The Detection of Lupus Anticoagulants in Hemophiliacs: The Need for Different Assay Systems

Abstract number: P0215

ME¹ Mancuso, E¹ Santagostino, PL² Meroni, M¹ Clerici, V¹ Chantarangkul, R¹ Bader, A¹ Tripodi, PM¹ Mannucci

¹¹Angelo Bianchi Bonomi Hemophilia & Thrombosis Center, IRCCS Maggiore Hospital, Milan, Italy ¹¹Angelo Bianchi Bonomi Hemophilia & Thrombosis Center, IRCCS Maggiore Hospital, Milan, Italy ²²Department of Internal Medicine and University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy

Inhibitors against FVIII prolong phospholipids-dependent tests and are associated with an increased risk of bleeding. Lupus anticoagulants (LAs) also prolong phospholipids-dependent tests associated with an increased risk of thrombosis. Other antiphospholipid antibodies (APA) can be detected in a solid-phase enzyme-linked immunosorbent assay and may coexist with LAs in a large number of patients. Some hemophiliacs may bear both, LA/APA and FVIII inhibitors, and the clinical laboratory should be able to distinguish these different types of anticoagulants. With this goal the LA/APA pattern was investigated in 50 patients with hemophilia A, 27 with inhibitors. Anti-FVIII inhibitor was measured according to the Bethesda method. LA detection was performed with silica clotting time (SCT), dilute Russell viper venom tests (dRVVT), and an APTT with hexagonal phospholipids (StaClot LA). The 3 main types of solid-phase APA, anti-cardiolipin, anti-prothrombin and anti-b₂ glycoprotein I (b₂GPI), were also searched. The prevalence of LA positivity according to SCT, commercial dRVVT and StaClot LA was higher in inhibitor patients than in the other hemophiliacs (4% vs 0, 22% vs 9%, 31% vs 5%, respectively). Thirteen hemophiliacs (26%), 11 with inhibitors, had at least one positive LA test; 3/13 (2 with inhibitors) tested positive with two tests and one inhibitor patient with three tests. Solid-phase APA antibodies were negative in all hemophiliacs, but one non-inhibitor patient who tested slightly positive for anti-prothrombin IgM antibodies. Our results with different assay systems to detect LA and APA showed that the majority of hemophiliacs who tested positive had inhibitors suggesting an influence of anti-FVIII inhibitors on the LA assays. True LA/APA positive hemophiliacs with two and three positive tests were very few, 6% and 2%, respectively. In conclusion, 2 or more tests, possibly with different assay designs, should be used to rule in or out LA in patients with hemophilia.