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Hypercoagulabilité associée aux anticorps anti-phospholipides : approches descriptives et mécanistiques

Abstract : The objective was to identify the mechanisms which contribute to the hypercoagulability associated with anti-phospholipid antibodies. Antibody-mediated platelet activation and interference of antibodies with phospholipid-dependent reactions were investigated. Murine monoclonal antibodies directed against ß2-glycoprotein I and prothrombin were used as model of anti-phospholipid antibodies. An anticoagulant effect, evidenced by impairment of thrombin generation and a procoagulant effect, by inhibition of activated protein C activity were shown. These phenomena occurs independently of platelet activation. The overall result was hypercoagulability. When immune-mediated platelet activation is sufficiently intense, it increases the amount of procoagulant phospholipids and antagonizes partially the anticoagulant effect of anti-phospholipid antibodies. Thus platelet activation contributes to reinforce the hypercoagulability due to activated protein C resistance. The antibody/antigen complexes interfere with pro- and anticoagulant complexes to the platelet surfaces. The avidity of each studied partners for the phospholipid surfaces take part in the mechanisms leading to hypercoagulability associated with antiphospholipid antibodies.
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Aurélie Membre. Hypercoagulabilité associée aux anticorps anti-phospholipides : approches descriptives et mécanistiques. Biologie cellulaire. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10125⟩. ⟨tel-01748518⟩

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