title: Anti-prothrombin IgG from patients with anti-phospholipid antibodies inhibits the inactivation of factor Va by activated protein C.
abstract: Interference of anti-phospholipid antibodies with the protein C pathway has been suggested to play a role in the development of thrombosis in the anti-phospholipid syndrome. We studied the effect of IgG preparations containing anti-prothrombin antibodies of 17 lupus anticoagulant-positive patients and 12 controls on the inactivation of factor Va (FVa) by activated protein C (APC) in a system with purified coagulation factors. Test IgG was incubated with human prothrombin, phospholipid vesicles and CaCl(2). Protein S, FVa and APC were added and the APC-dependent loss of FVa activity was monitored over time. The residual amount of FVa remaining after 10 min was 14 +/- 4% (mean +/- SD) when 1.5 mg/ml normal IgG was present and ranged between 17% and 82% with 1.5 mg/ml patient IgG. Twelve patients IgG gave values of residual FVa >22% (i.e. 2 SD above the mean of controls), indicating that APC-mediated inactivation of FVa was significantly inhibited. The inhibition was strictly dependent on the presence of prothrombin, proportional to the concentration of IgG and strongly diminished at a 20-fold higher phospholipid concentration. Most, although not all, IgG containing anti-prothrombin antibodies inhibit the APC-catalysed FVa inactivation, which may contribute to the increased risk of thrombosis in patients with the anti-phospholipid syndrome.
authors.affiliation: Department of Haematology, Ospedali Riuniti, Bergamo, Italy. monicagalli@virgilio.it
authors.forename: Monica
authors.initials: M
authors.lastname: Galli
authors.forename: George M
authors.initials: GM
authors.lastname: Willems
authors.forename: Jan
authors.initials: J
authors.lastname: Rosing
authors.forename: Rita M
authors.initials: RM
authors.lastname: Janssen
authors.forename: José W P
authors.initials: JW
authors.lastname: Govers-Riemslag
authors.forename: Paul
authors.initials: P
authors.lastname: Comfurius
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Robert F A
authors.initials: RF
authors.lastname: Zwaal
authors.forename: Edouard M
authors.initials: EM
authors.lastname: Bevers
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D016022:Case-Control Studies; D015943:Factor Va / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016682:Lupus Coagulation Inhibitor / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D011486:Protein C / Q000276:immunology*; D011516:Prothrombin / Q000276:immunology*; D020521:Stroke / Q000276:immunology; D020246:Venous Thrombosis / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D011486:Protein C; D015943:Factor Va; D011516:Prothrombin