Lupus Anticoagulant (LA) Testing: Performance of Clinical Laboratories Assessed by a National Survey Using Lyophilized Affinity-purified Immunoglobulin with LA Activity

Abstract

Abstract Background: Lupus anticoagulant (LA) screens are frequently ordered in the workup of thrombophilic patients or women with fetal loss. The sensitivity and specificity of LA detection vary depending on the choice of tests, cutoff values, and results interpretation. This variation is detrimental to patient management because persistent LA positivity in patients with a history of thrombosis is a requisite for long-term anticoagulation therapy. Numerous surveys have been performed to assess the state of the art for LA diagnosis. The control plasmas used in these surveys were from LA-positive or -negative patients or were normal plasmas with monoclonal antibodies against human β2-glycoprotein I (β2-GPI) added. Methods: A large number of laboratories were asked to test a common set of lyophilized plasmas for LA, including three normal plasmas, to which increasing amounts of affinity-purified IgG from a patient positive for anti-β2-GPI had been added, and three LA-negative plasmas: one normal, one with a coagulation deficiency, and one with heparin. Results: Overall, 69, 68, and 59 of 70 participants were able to detect LA in plasmas with high, intermediate, and low potency (sensitivity, 99%, 97%, and 84%). Conversely, 69, 50, and 53 of 70 were able to rule out LA in the normal, heparinized, and deficient plasma (specificity, 99%, 71%, and 76%). Conclusions: Sensitivity for LA detection is satisfactory, whereas specificity could be improved. Surveys for LA detection should be carried out on a regular basis because they may help improve performance. Plasmas containing graded amounts of affinity-purified human anti-β2-GPI may be used as a convenient source of well-characterized naturally occurring LA material.