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Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent frequently used in elective surgery to reduce blood loss. We recently found it also acts as a potent immune-modulator in patients undergoing cardiac surgery. METHODS: Patients undergoing lower limb surgery were enrolled into the “Tranexa...

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Autores principales: Draxler, Dominik F., Hanafi, Gryselda, Zahra, Saffanah, McCutcheon, Fiona, Ho, Heidi, Keragala, Charithani B., Liu, Zikou, Daly, David, Painter, Thomas, Wallace, Sophia, Plebanski, Magdalena, Myles, Paul S., Medcalf, Robert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996554/
https://www.ncbi.nlm.nih.gov/pubmed/35410340
http://dx.doi.org/10.1186/s12959-022-00373-3
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author Draxler, Dominik F.
Hanafi, Gryselda
Zahra, Saffanah
McCutcheon, Fiona
Ho, Heidi
Keragala, Charithani B.
Liu, Zikou
Daly, David
Painter, Thomas
Wallace, Sophia
Plebanski, Magdalena
Myles, Paul S.
Medcalf, Robert L.
author_facet Draxler, Dominik F.
Hanafi, Gryselda
Zahra, Saffanah
McCutcheon, Fiona
Ho, Heidi
Keragala, Charithani B.
Liu, Zikou
Daly, David
Painter, Thomas
Wallace, Sophia
Plebanski, Magdalena
Myles, Paul S.
Medcalf, Robert L.
author_sort Draxler, Dominik F.
collection PubMed
description BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent frequently used in elective surgery to reduce blood loss. We recently found it also acts as a potent immune-modulator in patients undergoing cardiac surgery. METHODS: Patients undergoing lower limb surgery were enrolled into the “Tranexamic Acid in Lower Limb Arthroplasty” (TALLAS) pilot study. The cellular immune response was characterised longitudinally pre- and post-operatively using full blood examination (FBE) and comprehensive immune cell phenotyping by flowcytometry. Red blood cells and platelets were determined in the FBE and levels of T cell cytokines and the plasmin-antiplasmin complex determined using ELISA. RESULTS: TXA administration increased the proportion of circulating CD141+ conventional dendritic cells (cDC) on post-operative day (POD) 3. It also reduced the expression of CD83 and TNFR2 on classical monocytes and levels of circulating IL-10 at the end of surgery (EOS) time point, whilst increasing the expression of CCR4 on natural killer (NK) cells at EOS, and reducing TNFR2 on POD-3 on NK cells. Red blood cells and platelets were decreased to a lower extent at POD-1 in the TXA group, representing reduced blood loss. CONCLUSION: In this investigation we have extended our examination on the immunomodulatory effects of TXA in surgery by also characterising the end of surgery time point and including B cells and neutrophils in our immune analysis, elucidating new immunophenotypic changes in phagocytes as well as NK cells. This study enhances our understanding of TXA-mediated effects on the haemostatic and immune response in surgery, validating changes in important functional immune cell subsets in orthopaedic patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12959-022-00373-3.
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spelling pubmed-89965542022-04-12 Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery Draxler, Dominik F. Hanafi, Gryselda Zahra, Saffanah McCutcheon, Fiona Ho, Heidi Keragala, Charithani B. Liu, Zikou Daly, David Painter, Thomas Wallace, Sophia Plebanski, Magdalena Myles, Paul S. Medcalf, Robert L. Thromb J Research BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent frequently used in elective surgery to reduce blood loss. We recently found it also acts as a potent immune-modulator in patients undergoing cardiac surgery. METHODS: Patients undergoing lower limb surgery were enrolled into the “Tranexamic Acid in Lower Limb Arthroplasty” (TALLAS) pilot study. The cellular immune response was characterised longitudinally pre- and post-operatively using full blood examination (FBE) and comprehensive immune cell phenotyping by flowcytometry. Red blood cells and platelets were determined in the FBE and levels of T cell cytokines and the plasmin-antiplasmin complex determined using ELISA. RESULTS: TXA administration increased the proportion of circulating CD141+ conventional dendritic cells (cDC) on post-operative day (POD) 3. It also reduced the expression of CD83 and TNFR2 on classical monocytes and levels of circulating IL-10 at the end of surgery (EOS) time point, whilst increasing the expression of CCR4 on natural killer (NK) cells at EOS, and reducing TNFR2 on POD-3 on NK cells. Red blood cells and platelets were decreased to a lower extent at POD-1 in the TXA group, representing reduced blood loss. CONCLUSION: In this investigation we have extended our examination on the immunomodulatory effects of TXA in surgery by also characterising the end of surgery time point and including B cells and neutrophils in our immune analysis, elucidating new immunophenotypic changes in phagocytes as well as NK cells. This study enhances our understanding of TXA-mediated effects on the haemostatic and immune response in surgery, validating changes in important functional immune cell subsets in orthopaedic patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12959-022-00373-3. BioMed Central 2022-04-11 /pmc/articles/PMC8996554/ /pubmed/35410340 http://dx.doi.org/10.1186/s12959-022-00373-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Draxler, Dominik F.
Hanafi, Gryselda
Zahra, Saffanah
McCutcheon, Fiona
Ho, Heidi
Keragala, Charithani B.
Liu, Zikou
Daly, David
Painter, Thomas
Wallace, Sophia
Plebanski, Magdalena
Myles, Paul S.
Medcalf, Robert L.
Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
title Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
title_full Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
title_fullStr Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
title_full_unstemmed Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
title_short Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
title_sort tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996554/
https://www.ncbi.nlm.nih.gov/pubmed/35410340
http://dx.doi.org/10.1186/s12959-022-00373-3
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