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The primary function of the coagulation cascade is to promote hemostasis and limit blood loss in response to tissue injury. In addition, there is now considerable evidence that coagulation plays pivotal roles in orchestrating inflammatory and tissue repair responses via both the generation of fibrin and activation of the family of proteinase-activated receptors (PARs). Consequently, uncontrolled coagulation and PAR signaling responses have been shown to contribute to excessive inflammatory and fibroproliferative responses in the context of a broad range of conditions, including acute lung injury and fibrotic lung disease. In terms of the cellular origin of excessive coagulation activity in the context of lung injury, coagulation zymogens are principally thought to be derived from the circulation and locally activated via the extrinsic tissue factor–dependent coagulation pathway within the intraalveolar compartment. More …