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: Monica Galli, George M Willems, Jan Rosing, Rita M Janssen, José W P Govers-Riemslag, Paul Comfurius, Tiziano Barbui, Robert F A Zwaal, Edouard M Bevers
• Journal: British journal of haematology (Br J Haematol) Vol. 129 Issue 2 Pg. 240-7 (Apr 2005) ISSN: 0007-1048 [Print] England
• PMID: 15813852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Antiphospholipid
• Immunoglobulin G
• Lupus Coagulation Inhibitor
• Protein C
• Factor Va
• Prothrombin

Topics

• Antibodies, Antiphospholipid (immunology)
• Antiphospholipid Syndrome (immunology)
• Case-Control Studies
• Factor Va (immunology)
• Female
• Humans
• Immunoglobulin G (blood)
• Lupus Coagulation Inhibitor (immunology)
• Lupus Erythematosus, Systemic (immunology)
• Male
• Protein C (immunology)
• Prothrombin (immunology)
• Stroke (immunology)
• Venous Thrombosis (immunology)