Anti-ß2-glycoprotein I and anti-prothrombin antibodies cause lupus anticoagulant through different mechanisms of action.
J Thromb Haemost
; 19(4): 1018-1028, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33421291
ABSTRACT
BACKGROUND:
The presence of lupus anticoagulant (LA) is an independent risk factor for thrombosis. This laboratory phenomenon is detected as a phospholipid-dependent prolongation of the clotting time and is caused by autoantibodies against beta2-glycoprotein I (ß2GPI) or prothrombin. How these autoantibodies cause LA is unclear.OBJECTIVE:
To elucidate how anti-ß2GPI and anti-prothrombin antibodies cause the LA phenomenon.METHODS:
The effects of monoclonal anti-ß2GPI and anti-prothrombin antibodies on coagulation were analyzed in plasma and with purified coagulation factors.RESULTS:
Detection of LA caused by anti-ß2GPI or anti-prothrombin antibodies required the presence of the procofactor factor V (FV) in plasma. LA effect disappeared when FV was replaced by activated FV (FVa), both in a model system and in patient plasma, although differences between anti-ß2GPI and anti-prothrombin antibodies were observed. Further exploration of the effects of the antibodies on coagulation showed that the anti-ß2GPI antibody attenuated FV activation by activated faxtor X (FXa), whereas the anti-prothrombin antibody did not. Binding studies showed that ß2GPI--antibody complexes directly interacted with FV with high affinity. Anti-prothrombin complexes caused the LA phenomenon through competition for phospholipid binding sites with coagulation factors as reduced FXa binding to lipospheres was observed with flow cytometry in the presence of these antibodies.CONCLUSION:
Anti-ß2GPI and anti-prothrombin antibodies cause LA through different mechanisms of action While anti-ß2GPI antibodies interfere with FV activation by FXa through a direct interaction with FV, anti-prothrombin antibodies compete with FXa for phospholipid binding sites. These data provide leads for understanding the paradoxical association between thrombosis and a prolonged clotting time in the antiphospholipid syndrome.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidor de Coagulação do Lúpus
/
Síndrome Antifosfolipídica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda