Anti-Prothrombin Antibodies Cause Thrombosis In A Novel Qualitative Ex-Vivo Animal Model
Publication Type
Original research
Authors
Haj-Yahia S
Sherer Y
Blank M
Kaetsu H
Smolinsky A
Anti-prothrombin antibodies (aPT) are associated with thrombotic
manifestations, and their association with reproductive failure is
debatable. The aim of this study was to examine whether aPT could induce
thrombosis and other clinical manifestations of the anti-phospholipid
syndrome (APS). Mice were immunized with either prothrombin,
beta2-glycoprotein-I (beta2GPI), or beta2GPI followed by prothrombin.
The presence of clinical manifestation of APS, including
thrombocytopenia, lupus anticoagulant and fetal resorption rates, was
evaluated in all mice groups compared with nonimmunized mice. Thrombosis
was studied in a novel ex-vivo model in which the aorta was sutured for
1 min and the presence or absence of visible thrombus was qualitatively
evaluated. Immunized mice developed high autoantibody levels directed
towards their immunizing autoantigens. The groups immunized with
beta2GPI or beta2GPI/prothrombin, but not with prothrombin alone,
developed prolonged aPTT, thrombocytopenia and increased fetal
resorption rate. All prothrombin-immunized mice as well as most
beta2GPI/prothrombin-immunized mice developed visible thrombus within
the aorta. Some beta2GPI immunized mice developed very mild thrombus.
None of the CFA/PBS-injected or the nonimmunized mice developed such
thrombus. Active immunization with prothrombin or beta2GPI/prothrombin
is associated with prothrombotic activity of blood in an ex-vivo model.
This is the first direct evidence for thrombus induction by aPT