Activated leukocytes, principally monocytes, and neutrophils, upregulate TF in response to proinflammatory cytokines, predominantly IL-6, and subsequently act to enhance coagulation.101,102 Additionally, monocytes provide a major source of intravascular TF by way of monocyte-derived, TF-bearing microvesicles.103,104 The major danger-associated molecular pattern, HMGB (high mobility group box protein)-1 released by platelets during inflammation has also been shown to be modified by leukocytes, thus facilitating its ability to co-ordinate thrombosis.105 Indeed, platelet-derived HMGB-1 is oxidized by activated monocyte-derived reactive oxygen species, thereby imparting HMGB-1s prothrombotic potential acting in a paracrine fashion to enhance platelet activation, monocyte TF expression and NET formation, and ultimately thrombin generation.105 Interestingly, it has been highlighted that type 1 interferons, a key family of widely expressed cytokines required for the co-ordinated innate immune response to bacterial and viral pathogens, enhance the release of HMBG1 thus enhancing the procoagulant activity of TF.106