Neutrophil α-defensin-1 as a central mediator of thrombus formation. Abu-Fanne et al demonstrated that the contact activation factors kallikrein and FXIIa induce azurophil granule release from neutrophils, increasing plasma concentrations of the microbicidal peptide α-defensin-1 (α-def-1); this process was inhibited by aprotinin, corn trypsin inhibitor (CTI), or colchicine. Their study shows that α-defensin-1 promotes fibrin formation by thrombin, modifies fibrin morphology, and through its incorporation into the clot, inhibits tissue-type plasminogen activator (tPA)-mediated fibrinolysis. Consequently, α-defensin-1 increases thrombosis in vivo. In mice transgenic for human α-defensin-1, heparin showed greatly reduced antithrombotic potency, but when colchicine was used to inhibit α-defensin-1 release, heparin’s normal antithrombotic potency was restored. FDP, fibrin degradation products; PK, prekallikrein.