Background: Protein S (PS) is a natural anticoagulant acting as a cofactor for activated protein C (APC) in the proteolytic inactivation of activated factors V (FVa) and VIII (FVIIIa), but also for tissue factor pathway inhibitor α (TFPIα) in the inhibition of activated factor X (FXa).
Objective: For therapeutic purposes, we aimed at generating single-domain antibodies (sdAbs) that could specifically modulate the APC-cofactor activity of PS in vivo.
Methods: A llama-derived immune library of sdAbs was generated and screened on recombinant human PS by phage display.
Alpha-macroglobulin (αM) is a physiological macromolecule that facilitates the clearance of many proteinases, cytokines and growth factors in human. Here, we explored the effect of induced forms of αM on anticoagulant drugs. Gla-domainless factor Xa (GDFXa) and methylamine (MA)-induced αM were prepared and characterized by electrophoresis, immunonephelometry, chromogenic, clot waveform and rotational thromboelastometry assays.
View Article and Find Full Text PDFInherited protein C (PC) deficiency caused by mutations in the gene is a well-known risk factor for venous thromboembolism. Few studies have investigated the relationship between genotype and plasma or clinical phenotypes. We addressed this issue in a large retrospective cohort of 1,115 heterozygous carriers of 226 pathogenic or likely pathogenic mutations.
View Article and Find Full Text PDFBackground: Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency.
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