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 pa...

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Veröffentlicht in:British journal of haematology 2005-04, Vol.129 (2), p.240-247
Hauptverfasser: Galli, Monica, Willems, George M., Rosing, Jan, Janssen, Rita M., Govers‐Riemslag, José W. P., Comfurius, Paul, Barbui, Tiziano, Zwaal, Robert F. A., Bevers, Edouard M.
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container_end_page 247
container_issue 2
container_start_page 240
container_title British journal of haematology
container_volume 129
creator Galli, Monica
Willems, George M.
Rosing, Jan
Janssen, Rita M.
Govers‐Riemslag, José W. P.
Comfurius, Paul
Barbui, Tiziano
Zwaal, Robert F. A.
Bevers, Edouard M.
description 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.
doi_str_mv 10.1111/j.1365-2141.2005.05438.x
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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 &gt;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. 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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 &gt;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. 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A.</au><au>Bevers, Edouard M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti‐prothrombin IgG from patients with anti‐phospholipid antibodies inhibits the inactivation of factor Va by activated protein C</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2005-04</date><risdate>2005</risdate><volume>129</volume><issue>2</issue><spage>240</spage><epage>247</epage><pages>240-247</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>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 &gt;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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15813852</pmid><doi>10.1111/j.1365-2141.2005.05438.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Antibodies, Antiphospholipid - immunology
Antiphospholipid Syndrome - immunology
anti‐phospholipid syndrome
anti‐prothrombin antibodies
Biological and medical sciences
Case-Control Studies
factor Va
Factor Va - immunology
Female
Hematologic and hematopoietic diseases
Hematology
Humans
Immunoglobulin G - blood
Lupus Coagulation Inhibitor - immunology
Lupus Erythematosus, Systemic - immunology
Male
Medical sciences
Platelet diseases and coagulopathies
protein C
Protein C - immunology
Prothrombin - immunology
Stroke - immunology
thrombosis
Venous Thrombosis - immunology
title Anti‐prothrombin IgG from patients with anti‐phospholipid antibodies inhibits the inactivation of factor Va by activated protein C
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