Abstract
Aims
To explore the effect of intravenous tranexamic acid (IV-TXA) on inflammation and immune response following primary total knee arthroplasty (TKA).
Methods
Primary TKA patients (n = 125) were randomized into the following four groups: group A to receive placebo; group B to receive a single dose of 20 mg kg−1 IV-TXA and 20 mg of intravenous dexamethasone (IV-DXM); group C to receive six doses of IV-TXA (total dosage > 6 g); and group D to receive six doses of IV-TXA combined with three doses of IV-DXM (total dosage = 40 mg). The primary outcomes were C-reactive protein (CRP) and interleukin (IL)-6 levels and the secondary outcomes were complement C3 and C4 and T-cell subset levels, which were measured preoperatively and at 24 h, 48 h, 72 h, and 2 weeks postoperatively.
Results
The postoperative peak CRP and IL-6 levels in group C (93.7 ± 22.2 mg L−1, 108.8 ± 41.7 pg mL−1) were lower compared with those in group A (134.7 ± 28.8 mg L−1, P < 0.01; 161.6 ± 64.4 pg mL−1, P < 0.01). Groups B and D exhibited significantly lower CRP and IL-6 levels compared with groups A and C at 24 h, 48 h, and 72 h postoperatively (P < 0.05 for all). In group C, complement C3 and C4 levels were higher compared with those in group A at 48 h (0.967 ± 0.127 g L−1 vs. 0.792 ± 0.100 g L−1, P < 0.01; 0.221 ± 0.046 g L−1 vs. 0.167 ± 0.028 g L−1, P < 0.01) and 72 h (1.050 ± 0.181 g L−1 vs. 0.860 ± 0.126 g L−1, P = 0.01; 0.240 ± 0.052 g L−1 vs. 0.182 ± 0.036 g L−1, P < 0.01) postoperatively and CD3 and CD4 subset levels were higher compared with those in group B at 24 h postoperatively (66.78 ± 9.29% vs. 56.10 ± 12.47%, P < 0.05; 36.69 ± 5.78% vs. 28.39 ± 8.89%, P < 0.05).
Conclusion
Six doses of IV-TXA could attenuate the inflammatory effect, modulate the immune response, and reduce immunosuppression caused by DXM in patients after TKA.
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References
Amara U et al (2010) Molecular intercommunication between the complement and coagulation systems. J Immunol 185:5628–5636
Andersson L, Eriksson O, Hedlund PO, Kjellman H, Lindqvist B (1978) Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases. Urol Res 6:83–88
Barthel D, Schindler S, Zipfel PF (2012) Plasminogen is a complement inhibitor. J Biol Chem 287:18831–18842
Benoni G, Lethagen S, Fredin H (1997) The effect of tranexamic acid on local and plasma fibrinolysis during total knee arthroplasty. Thromb Res 85:195–206
Bian ZX, Shang HC (2011) CONSORT 2010 statement updated guidelines for reporting parallel group randomized trials. Ann Intern Med 154:290–291 (author reply 291–292)
Blanie A, Bellamy L, Rhayem Y, Flaujac C, Samama CM, Fontenay M, Rosencher N (2013) Duration of postoperative fibrinolysis after total hip or knee replacement: a laboratory follow-up study. Thromb Res 131:e6–e11
Borg RJ et al (2015) Dendritic cell-mediated phagocytosis but not immune activation is enhanced by plasmin. PLoS ONE 10:e0131216
Boudreau RM et al (2017) Impact of tranexamic acid on coagulation and inflammation in murine models of traumatic brain injury and hemorrhage. J Surg Res 215:47–54
Carter DW et al (2019) Tranexamic acid suppresses the release of mitochondrial DAMPs and reduces lung inflammation in a murine burn model. J Trauma Acute Care Surg 86:617–624
Draxler DF, Sashindranath M, Medcalf RL (2017) Plasmin: a modulator of immune function. Semin Thromb Hemost 43:143–153
Foley JH et al (2016) Complement activation in arterial and venous thrombosis is mediated by plasmin. EBioMedicine 5:175–182
Kehlet H (2013) Fast-track hip and knee arthroplasty. Lancet 381:1600–1602
Later AF, Sitniakowsky LS, van Hilten JA, van de Watering L, Brand A, Smit NP, Klautz RJ (2013) Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery. J Thorac Cardiovasc Surg 145(1611–1616):1616.e1611–1614
Levi M, van der Poll T, Buller HR (2004) Bidirectional relation between inflammation and coagulation. Circulation 109:2698–2704
Li X, Syrovets T, Genze F, Pitterle K, Oberhuber A, Orend KH, Simmet T (2010) Plasmin triggers chemotaxis of monocyte-derived dendritic cells through an Akt2-dependent pathway and promotes a T-helper type-1 response. Arterioscler Thromb Vasc Biol 30:582–590
McCormack PL (2012) Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs 72:585–617
Robertshaw HJ (2008) An anti-inflammatory role for tranexamic acid in cardiac surgery? Crit Care 12:105
Schuliga M (2015) The inflammatory actions of coagulant and fibrinolytic proteases in disease. Mediators Inflamm 2015:437695
Slade MS, Simmons RL, Yunis E, Greenberg LJ (1975) Immunodepression after major surgery in normal patients. Surgery 78:363–372
Syrovets T, Jendrach M, Rohwedder A, Schule A, Simmet T (2001) Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKbeta-mediated NF-kappaB activation. Blood 97:3941–3950
Szaba FM, Smiley ST (2002) Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood 99:1053–1059
Teng Y, Feng C, Liu Y, Jin H, Gao Y, Li T (2018) Anti-inflammatory effect of tranexamic acid against trauma-hemorrhagic shock-induced acute lung injury in rats. Exp Anim 67:313–320
Wang D et al (2018) The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial. J Thromb Haemost 16:2442–2453
World HO (2001) Iron deficiency anaemia: assessment prevention and control. A guide for programme managers, vol 21. WHO, Geneva
World MA (2013) World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310:2191–2194
Wu X, Dubick MA, Schwacha MG, Cap AP, Darlington DN (2017) Tranexamic acid attenuates the loss of lung barrier function in a rat model of polytrauma and hemorrhage with resuscitation. Shock 47:500–505
Xie J, Ma J, Yao H, Yue C, Pei F (2016) Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss after primary total knee arthroplasty without tourniquet: a randomized clinical trial. J Arthroplast 31:2458–2464
Xu B, Ma J, Huang Q, Huang ZY, Zhang SY, Pei FX (2018a) Two doses of low-dose perioperative dexamethasone improve the clinical outcome after total knee arthroplasty: a randomized controlled study. Knee Surg Sports Traumatol Arthrosc 26:1549–1556
Xu H, Zhang S, Xie J, Lei Y, Cao G, Pei F (2018b) Multiple doses of perioperative dexamethasone further improve clinical outcomes after total knee arthroplasty: a prospective, randomized, controlled study. J Arthroplast 33:3448–3454
Zeng WN, Liu JL, Wang FY, Chen C, Zhou Q, Yang L (2018) Low-dose epinephrine plus tranexamic acid reduces early postoperative blood loss and inflammatory response. J bone Jt Surg: Am 100:295–304
Zhang S, Huang Q, Xu B, Ma J, Cao G, Pei F (2018) Effectiveness and safety of an optimized blood management program in total hip and knee arthroplasty: a large, single-center, retrospective study. Medicine 97:e9429
Zhang S, Xie J, Cao G, Lei Y, Huang Q, Pei F (2019) Six-dose intravenous tranexamic acid regimen further inhibits postoperative fibrinolysis and reduces hidden blood loss following total knee arthroplasty. J Knee Surg. https://doi.org/10.1055/s-0039-1694768
Acknowledgements
The authors sincerely acknowledge the entire staffs of the Department of Orthopedic Surgery, West China Hospital, Sichuan University, who offered assistance in the coursing of this study. This study was funded by the National Health and Family Planning Commission of the People's Republic of China (CN) program (201302007). We thank Jodi Smith, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
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Zhang, S., Xu, H., Xie, J. et al. Tranexamic acid attenuates inflammatory effect and modulates immune response in primary total knee arthroplasty: a randomized, placebo-controlled, pilot trial. Inflammopharmacol 28, 839–849 (2020). https://doi.org/10.1007/s10787-020-00695-6
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DOI: https://doi.org/10.1007/s10787-020-00695-6