Antiphospholipid antibodies (aPL), notably the lupus anticoagulant and anticardiolipin antibodies, are the serological hallmarks of the antiphospholipid syndrome. Thrombosis and pregnancy complications

Antiphospholipid antibodies (aPL), notably the lupus anticoagulant and anticardiolipin antibodies, are the serological hallmarks of the antiphospholipid syndrome. Thrombosis and pregnancy complications are the most prominent clinical manifestations of this syndrome. This paper provides the clinician with guidelines for ordering and interpreting tests for aPL and discusses consequences for treatment if persistently positive tests are found. I N T R O D U C T I O N Twenty years ago it was recognised that in patients with systemic lupus erythematosus (SLE) the presence of circulating antiphospholipid antibodies (aPL), notably lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL), was associated with thrombosis, pregnancy complications and thrombocytopenia. This association was termed antiphospholipid syndrome (APS). It was soon recognised that APS can also occur in patients without an underlying systemic autoimmune disease (primary APS, PAPS). With the current wide availability of aPL tests, clinicians need to know when such tests should be ordered, how results should be interpreted and what the consequences are of a positive test. H I S T O R Y O F A P L It was in 1906 that aPL were described for the first time as complement-fixing antibodies that react with alcoholic extracts of beef heart in patients with syphilis. Later on, the essential component within the complex antigen was identified as cardiolipin, a negatively charged mitochondrial phospholipid. This observation led to the development of an agglutination test known as the Venereal Disease Research Laboratory (VDRL) test, which is currently still used as a screening test for syphilis. Mass screening of blood during and after the second world war led to the recognition that the VDRL test can be transient or persistently positive without clinical or serological evidence of syphilis. Transient biological false-positive reactions mainly occurred with (nonsyphilitic) infections and persistent positive reactions were found in patients with systemic autoimmune disorders, mainly systemic lupus erythematosus (SLE). Associations between a positive VDRL test and clinical manifestations in SLE patients were never reported. In 1952, Conley and Hartman described in patients with SLE a peculiar inhibitor of in vitro coagulation, which has been known as lupus anticoagulant (LAC) since 1972. The phenomenon refers to antibodies that interfere with the assemblage of proteins of the coagulation cascade on a phospholipid template. In vitro plasma clotting times normalise when extra phospholipids are added to the test system. For many years the only importance of identification of LAC was that, in contrast to most other inhibitors of coagulation, it was not associated with bleeding. As many patients with LAC had a biologically false-positive VDRL test and coagulation tests are relatively complicated, requiring among other things adequately processed plasma samples and a relatively long hand-on time, sensitive solid phase immunoassays for the detection of antibodies to cardiolipin were developed in the 1980s. In contrast to © 2004 Van Zuiden Communications B.V. All rights reserved. Clinical consequences of antiphospholipid antibodies R.H.W.M. Derksen, P.G. de Groot Department of Rheumatology and Clinical Immunology, Room F02.127, Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre, Heidelberglaan 100, 3584 GA Utrecht, the Netherlands, tel: +31 (0)30-2507357, fax: +31 (0)30-2523741, e-mail: [email protected], corresponding author