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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3421-3431
Lupus Anticoagulants Form Immune Complexes With Prothrombin and
Phospholipid That Can Augment Thrombin Production in Flow
Susan L. Field,
Philip J. Hogg,
Elise B. Daly,
Yan-Ping Dai,
Barbara Murray,
Daniel Owens, and
Colin N. Chesterman
From 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; and the
Division of Immunology and Cell Biology, John Curtin School of Medical
Research, Australian National University, Canberra, Australia.
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.
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