Lupus Anticoagulants:First French Interlaboratory Etalonorme Survey

Abstract

In 1994, the French National Quality Control Group for Hematology, Etalonorme, conducted a large-scale interlaboratory survey concerning the detection of lupus anticoagulants (LA) involving all the 4,500 French laboratories. Each laboratory received the same batch of a lyophilized citrated plasma (94B3) prepared from a patient with LA that had been confirmed by all the techniques used in the intralaboratory study. In the interlaboratory survey, the screening test was activated partial thromboplastin time (A FIT); mean A KIT calculated from the results reported by 4,029 labs was prolonged (clotting ratio = 1.44) with a large dispersion (coefficients of variation = 18.8%). APTT of the mixture 94B3 + Normal plasma were performed by 2,698 laboratories. No correction of APTT was obtained (R = 1.36, Rosner index = 24) with a wide variation between reagents (17 < Rosner index < 39). OnlyThis report originated from the first French national survey on lupus anticoagulants (LA). Lupus anticoagulants are heterogeneous autoantibodies directed against anionic phospholipids or against a protein-phospholipid complex 1 " 3 and constitute one member of the family of antiphospholipid antibodies. These acquired inhibitors of coagulation are described in patients with systemic lupus erythematosus or related autoimmune diseases and in otherwise healthy persons. 4,5 Their presence is closely associated with the occurrence of arterial and venous thromboembolism, thrombocytopenia, fetal loss, valvular heart disease, and dermatologic manifestations.6 7 The thrombotic predisposition is sustained by numerous relevant pathogenetic mechanisms, including interference with numerous compounds of the hemostasis pathways. 8 The Lupus Anticoagulant/Antiphospholipid Antibody Subcommittee published recommendations for testing and identification of LA in 1991 9 and a revision in 1995. In France, the national quality control group, Etalonorme," conducted an interlaboratory survey concerning LA detection involving all 4,500 French laboratories. The aim of the survey was to evaluate, on a large scale, the level of French laboratory performances and to check the sensitivity and specificity of the different tests and reagents used. The final goal was to draw up an educational program concerning LA for French biologists, and to make recommendations for testing.All the laboratories received the same batch of commercial lyophilized human plasma containing an LA. Biologists had to perform the tests with their own reagents and to follow the recommended procedure for testing and detection of LA (Appendix). The screening test was activated partial thromboplastin time (APTT), the inhibitor was identified by mixing studies, and a confirmatory test had to be chosen from a proposed list including tests performed with a reduced or an augmented amount of phospholipids. The results indicate that the reagents have different sensitivities. Seventy percent of the laboratories suspected the presence of LA, but only 15% performed the confirmatory test. MATERIALS AND METHOD...

Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature

“…These are important issues, because the lack of internationally accepted reference and control materials, the variability of the reagents, instruments, and combinations of tests may greatly affect lupus anticoagulant measurement. [49][50][51][52] Lupus anticoagulants have an odds ratio for thrombosis 5 to 16 times higher than controls. These figures are very close to those reported by Wahl and coworkers for deep vein thrombosis in patients with 53 and without 54 systemic lupus erythematosus.…”

Antiphospholipid Antibodies: Laboratory and Pathogenetic Aspects

“…140−145 Numerous studies have documented the suboptimal performance of LA determination; most were conducted by societies, such as the British Society for Haematology, 140 the ISTH, 117 the College of American Pathologists, 146 the Société Française de Biologie Clinique, 147 the European Concerted Action on Thrombophilia (ECAT), 144 and the Italian Federation of Anticoagulation Clinics 148 or by quality control organizations, such as the United Kingdom National External Quality Assessment Scheme (NEQAS) 143,145 and the Etalonorme, a French National Quality Control Group for Hematology. 149 The percentage of correct detection of standard samples with high LA activity ranged from 82% to 99% in different studies. 140,[143][144][145]148 The highest percentage was achieved in a study in which the standard sample was normal plasma to which monoclonal anti-β2GPI with LA activity was added.…”

“…148 A study involving approximately 4,500 laboratories in France showed that only 41% of laboratories detected LA in a standard LApositive plasma sample. 149 Another study, with a different design, in which no standard samples were distributed but each laboratory tested their routine samples either using their routine practice or using a standardized procedure with mutually agreed cut-off levels, showed significant variation in levels of agreement between the two procedures, as assessed by the kappa index; absolute concordance occurred in 81% of the specimen population and absolute discordance in 7% of samples. 142 Sources of variation in the detection of LA are multiple and can be due to pre-analytical, analytical, and post-analytical factors.…”

Antiphospholipid Syndrome: Association Between Laboratory Tests and Clinical Practice

“…Nevertheless, the diagnosis of lupus anticoagulants may remain cumbersome and difficult. This is partly due to the high degree of heterogeneity in reagents, methods, instrumentations, and the methods used to express the results, as pointed out by national and international surveys [22][23][24]. The first French interlaboratory survey on lupus anticoagulants reported a correct diagnosis by only 41% of more than 4,000 laboratories [22].…”

“…This is partly due to the high degree of heterogeneity in reagents, methods, instrumentations, and the methods used to express the results, as pointed out by national and international surveys [22][23][24]. The first French interlaboratory survey on lupus anticoagulants reported a correct diagnosis by only 41% of more than 4,000 laboratories [22]. A plasma containing anti-factor VIII antibodies was misdiagnosed as lupus anticoagulant-positive by 20% of the laboratories participating to a survey of the European Concerted Action on Thrombophilia (ECAT) [23] .…”