The Immunomodulatory Effect of Antrifibrinolytic (Tranexamic Acid) in Total Knee Arthroplasty

Summary

The administration of the tranexamic acid (TRAXA), an antifibrinolytic, blocks primary fibrinolysis, and thus the haemorrhage, in the early postoperative period. Significant surgical operations, as well as trauma, initiate a similar dynamic homeostatic mechanism between the creation of a clot (primary and secondary haemostasis) and its dissolution (fibrinolysis). Antifibrinolytics have been proven effective in reducing haemorrhage in patients who have undergone significant surgical operations with normal fibrinolysis, with the use of an appropriate surgical technique. A pharmacokinetic study has shown that peak fibrinolytic activity is present for 6 hours after the incision and it persists for 18 hours in total knee and hip arthroplasty. The administration of the tranexamic acid in optional orthopaedic surgery of total hip (THA) and knee (TKA) arthroplasty reduces the postoperative haemorrhage, as well as the number and volume of the postoperative autologous blood. A trauma in the organism triggers the immunologic response. New term has been introduced - the post-traumatic immunosuppression (PTI), characterised by: a change on the immunologic cells (neutrophilia, monocytosis, increased number of mesenchymal stromal cells, reduced expression of HLA-DR on monocytes, reduced function of natural killer (NK) cells, increased lymphocyte apoptosis, a shift in homoeostasis towards the Th2 phenotype facilitated by Treg lymphocytes - CD4+CD25+CD127-); a change in production levels of various cytokines (anti-inflammatory cytokines): IL-10, IL-4; anti- and pro-inflammatory cytokine: IL-6; pro-inflammatory cytokines IL-2, TNF-α, IFN-γ); the activation of the complement system (C5a and C3a via factor VII - tissue factor system, activated by cell damage). Post-traumatic immunosuppression can be made worse by transfusion, haemorrhage, stress, significant surgical operation and immunosuppressive drugs. The research has shown that Treg lymphocytes CD4+CD25+CD127- have an important role in controlling the acquired and innate immunity (comprising 6-8% of all CD4+ lymphocytes). Stopping haemorrhage prevents the occurrence of anaemia, as well as the need for transfusion of blood products, which lead to developing the post-traumatic immunosuppression (PTI).

Timeline

Start

2018-12-18

Primary completion

2019-12

Completion

2019-12

Publications

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• Background Seddiki N, Santner-Nanan B, Martinson J, Zaunders J, Sasson S, Landay A, Solomon M, Selby W, Alexander SI, Nanan R, Kelleher A, Fazekas de St Groth B. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med. 2006 Jul 10;203(7):1693-700. doi: 10.1084/jem.20060468. Epub 2006 Jul 3.
• Background Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohe J, Lepape A, Ayala A, Monneret G. Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009 Apr;35(4):678-86. doi: 10.1007/s00134-008-1337-8. Epub 2008 Oct 23.
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• Background Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL, Thornton AM. The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol Rev. 2006 Aug;212:60-73. doi: 10.1111/j.0105-2896.2006.00415.x.
• Background Hartigan-O'Connor DJ, Poon C, Sinclair E, McCune JM. Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells. J Immunol Methods. 2007 Jan 30;319(1-2):41-52. doi: 10.1016/j.jim.2006.10.008. Epub 2006 Nov 3.
• Background Fragkou PC, Torrance HD, Pearse RM, Ackland GL, Prowle JR, Owen HC, Hinds CJ, O'Dwyer MJ. Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study. Crit Care. 2014 Oct 1;18(5):541. doi: 10.1186/s13054-014-0541-x.
• Results Blanie A, Bellamy L, Rhayem Y, Flaujac C, Samama CM, Fontenay M, Rosencher N. Duration of postoperative fibrinolysis after total hip or knee replacement: a laboratory follow-up study. Thromb Res. 2013 Jan;131(1):e6-e11. doi: 10.1016/j.thromres.2012.11.006. Epub 2012 Nov 26.

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