoimmune thrombocytopenia, or autoimmune hemolytic anemia should undergo aCL testing since APS can result from these disorders.[8]

Nonbacterial thrombotic endocarditis without malignancy should also prompt aCL testing for possible APS.[9]

Considerations

Although the IgA isotype of aCL is tested together with IgG and IgM isotype, it is not included in the diagnostic criteria of APS since the prevalence of IgA among patients with APS patients is significantly lower than that of IgG/IgM.[10] However, one study found that the IgA aCL was the only isotype present in 82% of aCL-positive Afro-Caribbean patients.[11] The level of IgG aCL demonstrates stronger association with the clinical symptoms of APS. Thrombosis, recurrent fetal loss, and thrombocytopenia were found to occur more frequently at higher titer of IgG (>35 GPL units) than the others.[12]

Although aCL testing has high sensitivity for APS, it has relatively lower specificity, especially when the measured value is low positive (< 20 GPL, MPL, or APL units). Various conditions are associated with low positive results in aCL ELISA, including syphilis, Q fever, hepatitis C, AIDS, tuberculosis, connective-tissue diseases, and drug-induced disorders. In fact, LA reaction is regarded as a more specific test for APS since it is found much less commonly in other disorders.[13] Additionally, the presence of IgM rheumatoid factor can produce false positive IgM aCL.[14]

Despite attempts to standardize the testing and reporting practices, multi-laboratory comparative studies and quality assurance programs indicate that different laboratories may report substantially variable aCL values even from the same sample.[15]

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Contributor Information and Disclosures
Author

Yoon Chul Shin St Louis University School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

References
  1. Harris EN. Special report. The Second International Anti-cardiolipin Standardization Workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group. Am J Clin Pathol. 1990 Oct. 94(4):476-84. [Medline].

  2. Wong RC, Gillis D, Adelstein S, et al. Consensus guidelines on anti-cardiolipin antibody testing and reporting. Pathology. 2004 Feb. 36(1):63-8. [Medline].

  3. Lakos G, Favaloro EJ, Harris EN, et al. International consensus guidelines on anticardiolipin and anti-ß2-glycoprotein I testing: report from the 13th International Congress on Antiphospholipid Antibodies. Arthritis Rheum. 2012 Jan. 64(1):1-10. [Medline].

  4. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb. 4(2):295-306. [Medline].

  5. Kumar, Vinay, Abul K. Abbas, Nelson Fausto, Stanley L. Cotran. Robbins, Ramzi S. Robbins and Cotran Pathologic Basis of Disease. Philadelphia: Elsevier Saunders; 2005.

  6. Arnout J, Vermylen J. Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotic disease. J Thromb Haemost. 2003 May. 1(5):931-42. [Medline].

  7. Lockshin MD. Pregnancy loss and antiphospholipid antibodies. Lupus. 1998. 7 Suppl 2:S86-9. [Medline].

  8. Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002 Apr. 46(4):1019-27. [Medline].

  9. Reisner SA, Brenner B, Haim N, Edoute Y, Markiewicz W. Echocardiography in nonbacterial thrombotic endocarditis: from autopsy to clinical entity. J Am Soc Echocardiogr. 2000 Sep. 13(9):876-81. [Medline].

  10. Gharavi AE, Harris EN, Asherson RA, Hughes GRV. Anticardiolipin antibody isotype distribution and phospholipid specificity. Ann Rheum Di. 1987. 46:1-6.

  11. Molina JF, Gutierrez-Urena S, Molina J, et al. Variability of anticardiolipin antibody isotype distribution in 3 geographic populations of patients with systemic lupus erythematosus. J Rheumatol. 1997 Feb. 24(2):291-6. [Medline].

  12. Harris EN, Chan JK, Asherson RA, Aber VR, Gharavi AE, Hughes GR. Thrombosis, recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin antibody test. Arch Intern Med. 1986 Nov. 146(11):2153-6. [Medline].

  13. Pierangeli SS, Harris EN. A quarter of a century in anticardiolipin antibody testing and attempted standardization has led us to here, which is?. Semin Thromb Hemost. 2008 Jun. 34(4):313-28. [Medline].

  14. Agopian MS, Boctor FN, Peter JB. False-positive test result for IgM anticardiolipin antibody due to IgM rheumatoid factor. Arthritis Rheum. 1988 Sep. 31(9):1212-3. [Medline].

  15. Favaloro EJ, Wong RC, Silvestrini R, et al. A multilaboratory peer assessment quality assurance program-based evaluation of anticardiolipin antibody, and beta2-glycoprotein I antibody testing. Semin Thromb Hemost. 2005 Feb. 31(1):73-84. [Medline].

 
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