A new pro-thrombotic mechanism of neutrophil extracellular traps in antiphospholipid syndrome: impact on activated protein C resistance.
Rheumatology (Oxford)
; 61(7): 2993-2998, 2022 07 06.
Article
em En
| MEDLINE
| ID: mdl-34791113
ABSTRACT
OBJECTIVES:
In APS, precise evaluation of thrombotic risk is a major challenge. Different players, such as activated protein C (APC) resistance or neutrophil extracellular traps (NETs) contribute to the risk of thrombosis. Nevertheless, no study has investigated the interaction between these actors. The main objective of this study was to investigate the relation between NETs and APC resistance.METHODS:
We designed a cross-sectional study including APS/antiphospholipid antibodies (aPL) patients and patients with autoimmune diseases (AID). We performed thrombin generation tests without and with APC to determine APC resistance. To evaluate circulating NETs, we measured plasma levels of MPO-DNA complexes and cell-free DNA with ELISA.RESULTS:
We recruited 117 patients with definite APS/aPL or AID. We found a positive correlation between NETs and APC resistance, in APS patients and specifically in patients with high thrombotic risk, displaying LA or positivity of all three aPL tests (triple+), or anti-domain I IgG (aDI+). All these patient subgroups had increased NETs concentrations and APC resistance. As the risk profile for thrombosis increased, the relationship between NETs and APC resistance was stronger.CONCLUSION:
We have shown that NETs participate in the hypercoagulable state of APS patients by contributing to APC resistance, in particular in high-risk patients. In these most at-risk patients, a targeted action on NETs could reduce APC resistance and constitute a new therapeutic approach in the treatment of APS patients in addition to antithrombotic therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose
/
Síndrome Antifosfolipídica
/
Resistência à Proteína C Ativada
/
Armadilhas Extracelulares
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Rheumatology (Oxford)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article