Anti‐prothrombin IgG from patients with anti‐phospholipid antibodies inhibits the inactivation of factor Va by activated protein C

Summary 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 CaCl2. 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.