Total Plasma Protein S Is a Prothrombotic Marker in People Living With HIV.
J Acquir Immune Defic Syndr
; 90(4): 463-471, 2022 08 01.
Article
en En
| MEDLINE
| ID: mdl-35616596
ABSTRACT
BACKGROUND:
HIV-1 infection is associated with multiple procoagulant changes and increased thrombotic risk. Possible mechanisms for this risk include heigthened expression of procoagulant tissue factor (TF) on circulating monocytes, extracellular vesicles, and viral particles and/or acquired deficiency of protein S (PS), a critical cofactor for the anticoagulant protein C (PC). PS deficiency occurs in up to 76% of people living with HIV-1 (PLWH). As increased ex vivo plasma thrombin generation is a strong predictor of mortality, we investigated whether PS and plasma TF are associated with plasma thrombin generation.METHODS:
We analyzed plasma samples from 9 healthy controls, 17 PLWH on first diagnosis (naive), and 13 PLWH on antiretroviral therapy (ART). Plasma thrombin generation, total and free PS, PC, C4b-binding protein, and TF activity were measured.RESULTS:
We determined that the plasma thrombin generation assay is insensitive to PS, because of a lack of PC activation, and developed a modified PS-sensitive assay. Total plasma PS was reduced in 58% of the naive and 38% of the ART-treated PLWH samples and correlated with increased thrombin generation in the modified assay. Conversely, plasma TF was not increased in our patient population, suggesting that it does not significantly contribute to ex vivo plasma thrombin generation.CONCLUSION:
These data suggest that reduced total plasma PS contributes to the thrombotic risk associated with HIV-1 infection and can serve as a prothrombotic biomarker. In addition, our refined thrombin generation assay offers a more sensitive tool to assess the functional consequences of acquired PS deficiency in PLWH.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
4_TD
Problema de salud:
2_enfermedades_transmissibles
/
4_aids
Asunto principal:
Infecciones por VIH
/
Proteína S
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Acquir Immune Defic Syndr
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2022
Tipo del documento:
Article