Laboratory Testing for Antibodies Associated with Antiphospholipid Antibody Syndrome

Abstract

Of the several types of antiphospholipid antibodies (aPL) described, lupus anticoagulant (LA) antibodies and anticardiolipin antibodies (aCL) are the types most clearly associated with antiphospholipid antibody syndrome (APS), the latter being the focus of this chapter. The Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin tests were then developed, both employing purified cardiolipin combined with cholesterol and lecithin as the antigen. Classification of patients with APS considers both clinical and laboratory criteria. The syndrome is classified as primary APS when not associated with another disease and accounts for over 50% of cases. The first category of aPL, LA antibodies, are detected with certain phospholipid-dependent coagulation assays. Definite APS is present when at least one clinical criterion and one laboratory criterion are present. LAs are antibodies that are prothrombotic in vivo but display anticoagulant properties in vitro (i.e., they prolong certain coagulation tests). Antibodies associated with APS that are detected in aCL ELISAs were originally thought to bind to the phospholipid molecule. An appreciation of the presence of aPL in systemic lupus erythematosus (SLE) patients, and their association with thrombosis, led to the development of an RIA for detection of aCL antibodies and subsequently an ELISA-based format. As discussed in the chapter, cutoff levels should be validated in each laboratory performing aPL testing. Alternative phospholipids and/or cofactor antibodies may be detected in patients with APS. Occasional patients with APS do not have aCL, LA, or β2GPI antibodies.