Leukocyte-released enzymes and DAMPs interact with components of the coagulation cascade. CF-DNA, histones, MMP, cathepsin G, and/or elastase modulate the traditional coagulation cascade by facilitating the activation of zymogen coagulation and fibrinolytic factors, and inhibiting the activity of endogenous anticoagulants. TF expressed by circulating leukocytes can activate coagulation through the extrinsic pathway, whereas monocyte-derived uPA can modulate fibrinolysis. CF-DNA, cell-free DNA; MMP, matrix metalloproteinase; PAI, plasminogen activator inhibitor; uPA, urokinase-type plasminogen activator.