Fig. 1.

Proposed mechanisms for cerebral sinus venous thrombosis in vaccine-induced immune thrombocytopenia (VITT). We proposed that venous thrombosis can be divided into two complementary and synergistic pathways in VITT. First, circulating PF4 antibodies complexes bind platelets and monocytic FcγRIIA receptors, causing cell activation and release of procoagulant microparticles (MPs). Second, the endothelium is directly activated by PF4 antibodies complexes and expresses the adhesion proteins E-selectin P-selectin and von Willebrand factor (VWF). Circulating TF+/MPs, PF4+/TF+/MPs, platelets and leukocytes bind to the activated endothelium and lead to the activation of the coagulation cascade. Cerebral sinus venous thrombosis in VITT is likely the consequence of (i) the key role played by circulating TF in venous thrombosis unrelated to vessel damage and (ii) the key role of endothelial cell-associated TF pathway in cerebral microvascular thrombogenesis. MPs microparticles, PF4 platelet factor 4, TF tissue factor, VWF Von Willebrand factor