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Anticardiolipin antibodies are often present in individuals with the antiphospholipid antibody syndrome.1,2
ACA can often be observed during the convalescent phase of acute bacterial and viral infections and in individuals with syphilis. These infection-induced antibodies are usually transient and are not associated with an increased risk of clinical complications. In general, all patients who test positive for ACA should be retested after six to eight weeks to rule out transient antibodies that are usually of no clinical significance.
Individuals with the antiphospholipid antibody syndrome (APS) have an increased risk for stroke, myocardial infarction, venous thrombosis, thromboembolism, thrombocytopenia, and/or recurrent miscarriages. In 1999, an international consensus conference found that one criterion for the serologic diagnosis of “definite antiphospholipid syndrome” is the presence of anticardiolipin antibody of IgG and/or IgM isotype, at medium or high titer, on two or more occasions, at least six weeks apart.3 The presence of ACA of moderate to high titer for IgG is strongly associated with both arterial and venous thrombosis and recurrent pregnancy loss.4-6 The IgM isotype of ACA has also been shown to be associated with venous thrombosis.4 Other studies found that ACA of the IgA isotype at moderate to high titer can also be associated with increased risk of APS.2,6
ACA antibodies are quite common in the general population and are not always associated with APS. Studies indicate that there is a higher prevalence of IgM positives than IgG in the general population with these isotypes occurring in 9.4% and 6.5% of the population, respectively.7 The incidence of these ACA is even higher in normal pregnancy with detection rates of 17% for IgM and 10.6% for IgG.8 Many of these antibodies are transient and not associated with APS. The diagnosis of APS should not be made on the basis of a single ACA result but rather on repeated positive results obtained at least six weeks apart.1
The Venereal Disease Research Laboratory (VDRL) agglutination test that has been used for decades in the diagnosis of syphilis is based on the detection of antibodies to cardiolipin.9 The first solid-phase immunoassays for ACA were developed in the early 1980s.9 These solid-phase assays are at least 100-fold more sensitive than the classical VDRL assay and produce many more positive results. In general, ACA are considered to be more sensitive than lupus anticoagulants (LA) for the detection of APS.4 The ACA test is positive in 80% to 90% of patients with APS,10 and ACA are implicated in approximately five times more cases of APS than are LA;2 however, LA are considered to be more specific for APS than ACA.2,10 Due to the heterogeneity of antibodies associated with APS, both LA and ACA testing is recommend when APS is suspected.4,11
ACA are frequently observed in patients with other autoimmune disorders and malignancies. Individuals with ACA secondary to these other conditions are at increased risk of developing APS. A variety of therapeutic drugs can induce the production of ACA. These drug-induced antibodies may be clinically significant if they persist.2,12
1. Adcock DM, Bethel MA, Macy PA. Coagulation Handbook . Aurora, Colo: Esoterix-Colorado Coagulation; 2006.
2. Bick RL. Antiphospholipid thrombosis syndromes. Clin Appl Thromb Hemost. 2001 Oct; 7(4):241-258. PubMed 11697705
3. Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: Report of an international workshop. Arthritis Rheum. 1999 Jul; 42(7):1309-1311. PubMed 10403256
4. Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome? J Autoimmun. 2000 Sep; 15(2):163-172. PubMed 10968904
5. Reddel SW, Krilis SA. Testing for and clinical significance of anticardiolipin antibodies. Clin Diagn Lab Immunol. 1999 Nov; 6(6):775-782. PubMed 10548562
6. López LR, Santos ME, Espinoza LR, et al. Clinical significance of immunoglobulin A versus immunoglobulins G and M anticardiolipin antibodies in patients with systemic lupus erythematosus. Correlation with thrombosis, thrombocytopenia, and recurrent abortion. Am J Clin Pathol. 1992 Oct; 98(4):449-454. PubMed 1415024
7. Vila P, Hernández MC, López-Fernández MF, et al. Prevalence, follow-up and clinical significance of the anticardiolipin antibodies in normal subjects. Thromb Haemost. 1994 Aug; 72(2):209-213. PubMed 7831653
8. Soloninka CA, Laskin CA, Wither J, Wong D, Bombardier C, Raboud J. Clinical utility and specificity of anticardiolipin antibodies. J Rheumatol. 1991 Dec; 18(12):1849-1855. PubMed 1795324
9. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. 2002 Mar 7; 346(10):752-763. PubMed 11882732
10. 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
11. Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: An update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost. 1995 Oct; 74(4):1185-1190. PubMed 8560433
12. Jenson R. The antiphospholipid antibody syndrome. Clin Hemost Rev. 2001 Nov; 15(11).
