APS is a risk factor for arterial and/or venous thromboembolic disease and pregnancy morbidity (recurrent fetal loss, severe preeclampsia, and eclampsia).  APS may be present in 12-30% of cases of systemic lupus erythematosus. The diagnostic criteria for APS were defined an international consensus conference (Sapporo, 1998). The laboratory criteria for APS are repeatable positive tests at moderate to high levels at least six weeks apart for either:

Cardiolipin Antibody, IgG and IgM,Serum

Cardiolipin Antibody, IgG,Serum

Cardiolipin Antibody, IgM, Serum

Lupus Anticoagulant, Citrated Whole Blood

Although there is often concordance between ACL and LA, this is not always present. The rationale for requiring repeatable positive tests is to avoid potential false positives secondary to infectious disease since ACL may be induced by a variety of infectious agents, most notably syphilis. Infection-induced ACL are not associated with APS. They are directed at phospholipids alone while APS-associated ACL are also directed at the phospholipid binding protein called Beta-2-Glycoprotein I (B-2-GPI).  For this reason, reagents for ACL testing include a source of B-2-GPI.

Beta-2 Glycoprotein I Antibodies, IgG and IgM, Serum

Beta-2 Glycoprotein I IgG, Serum

Beta-2 Glycoprotein I IgM, Serum

Enzyme immunoassays (EIAs) for B-2-GPI itself have been reported by a number of investigators to be even more specific for APS; however they have not yet been included among the laboratory criteria pending further validation and standardization. Nevertheless, support for adding anti-Beta-2-GPI testing to ACL and lupus anticoagulant testing in the work-up of APS comes from studies reporting anti-Beta-2-GPI to be the only positive test in up to 10% of patients with evidence of APS. In addition, two studies report that the rate of thrombosis increases significantly from patient populations with a single positive anti-phospholipid screening test (27.6%), to those with two positive tests (38.8%) to those with three positive tests (66.7%).

Lupus anticoagulant tests are functional, clot-based tests that are performed in the Hemostasis Laboratory. An algorithm is used and the results are interpreted by a Pathologist. The algorithm is based on the recommendations for laboratory testing for lupus anticoagulants proposed by the Sapporo conference.

According to the Sapporo criteria, there should be:

  • Evidence of prolongation of at least one phospholipid dependent clotting test.

  • Evidence of continued prolongation after mixing with normal pooled plasma.

  • Evidence that this prolongation is dependent on phospholipids, therefore adding
     excess phospholipids results in shortening of the clotting time.

  • Exclusion of other coagulopathies.

Selected References:

Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthritis Rheum 1999; 42:1309-1311.

Viard JP, Amoura Z, Bach JF. Association of anti-beta-2-glycoprotein I antibodies with lupus-type circulating anticoagulants and thrombosis in SLE. Am J Med 1992; 93: 181-186.