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A functional coagulation test to identify anti-beta2-glycoprotein I dependent lupus anticoagulants
1Coagulation Laboratory, Laboratory for Clinical Biology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan, 185 (2P8), B-9000 Ghent, Belgium. katrien.devreese@uzgent.be
Introduction:
Lupus Anticoagulants (LAC) activity due to beta(2)-glycoprotein I (beta(2)GPI) antibodies shows a high correlation with thrombotic events. Since the binding of beta(2)GPI antibodies to phospholipids may be influenced by the final calcium chloride (CaCl(2)) concentration a discrimination between beta(2)GPI dependent LAC and beta(2)GPI independent LAC could be possible using clotting tests with various CaCl(2) concentrations and making them this way more sensitive to the presence of beta(2)GPI antibodies.
Materials And Methods:
I evaluated the effect of 5 mM, 8.3 mM, 10.3 mM and 17.9 mM final CaCl(2) concentration in a commonly used screening test for LAC, the PTT-LA, on LAC positive patients with and without beta(2)GPI antibodies.
Results:
Mean coagulation times of LAC patients negative for beta(2)GPI antibodies were significant shorter with 5 mM CaCl(2) in comparison with 8.3 mM and 10 mM (P<0.05 and P<0.01, respectively). In the LAC patients with positive beta(2)GPI antibodies no significant difference at 5 mM CaCl(2), 8.3 mM or 10 mM was observed. Mean coagulation times at 5 mM CaCl(2) were significant higher (P=0.003) in patients positive for beta(2)GPI antibodies than in patients negative for beta(2)GPI antibodies.
Conclusion:
The most remarkable observation was that the coagulation time, measured by PTT-LA at low final CaCl(2) concentration, is much more prolonged in the LAC positive beta(2)GPI antibody positive patients than in the LAC positive beta(2)GPI antibody negative patients. Thus, the competition with clotting factors for binding on phospholipids is stronger for beta(2)GPI antibodies than for other antibodies and explains the longer coagulation times in the presence of beta(2)GPI antibodies.
