Exclusively, extracellular histone promote thrombi generation via platelet-dependent mechanisms (Fig. 3)232 by directly modulating the clotting properties of platelet-induced polyphosphate (polyP), allowing its induction of thrombi generation with histones.233 Moreover, histone enhance procoagulant phenotype of platelets by upregulation of P-selectin, phosphatidylserine (PS), and FV/Va, partially in a TLR2- and TLR4-dependent mechanism.232 The enhanced platelet aggregation might contribute to formation of platelet-rich thrombi in sepsis. The gene discussed is TLR4; the disease is Sepsis.