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Anticardiolipin Antibodies

The first anticardiolipin antibody (ACA) tests were developed in the early 1900s as a screening test for syphilis.1 The Venereal Disease Research Laboratory (VDRL) test is a manual agglutination assay that detects antibodies to cardiolipin extracted from bovine heart tissue. Mass screening studies with the VDRL revealed that this test was not specific for syphilis. False-positive VDRL screening results were found to be significantly associated with lupus anticoagulants and risk of thrombosis. The first solid-phase immunoassays for antibodies to cardiolipin were developed in the early 1980s. These assays, designed to detect anticardiolipin IgA, IgG, and IgM isotypes, are approximately 100-fold more sensitive than the classical VDRL assay.1 The presence of anticardiolipin antibodies (especially those of moderate to high titer for IgG) is strongly associated with both arterial and venous thrombosis and recurrent pregnancy loss.2-4 The IgM and IgA isotypes of anticardiolipin antibody have also been shown to be associated with venous thrombosis.2,3,5 The distribution of isotypes of anticardiolipin antibody-positive patients with thrombosis has been found to be as follows:2

 

IgG

36%

IgM

17%

IgA

14%

Multiple

33%

In general, anticardiolipin antibodies are considered to be more sensitive than lupus anticoagulants for APS and are implicated in approximately five times more cases.2,3

  • At least one anticardiolipin antibody isotype can be detected in 80% to 90% of patients with APS.6
  • Approximately 90% of individuals with lupus anticoagulants will also be positive for at least one isotype of anticardiolipin antibody.5

Lupus anticoagulants are more specific for APS than anticardiolipin antibodies.2,6

  • The specificity of anticardiolipin antibodies for APS is increased with higher titer, especially for the IgG isotype.1,3

While there is frequent concordance between lupus anticoagulant and anticardiolipin antibody results, clinical situations occur in which one is present in the absence of the other.1,6

References

1. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med.2002 Mar 7; 346(10):752-763. PubMed 11882732

2. Bick RL. Antiphospholipid thrombosis syndromes. Clin Appl Thromb Hemost. 2001 Oct; 7(4):241-258. PubMed 11697705

3. Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome? J Autoimmun. 2000; 15(2):163-172. PubMed 10968904

4. Reddel SW, Krilis SA. Testing for and clinical significance of anticardiolipin antibodies. Clin Diagn Lab Immunol. 1999; 6(6):775-782. PubMed 10548562

5. Alving BM. The antiphospholipid syndrome: Clinical presentation, diagnosis, and patient management. In Kitchens CS, Alving BM, Kessler CM, eds. Consultative Hemostasis and Thrombosis. Philadelphia, Pa: WB Saunders; 2002:181-196.

6. Harris EN, Pierangeli SS, Gharavi AE. Diagnosis of the antiphospholipid syndrome: A proposal for use of laboratory tests. Lupus. 1998; 7(Suppl 2):S144-S148. PubMed 9814693

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