2. Academic Validation
  3. Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis

Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis

  • J Thromb Haemost. 2019 Dec;17(12):2174-2187. doi: 10.1111/jth.14603.
Dominik F Draxler 1,  Maria Daglas 1,  Anushka Fernando 1,  Gryselda Hanafi 1,  Fiona McCutcheon 1,  Heidi Ho 1,  Adam Galle 1,  Julia Gregory 1,  Pia Larsson 1,  Charithani Keragala 1,  David K Wright 2 3,  Elnaz Tavancheh 1,  Amanda E Au 1,  Be'eri Niego 1,  Kirsty Wilson 4,  Magdalena Plebanski 4 5,  Maithili Sashindranath 1,  Robert L Medcalf 1
Affiliations

Affiliations

  • 1 Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
  • 2 Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
  • 3 The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
  • 4 Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia.
  • 5 School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
PMID: 31393041 DOI: 10.1111/jth.14603
Abstract

Background: Traumatic brain injury (TBI) is known to promote immunosuppression, making patients more susceptible to Infection, yet potentially exerting protective effects by inhibiting central nervous system (CNS) reactivity. Plasmin, the effector protease of the fibrinolytic system, is now recognized for its involvement in modulating immune function.

Objective: To evaluate the effects of plasmin and tranexamic acid (TXA) on the immune response in wild-type and plasminogen-deficient (plg-/- ) mice subjected to TBI.

Methods: Leukocyte subsets in lymph nodes and the brain in mice post TBI were evaluated by flow cytometry and in blood with a hemocytometer. Immune responsiveness to CNS antigens was determined by Enzyme-linked Immunosorbent Spot (ELISpot) assay. Fibrinolysis was determined by thromboelastography and measuring D-dimer and plasmin-antiplasmin complex levels.

Results: Plg-/- mice, but not plg+/+ mice displayed increases in both the number and activation of various antigen-presenting cells and T cells in the cLN 1 week post TBI. Wild-type mice treated with TXA also displayed increased cellularity of the cLN 1 week post TBI together with increases in innate and adaptive immune cells. These changes occurred despite the absence of systemic hyperfibrinolysis or coagulopathy in this model of TBI. Importantly, neither plg deficiency nor TXA treatment enhanced the autoreactivity within the CNS.

Conclusion: In the absence of systemic hyperfibrinolysis, plasmin deficiency or blockade with TXA increases migration and proliferation of conventional dendritic cells (cDCs) and various antigen-presenting cells and T cells in the draining cervical lymph node (cLN) post TBI. Tranexamic acid might also be clinically beneficial in modulating the inflammatory and immune response after TBI, but without promoting CNS autoreactivity.

Keywords

fibrinolysis; immunosuppression; plasminogen; tranexamic acid; traumatic brain injury.

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