Abstract Number: PB1919
Meeting: ISTH 2020 Congress
Theme: Thrombotic Microangiopathies » Antiphospholipid Syndrome
Background: The presence of lupus anticoagulant (LA) is strongly correlated with an increased risk of thrombosis. LA is a prolongation of the clotting time that can be attenuated by addition of an excess of phospholipids and is caused by autoantibodies against β2-glycoprotein I (β2GPI) or prothrombin. The mechanism behind the paradoxical association of thrombosis in vivo and prolonged clotting times in vitro remains unclear. In order to solve this paradox, we need to understand how these autoantibodies cause LA.
Aims: To elucidate the mechanism of action of LA caused by anti-β2GPI and anti-prothrombin antibodies.
Methods: The effects of a panel of monoclonal anti-β2GPI and anti-prothrombin antibodies on coagulation were analyzed in plasma and with purified coagulation factors. Results were confirmed in plasma from patients positive for LA.
Results: Addition of anti-β2GPI or anti-prothrombin antibodies to plasma caused a phospholipid-dependent increase in clotting time in FXa-initiated coagulation tests. In contrast, they did not prolong clotting times in plasma containing only active Factor V (FVa), or when coagulation was initiated with preformed prothrombinase complex. Next, clotting tests were performed in plasma from patients positive for LA, before and after treatment with the FV activating snake venom enzyme RVV-V. RVV-V-mediated FV activation strongly attenuated the LA phenomenon. Combined, these data support a role for FV activation in the mechanism of action of antiphospholipid antibodies. Analysis of FXa-mediated activation of FV with purified coagulation factors confirmed that both anti-β2GPI and anti-prothrombin antibodies attenuate FV activation at limiting phospholipid concentrations, but have no effect on FV activation at high phospholipid concentrations. Binding studies showed that β2GPI-antibody complexes directly interacted with FV, whereas prothrombin-antibody complexes did not.
Conclusions: Anti-β2GPI and anti-prothrombin antibodies cause LA through interference with the activation of FV by FXa through different mechanisms of action.
To cite this abstract in AMA style:
Noordermeer T, Molhoek JE, Sebastian SAE, Drost-Verhoef S, van Wesel ACW, de Groot PG, Meijers JCM, Urbanus RT. Anti-β2-Glycoprotein I and Anti-Prothrombin Antibodies Cause Lupus Anticoagulant by Interfering with Factor Xa-Mediated Factor V Activation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/anti-%ce%b22-glycoprotein-i-and-anti-prothrombin-antibodies-cause-lupus-anticoagulant-by-interfering-with-factor-xa-mediated-factor-v-activation/. Accessed September 24, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/anti-%ce%b22-glycoprotein-i-and-anti-prothrombin-antibodies-cause-lupus-anticoagulant-by-interfering-with-factor-xa-mediated-factor-v-activation/