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The effects of phosphatidylserine-dependent antiprothrombin antibody on thrombin generation

Arthritis and Rheumatism, ISSN: 0004-3591, Vol: 60, Issue: 8, Page: 2457-2467
2009
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Article Description

Objective. Antibodies to prothrombin (APTs) and to β- glycoprotein I are the major autoantibodies responsible for lupus anticoagulant (LAC) activity. APTs comprise antibodies against prothrombin alone as well as antibodies against phosphatidylserine/prothrombin complex (anti-PS/PT), the latter being highly associated with the antiphospholipid syndrome (APS). The effect of anti-PS/PT on thrombin generation has not been elucidated, and the paradoxical effect of LAC (an anticoagulant in vitro, but a procoagulant in vivo) remains an enigma. The purpose of this study was to investigate the effects of anti-PS/PT on thrombin generation and to examine the LAC paradox. Methods. We evaluated 36 anti-PS/PT-positive APS patients and 127 healthy subjects. Markers of in vivo thrombin/fibrin generation, including prothrombin fragment F, thrombin-antithrombin III complex, soluble fibrin monomer, D-dimer, and fibrin degradation products, were measured. Mouse monoclonal anti-PS/PT antibody 231D was established, and its effects on in vitro thrombin generation were investigated by chromogenic assay. Results. Significantly elevated levels of markers of thrombin/fibrin generation were observed in anti-PS/ PT-positive patients, regardless of the presence or absence of anticardiolipin antibodies, as compared with healthy subjects. In the presence of low concentrations of human activated factor V (FVa), monoclonal antibody 231D increased thrombin generation in a dose-dependent manner. In contrast, when high concentrations of FVa were added, monoclonal antibody 231D decreased thrombin generation. Under a constant concentration of FVa, a high concentration of human FXa enhanced the effect of 231D. Conclusion. The presence of anti-PS/PT greatly correlated with increased thrombin generation in APS patients. The in vitro effects of monoclonal antibody 231D on thrombin generation are "biaxial" according to the FVa/FXa balance. These data may serve as a clue to understanding the LAC paradox and the thrombogenic properties of anti-PS/PT. © 2009, American College of Rheumatology.

Bibliographic Details

Sakai, Yoshie; Atsumi, Tatsuya; Ieko, Masahiro; Amengual, Olga; Furukawa, Shin; Furusaki, Akira; Bohgaki, Miyuki; Kataoka, Hiroshi; Horita, Tetsuya; Yasuda, Shinsuke; Koike, Takao

Wiley

Medicine; Immunology and Microbiology

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