Rôle du facteur 4 plaquettaire dans la modulation de l'hémostase

Le facteur 4 plaquettaire (PF4) est un tétramère composé d'unités de 70 acides aminés contenu dans les granules a des plaquettes qui le sécrètent en grande quantité (10 à 25 g/ml) lors de l'activation. L'éventuelle fonction du PF4 dans l'hémostase reste ambiguë car des activités aussi bien pro- qu'anti-coagulantes lui ont été attribuées. Nous avons observé que le PF4 exerce un effet majeur sur la structure du caillot de fibrine. En étudiant la formation d'un caillot de fibrine en turbidimétrie et en microscopie électronique à balayage nous avons montré que le PF4 influence considérablement la polymérisation. Ainsi en se liant à la fibrine, le PF4 oriente l'assemblage des protofibrilles qui forment une nappe imperméable. Nous avons montré que le PF4 inhibait de façon dose-dépendante la génération de thrombine dans un plasma. Nous avons ègalement montré que le PF4 inhibe la formation du complexe prothrombinase en masquant le facteur V à son activateur, la thrombine. De façon surprenante, le PF4 s'est par ailleurs avéré être un puissant inhibiteur de l'agrégation plaquettaire. Nous proposons que le PF4, caractérisé par une très forte densité de charges positives, pourrait entrer en compétition avec la thrombine vis à vis des ligands de son exosite 1.Platelet factor 4 (PF4) is a tetrameric protein composed of four 70-amino-acid subunits that is contained in platelet a-granules. Large amounts of PF4 (up to 10-25 g/ml) are released upon platelet aggregation. The role of PF4 in hemostasis remains elusive as PF4 has been reported to possess procoagulant and anticoagulant activities as well. We have observed that PF4 exerts a major effect on the structure of the fibrin clot. By evaluating the formation of a fibrin clot by turbidimetric methods and by electronic microscopy, we have shown that PF4 has a considerable effect on the fibrin polymerization process. By binding to fibrin, PF4 thus drives the assembly of protofibrils which then form an impermeable network. In addition, we have demonstrated that PF4 dose-dependently inhibits the generation of thrombin in a plasma-based assay. Furthermore, we have shown that PF4 prevents the activation of factor V by thrombin, which results in inhibition of the prothrombinase complex. Surprisingly, PF4 is also a very potent inhibitor of platelet aggregation. We therefore propose that PF4, which contains a high density of positive charges exposed at its surface, might compete with thrombin towards various ligands of thrombin exosite 1, such as factor V, fibrinogen, PAR-1 (...).PARIS-BIUP (751062107) / SudocSudocFranceF

Equine Arteritis virus : epidemiology and viral characterization of European strains

International audienc

Development of a high- throughput cell-based assay to determine anti-equine arteritis virus properties of chemical compounds

International audienc

Development of a high- throughput cell-based assay to determine anti-equine arteritis virus properties of chemical compounds

International audienc

Benefit of endovascular thrombectomy for M2 middle cerebral artery occlusion in the ARISE II study.

BACKGROUND The benefit of endovascular thrombectomy for acute ischemic stroke with M2 segment middle cerebral artery occlusion remains controversial, with uncertainty and paucity of data specific to this population. OBJECTIVE To compare outcomes between M1 and M2 occlusions in the Analysis of Revascularization in Ischemic Stroke with EmboTrap (ARISE II) trial. METHODS We performed a prespecified analysis of the ARISE II trial with the primary outcome of 90-day modified Rankin Scale score of 0-2, which we termed good outcome. Secondary outcomes included reperfusion rates and major adverse events. The primary predictor was M2 occlusion, which we compared with M1 occlusion. RESULTS We included 183 patients, of whom 126 (69%) had M1 occlusion and 57 (31%) had M2 occlusion. There was no difference in the reperfusion rates or adverse events between M2 and M1 occlusions. The rate of good outcome was not different in M2 versus M1 occlusions (70.2% vs 69.7%, p=0.946). In a logistic regression model adjusted for age, sex, and baseline National Institutes of Health Stroke Scale score, M2 occlusions did not have a significantly different odds of good outcome compared with M1 occlusions (OR 0.94, 95% CI 0.47 to 1.88, p=0.87). CONCLUSION In ARISE II, M2 occlusions achieved a 70.2% rate of good outcome at 90 days, which is above published rates for untreated M2 occlusions and superior to prior reports of M2 occlusions treated with endovascular thrombectomy. We also report similar rates of good outcome, successful reperfusion, death, and other adverse events when comparing the M1 and M2 occlusions

A Diagnosis Can Hide Another: The Value of Brain Biopsy in Neurological Lesion of HIV Patients

International audienc