THBD and Disseminated intravascular coagulation: Macrophage-derived HMGB1, a pro-nociceptive molecule of damage-associated molecular patterns (DAMPs), can be degraded by the endothelial thrombomodulin/thrombin system, an effect mimicked by recombinant human soluble thrombomodulin, known as thrombomodulin alfa (TMα; ART-1213, Recomodulin®), which has been approved as a therapeutic medicine for treatment of disseminated intravascular coagulation (DIC) in Japan [42,44].