The tissue factor pathway mediates both activation of coagulation and coagulopathy after injury

The Journal of Trauma and Acute Care Surgery
Benjamin M HowardMitchell Jay Cohen

Abstract

The initiation of coagulation in trauma is thought to originate from exposed tissue factor (TF); recent data have led to the alternative hypothesis that damage-associated molecular patterns may contribute to postinjury coagulation. In acute traumatic coagulopathy, aberrant coagulation is mediated via the activated protein C (aPC) pathway; the upstream regulators of this process and its relation to TF remain uncharacterized. To examine the role of the TF pathway in mediating acute traumatic coagulopathy, we used specific antibody blockades in an established murine model of traumatic hemorrhagic shock, hypothesizing that both coagulation activation after injury and aPC-mediated coagulopathy are driven by TF via thrombin. Mice underwent an established model of trauma and hemorrhage and were subjected to either sham (vascular cannulation) or trauma-hemorrhage (cannulation, laparotomy, shock to mean arterial pressure of 35 mm Hg); they were monitored for 60 minutes before sacrifice. Mice in each group were pretreated with either targeted anti-TF antibody to block the TF pathway or hirudin for specific blockade of thrombin. Plasma was assayed for thrombin-antithrombin (TAT) and aPC by enzyme-linked immunosorbent assay. Compared with ...Continue Reading

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Citations

Mar 21, 2017·Anesthesia and Analgesia·Jerrold H LevySibylle Kozek-Langenecker
Mar 25, 2017·The Journal of Trauma and Acute Care Surgery·S Ariane ChristieMitchell Jay Cohen
Dec 3, 2016·The Journal of Trauma and Acute Care Surgery·Ryan C KunitakeRachael A Callcut
Jan 5, 2020·Dental Traumatology : Official Publication of International Association for Dental Traumatology·Lucimar RodriguesJoão Gualberto C Luz
Dec 21, 2019·World Journal of Emergency Surgery : WJES·Cedric GangloffKarine Pichavant-Rafini

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