OVID-Studie: primäre Thromboseprophylaxe bei ambulanten Patienten mit SARS-CoV-2-Infektion

Die vor Kurzem begonnene OVID-Studie mit Beteiligung der Schweizer Universitätsspitäler und des Tessins hat zum Ziel, die Wirksamkeit und Sicherheit von Enoxaparin zur Vermeidung von Thrombosen bei ambulanten Patienten mit SARS-CoV-2 zu untersuchen. Informationen zu Studie und Rekrutierung von Studienteilnehmenden sind im Folgenden aufgeführt

Soluble CD40 ligand induces β(3) integrin tyrosine phosphorylation and triggers platelet activation by outside-in signaling

We earlier reported that the soluble form of the CD40 ligand (sCD40L), is involved in thrombosis by stabilizing platelet thrombi. In this article, we have determined the mechanism by which this protein affects platelet biology. Addition of sCD40L to washed platelets was found to activate the receptor function of α(IIb)β(3) as measured by the induction of fibrinogen binding and the formation of platelet microparticles. Mutation in the KGD sequence (D117E) of sCD40L, the α(IIb)β(3)-binding domain in the N terminus of the protein resulted in a loss of the platelet-stimulatory activity of this protein. Integrilin, a α(IIb)β(3) antagonist, but not an antibody to CD40 that blocked the ligand-binding activity, inhibited these platelet-stimulatory events. CD40(-/-) platelets bound fibrinogen and formed microparticles similar to WT platelets, again indicating that CD40 is not involved in sCD40L-induced platelet activation. Exposure of platelets to sCD40L, but not D117E-sCD40L-coated surfaces, induced platelet thrombi formation under arterial shear rate. sCD40L-induced platelet stimulation resulted in the phosphorylation of tyrosine-759 in the cytoplasmic domain of β(3). Platelets from the diYF mouse strain, expressing β(3) in which both cytoplasmic tyrosines are mutated to phenylalanine, were defective in sCD40L-induced platelet stimulation. These data indicate that sCD40L is a primary platelet agonist and that platelet stimulation is induced by the binding of the KGD domain of sCD40L to α(IIb)β(3), triggering outside-in signaling by tyrosine phosphorylation of β(3)