Lupus anticoagulants form immune complexes with prothrombin and phospholipid that can augment thrombin production in flow.
Lupus anticoagulants (LA) are a family of autoantibodies that are associated with in vitro anticoagulant activity but a strong predisposition to in vivo thrombosis. They are directed against plasma phospholipid binding proteins, including prothrombin. We found that a murine monoclonal antiprothrombin antibody and 7 of 7 LA IgGs tested enhanced binding of prothrombin to 25:75 phosphatidyl serine:phosphatidyl choline vesicles in a concentration-dependent manner. We hypothesized that enhanced binding of prothrombin to phospholipid in the presence of LA IgG might result in increased thrombin production when reactions are performed in flow. Thrombin production by purified prothrombinase components was measured in a phospholipid-coated flow reactor. The flow reactor was incubated with prothrombin, calcium ions, and the IgGs and then perfused with prothrombin, calcium ions, the IgGs, factor Va, and factor Xa. A murine monoclonal antiprothrombin antibody and 4 of 6 LA IgGs from patients with a history of thrombosis increased thrombin production up to 100% over control in the first 15 minutes. In summary, LA IgGs concentrate prothrombin on a phospholipid surface that can augment thrombin production by prothrombinase in flow. These observations suggest that LA might propagate coagulation in flowing blood by facilitating prothrombin interaction with the damaged blood vessel wall.
Field
S L
SL
The Centre for Thrombosis and Vascular Research, School of Pathology, University of New South Wales, and the Department of Haematology, Prince of Wales Hospital, Sydney, Australia.
Hogg
P J
PJ
Daly
E B
EB
Dai
Y P
YP
Murray
B
B
Owens
D
D
Chesterman
C N
CN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016682:Lupus Coagulation Inhibitor / Q000276:immunology*; D008177:Lupus Vulgaris / Q000276:immunology*; D051379:Mice; D010743:Phospholipids / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D011516:Prothrombin; D013917:Thrombin