A functional coagulation test to identify anti-β2-glycoprotein I dependent lupus anticoagulants

IntroductionLupus Anticoagulants (LAC) activity due to β2-glycoprotein I (β2GPI) antibodies shows a high correlation with thrombotic events. Since the binding of β2GPI antibodies to phospholipids may be influenced by the final calcium chloride (CaCl2) concentration a discrimination between β2GPI dependent LAC and β2GPI independent LAC could be possible using clotting tests with various CaCl2 concentrations and making them this way more sensitive to the presence of β2GPI antibodies.Materials and methodsI evaluated the effect of 5 mM, 8.3 mM, 10.3 mM and 17.9 mM final CaCl2 concentration in a commonly used screening test for LAC, the PTT-LA, on LAC positive patients with and without β2GPI antibodies.ResultsMean coagulation times of LAC patients negative for β2GPI antibodies were significant shorter with 5 mM CaCl2 in comparison with 8.3 mM and 10 mM (P < 0.05 and P < 0.01, respectively). In the LAC patients with positive β2GPI antibodies no significant difference at 5 mM CaCl2, 8.3 mM or 10 mM was observed.Mean coagulation times at 5 mM CaCl2 were significant higher (P = 0.003) in patients positive for β2GPI antibodies than in patients negative for β2GPI antibodies.ConclusionThe most remarkable observation was that the coagulation time, measured by PTT-LA at low final CaCl2 concentration, is much more prolonged in the LAC positive β2GPI antibody positive patients than in the LAC positive β2GPI antibody negative patients. Thus, the competition with clotting factors for binding on phospholipids is stronger for β2GPI antibodies than for other antibodies and explains the longer coagulation times in the presence of β2GPI antibodies.