Skip to main content
Top
Published in: Journal of Orthopaedic Surgery and Research 1/2019

Open Access 01-12-2019 | Tranexamic Acid | Research article

Application of thrombelastography (TEG) for safety evaluation of tranexamic acid in primary total joint arthroplasty

Authors: Xiang-Dong Wu, Yu Chen, Mian Tian, Yao He, Yu-Zhang Tao, Wei Xu, Qiang Cheng, Cheng Chen, Wei Liu, Wei Huang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

Login to get access

Abstract

Background

Questions remain, mainly concerning whether tranexamic acid (TXA) is truly safe since all available trials were underpowered to identify clinically important differences. The objective of this study is to evaluate the safety of TXA by using a novel technique—thromboelastography (TEG).

Methods

A retrospective review was conducted on 359 consecutive patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) and received multiple-dose or single-dose of TXA at a tertiary academic center. TEG parameters, TEG coagulation status, conventional coagulation test parameters, and incidence of thrombotic events were used for safety evaluation.

Results

Compared with single-dose cohort, patients who received multiple-dose of TXA had consistent statistically significant shortened R times on post-operative day 1 (POD1) and POD3 in both THA (POD1: 4.06 ± 0.71 s versus 4.45 ± 1.28 s, P = 0.011; POD3: 4.36 ± 0.83 s versus 5.12 ± 1.64 s, P < 0.0001) and TKA (POD1: 3.90 ± 0.73 s versus 4.29 ± 0.92 s, P = 0.011; POD3: 4.24 ± 0.94 s versus 4.65 ± 1.07 s, P = 0.023), while the K, α-angle, and MA values were similar during the perioperative period. TEG coagulation status analysis indicated that patients were significantly (P = 0.003) more likely with hypercoagulable status during the course of multiple-dose TXA. Conventional coagulation test parameters were similar. Only one patient developed calf vein thrombosis in the multiple-dose cohort.

Conclusions

Multiple-dose of TXA was associated with aggravated hypercoagulable state when compared with single-dose of TXA, but this prothrombotic state does not provoke thrombosis when combined with appropriate anticoagulant therapy. Therefore, multiple-dose of TXA remains safe and could be recommended for clinical practice. Potential benefits and possible risks should be trade-off when considering increasing the dosage and frequency of TXA on the present basis.

Trial registration

Literature
1.
go back to reference Tan J, Chen H, Liu Q, Chen C, Huang W. A meta-analysis of the effectiveness and safety of using tranexamic acid in primary unilateral total knee arthroplasty. J Surg Res. 2013;184(2):880–7.PubMedCrossRef Tan J, Chen H, Liu Q, Chen C, Huang W. A meta-analysis of the effectiveness and safety of using tranexamic acid in primary unilateral total knee arthroplasty. J Surg Res. 2013;184(2):880–7.PubMedCrossRef
3.
go back to reference Yuan X, Li B, Wang Q, Zhang X. Comparison of 3 routes of administration of tranexamic acid on primary unilateral total knee arthroplasty: a prospective, randomized, controlled study. J Arthroplast. 2017;32(9):2738–43.CrossRef Yuan X, Li B, Wang Q, Zhang X. Comparison of 3 routes of administration of tranexamic acid on primary unilateral total knee arthroplasty: a prospective, randomized, controlled study. J Arthroplast. 2017;32(9):2738–43.CrossRef
4.
go back to reference Yi Z, Bin S, Jing Y, Zongke Z, Pengde K, Fuxing P. Tranexamic acid administration in primary total hip arthroplasty: a randomized controlled trial of intravenous combined with topical versus single-dose intravenous administration. J Bone Joint Surg Am. 2016;98(12):983–91.PubMedCrossRef Yi Z, Bin S, Jing Y, Zongke Z, Pengde K, Fuxing P. Tranexamic acid administration in primary total hip arthroplasty: a randomized controlled trial of intravenous combined with topical versus single-dose intravenous administration. J Bone Joint Surg Am. 2016;98(12):983–91.PubMedCrossRef
5.
go back to reference Hiippala S, Strid L, Wennerstrand M, Arvela V, Mäntylä S, Ylinen J, et al. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth. 1995;74(5):534–7.PubMedCrossRef Hiippala S, Strid L, Wennerstrand M, Arvela V, Mäntylä S, Ylinen J, et al. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth. 1995;74(5):534–7.PubMedCrossRef
6.
go back to reference Poeran J, Rasul R, Suzuki S, Danninger T, Mazumdar M, Opperer M, et al. Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety. BMJ. 2014;349:g4829.PubMedPubMedCentralCrossRef Poeran J, Rasul R, Suzuki S, Danninger T, Mazumdar M, Opperer M, et al. Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety. BMJ. 2014;349:g4829.PubMedPubMedCentralCrossRef
7.
go back to reference Hsu C, Lin P, Kuo F, Wang J. A regime of two intravenous injections of tranexamic acid reduces blood loss in minimally invasive total hip arthroplasty: a prospective randomised double-blind study. Bone Joint J. 2015;97(7):905–10.PubMedCrossRef Hsu C, Lin P, Kuo F, Wang J. A regime of two intravenous injections of tranexamic acid reduces blood loss in minimally invasive total hip arthroplasty: a prospective randomised double-blind study. Bone Joint J. 2015;97(7):905–10.PubMedCrossRef
8.
go back to reference Xie J, Ma J, Yao H, Yue C, Pei F. Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss after primary total knee arthroplasty without tourniquet: a randomized clinical trial. J Arthroplast. 2016;31(11):2458–64.CrossRef Xie J, Ma J, Yao H, Yue C, Pei F. Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss after primary total knee arthroplasty without tourniquet: a randomized clinical trial. J Arthroplast. 2016;31(11):2458–64.CrossRef
9.
go back to reference Fraval A, Effeney P, Fiddelaers L, Smith B, Towell B, Tran P. OBTAIN A: outcome benefits of tranexamic acid in hip arthroplasty. A randomized double-blinded controlled trial. J Arthroplasty. 2017;32(5):1516–9.PubMedCrossRef Fraval A, Effeney P, Fiddelaers L, Smith B, Towell B, Tran P. OBTAIN A: outcome benefits of tranexamic acid in hip arthroplasty. A randomized double-blinded controlled trial. J Arthroplasty. 2017;32(5):1516–9.PubMedCrossRef
10.
go back to reference Luo Z-Y, Wang H-Y, Wang D, Zhou K, Pei F-X, Zhou Z-K. Oral vs intravenous vs topical tranexamic acid in primary hip arthroplasty: a prospective, randomized, double-blind, controlled study. J Arthroplasty. 2018;33(3):786–93.PubMedCrossRef Luo Z-Y, Wang H-Y, Wang D, Zhou K, Pei F-X, Zhou Z-K. Oral vs intravenous vs topical tranexamic acid in primary hip arthroplasty: a prospective, randomized, double-blind, controlled study. J Arthroplasty. 2018;33(3):786–93.PubMedCrossRef
11.
go back to reference Lee SY, Chong S, Balasubramanian D, Na YG, Kim TK. What is the ideal route of administration of tranexamic acid in TKA? A randomized controlled trial. Clin Orthop Relat Res. 2017;475(8):1987–96.PubMedPubMedCentralCrossRef Lee SY, Chong S, Balasubramanian D, Na YG, Kim TK. What is the ideal route of administration of tranexamic acid in TKA? A randomized controlled trial. Clin Orthop Relat Res. 2017;475(8):1987–96.PubMedPubMedCentralCrossRef
12.
go back to reference Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, et al. The safety of tranexamic acid in total joint arthroplasty: a direct meta-analysis. J Arthroplasty. 2018;33(10):3070–82. e1PubMedCrossRef Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, et al. The safety of tranexamic acid in total joint arthroplasty: a direct meta-analysis. J Arthroplasty. 2018;33(10):3070–82. e1PubMedCrossRef
13.
go back to reference Wu X-D, Hu K-J, Sun Y-Y, Chen Y, Huang W. Letter to the editor on “The Safety of Tranexamic Acid in Total Joint Arthroplasty: a direct meta-analysis”. J Arthroplasty. 2018;33(10):3365–8. e1PubMedCrossRef Wu X-D, Hu K-J, Sun Y-Y, Chen Y, Huang W. Letter to the editor on “The Safety of Tranexamic Acid in Total Joint Arthroplasty: a direct meta-analysis”. J Arthroplasty. 2018;33(10):3365–8. e1PubMedCrossRef
14.
go back to reference Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, et al. Response to letter to the editor on “the safety of tranexamic acid in total joint arthroplasty: a direct meta-analysis”. J Arthroplast. 2018;33(10):3368–9.CrossRef Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, et al. Response to letter to the editor on “the safety of tranexamic acid in total joint arthroplasty: a direct meta-analysis”. J Arthroplast. 2018;33(10):3368–9.CrossRef
17.
go back to reference Agha RA, Borrelli MR, Vella-Baldacchino M, Thavayogan R, Orgill DP, STROCSS Group. The STROCSS statement: strengthening the reporting of cohort studies in surgery. Int J Surg. 2017;46:198–202. Agha RA, Borrelli MR, Vella-Baldacchino M, Thavayogan R, Orgill DP, STROCSS Group. The STROCSS statement: strengthening the reporting of cohort studies in surgery. Int J Surg. 2017;46:198–202.
18.
go back to reference Gu W-J, Gu X-P, Wu X-D, Chen H, Kwong JS, Zhou L-Y, et al. Restrictive versus liberal strategy for red blood-cell transfusion: a systematic review and meta-analysis in orthopaedic patients. J Bone Joint Surg Am. 2018;100(8):686–95.PubMedCrossRef Gu W-J, Gu X-P, Wu X-D, Chen H, Kwong JS, Zhou L-Y, et al. Restrictive versus liberal strategy for red blood-cell transfusion: a systematic review and meta-analysis in orthopaedic patients. J Bone Joint Surg Am. 2018;100(8):686–95.PubMedCrossRef
20.
go back to reference Zuckerman L, Cohen E, Vagher J, Woodward E, Caprini J. Comparison of thrombelastography with common coagulation tests. Thromb Haemost. 1981;46(4):752–6.PubMedCrossRef Zuckerman L, Cohen E, Vagher J, Woodward E, Caprini J. Comparison of thrombelastography with common coagulation tests. Thromb Haemost. 1981;46(4):752–6.PubMedCrossRef
21.
go back to reference Park MS, Martini WZ, Dubick MA, Salinas J, Butenas S, Kheirabadi BS, et al. Thromboelastography as a better indicator of postinjury hypercoagulable state than prothrombin time or activated partial thromboplastin time. J Trauma. 2009;67(2):266.PubMedPubMedCentralCrossRef Park MS, Martini WZ, Dubick MA, Salinas J, Butenas S, Kheirabadi BS, et al. Thromboelastography as a better indicator of postinjury hypercoagulable state than prothrombin time or activated partial thromboplastin time. J Trauma. 2009;67(2):266.PubMedPubMedCentralCrossRef
23.
24.
go back to reference Yang Y, Yao Z, Dai W, Shi P, Zhang C. Changes of thrombelastography in patients undergoing elective primary total knee and total hip replacement with low molecular heparin prophylaxis. J Orthop Surg Res. 2014;9(1):52.PubMedPubMedCentralCrossRef Yang Y, Yao Z, Dai W, Shi P, Zhang C. Changes of thrombelastography in patients undergoing elective primary total knee and total hip replacement with low molecular heparin prophylaxis. J Orthop Surg Res. 2014;9(1):52.PubMedPubMedCentralCrossRef
25.
go back to reference Jian C, Chen C, Dai Z, Hu N, Zhao C, Zhao Z, et al. Thromboelastography in assessment of blood coagulation function changes in perioperative patients undergoing arthroplasty. J Chongqing Med Univ. 2015;40:770–3. Jian C, Chen C, Dai Z, Hu N, Zhao C, Zhao Z, et al. Thromboelastography in assessment of blood coagulation function changes in perioperative patients undergoing arthroplasty. J Chongqing Med Univ. 2015;40:770–3.
26.
go back to reference Gonzalez E, Kashuk JL, Moore EE, Silliman CC. Differentiation of enzymatic from platelet hypercoagulability using the novel thrombelastography parameter delta (Δ). J Surg Res. 2010;163(1):96–101.PubMedPubMedCentralCrossRef Gonzalez E, Kashuk JL, Moore EE, Silliman CC. Differentiation of enzymatic from platelet hypercoagulability using the novel thrombelastography parameter delta (Δ). J Surg Res. 2010;163(1):96–101.PubMedPubMedCentralCrossRef
27.
go back to reference Thakur M, Ahmed AB. A review of thromboelastography. Int J Periop Ultrasound Appl Technol. 2012;1(1):25–9.CrossRef Thakur M, Ahmed AB. A review of thromboelastography. Int J Periop Ultrasound Appl Technol. 2012;1(1):25–9.CrossRef
28.
go back to reference Burdett H, Eaglestone E, Roberts P. The in vivo effects of tranexamic acid on the thromboelastogram. Eur J Anaesthesiol. 2002;19:13.CrossRef Burdett H, Eaglestone E, Roberts P. The in vivo effects of tranexamic acid on the thromboelastogram. Eur J Anaesthesiol. 2002;19:13.CrossRef
29.
go back to reference Kelmer E, Segev G, Papashvilli V, Rahimi-Levene N, Bruchim Y, Aroch I, et al. Effects of intravenous administration of tranexamic acid on hematological, hemostatic, and thromboelastographic analytes in healthy adult dogs. J Vet Emerg Crit Care (San Antonio). 2015;25(4):495–501.CrossRef Kelmer E, Segev G, Papashvilli V, Rahimi-Levene N, Bruchim Y, Aroch I, et al. Effects of intravenous administration of tranexamic acid on hematological, hemostatic, and thromboelastographic analytes in healthy adult dogs. J Vet Emerg Crit Care (San Antonio). 2015;25(4):495–501.CrossRef
30.
go back to reference Reed MR, Woolley LT. Uses of tranexamic acid. Continuing Education in Anaesthesia Critical Care & Pain. 2015;15(1):32–7.CrossRef Reed MR, Woolley LT. Uses of tranexamic acid. Continuing Education in Anaesthesia Critical Care & Pain. 2015;15(1):32–7.CrossRef
31.
go back to reference Ortmann E, Besser M, Klein A. Antifibrinolytic agents in current anaesthetic practice. Br J Anaesth. 2013;111(4):549–63.PubMedCrossRef Ortmann E, Besser M, Klein A. Antifibrinolytic agents in current anaesthetic practice. Br J Anaesth. 2013;111(4):549–63.PubMedCrossRef
32.
go back to reference Ogiwara K, Nogami K, Nishiya K, Shima M. Plasmin-induced procoagulant effects in the blood coagulation: a crucial role of coagulation factors V and VIII. Blood Coagul Fibrinolysis. 2010;21(6):568–76.PubMedCrossRef Ogiwara K, Nogami K, Nishiya K, Shima M. Plasmin-induced procoagulant effects in the blood coagulation: a crucial role of coagulation factors V and VIII. Blood Coagul Fibrinolysis. 2010;21(6):568–76.PubMedCrossRef
33.
go back to reference Nogami K, Shima M, Matsumoto T, Nishiya K, Tanaka I, Yoshioka A. Mechanisms of plasmin-catalyzed inactivation of factor VIII: a crucial role for proteolytic cleavage at Arg336 responsible for plasmin-catalyzed factor VIII inactivation. J Biol Chem. 2007;282(8):5287–95.PubMedCrossRef Nogami K, Shima M, Matsumoto T, Nishiya K, Tanaka I, Yoshioka A. Mechanisms of plasmin-catalyzed inactivation of factor VIII: a crucial role for proteolytic cleavage at Arg336 responsible for plasmin-catalyzed factor VIII inactivation. J Biol Chem. 2007;282(8):5287–95.PubMedCrossRef
35.
go back to reference Mezzano D, Panes O, Muñoz B, Pais E, Tagle R, González F, et al. Tranexamic acid inhibits fibrinolysis, shortens the bleeding time and improves platelet function in patients with chronic renal failure. Thromb Haemost. 1999;81(4):1250–4. Mezzano D, Panes O, Muñoz B, Pais E, Tagle R, González F, et al. Tranexamic acid inhibits fibrinolysis, shortens the bleeding time and improves platelet function in patients with chronic renal failure. Thromb Haemost. 1999;81(4):1250–4.
36.
go back to reference Šaboviã M, Zupan IP, Salobir B, Zupan I, Černelã P, Lavre J, et al. The effect of long term, low-dose tranexamic acid treatment on platelet dysfunction and haemoglobin levels in haemodialysis patients. Thromb Haemos. 2005;94(06):1245–50. Šaboviã M, Zupan IP, Salobir B, Zupan I, Černelã P, Lavre J, et al. The effect of long term, low-dose tranexamic acid treatment on platelet dysfunction and haemoglobin levels in haemodialysis patients. Thromb Haemos. 2005;94(06):1245–50.
37.
go back to reference Weber CF, Görlinger K, Byhahn C, Moritz A, Hanke AA, Zacharowski K, et al. Tranexamic acid partially improves platelet function in patients treated with dual antiplatelet therapy. Eur J Anaesthesiol. 2011;28(1):57–62.PubMedCrossRef Weber CF, Görlinger K, Byhahn C, Moritz A, Hanke AA, Zacharowski K, et al. Tranexamic acid partially improves platelet function in patients treated with dual antiplatelet therapy. Eur J Anaesthesiol. 2011;28(1):57–62.PubMedCrossRef
38.
go back to reference Shi J, Ji H, Ren F, Wang G, Xu M, Xue Y, et al. Protective effects of tranexamic acid on clopidogrel before coronary artery bypass grafting: a multicenter randomized trial. JAMA Surg. 2013;148(6):538–47.PubMedCrossRef Shi J, Ji H, Ren F, Wang G, Xu M, Xue Y, et al. Protective effects of tranexamic acid on clopidogrel before coronary artery bypass grafting: a multicenter randomized trial. JAMA Surg. 2013;148(6):538–47.PubMedCrossRef
39.
go back to reference Huang W, Xu LY, Shao SY, Yao L, Wang TB. Impact of hip fracture on coagulation function in elderly patients. Beijing Da Xue Xue Bao. 2013;45(5):742–4.PubMed Huang W, Xu LY, Shao SY, Yao L, Wang TB. Impact of hip fracture on coagulation function in elderly patients. Beijing Da Xue Xue Bao. 2013;45(5):742–4.PubMed
40.
go back to reference Carling MS, Jeppsson A, Eriksson BI, Brisby H. Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study. J Orthop Surg Res. 2015;10(1):48.PubMedPubMedCentralCrossRef Carling MS, Jeppsson A, Eriksson BI, Brisby H. Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study. J Orthop Surg Res. 2015;10(1):48.PubMedPubMedCentralCrossRef
41.
go back to reference Wu XD, Xiao PC, Zhu ZL, Liu JC, Li YJ, Huang W. The necessity of routine postoperative laboratory tests in enhanced recovery after surgery for primary hip and knee arthroplasty: a retrospective cohort study protocol. Medicine (Baltimore). 2019;98(18):e15513.CrossRef Wu XD, Xiao PC, Zhu ZL, Liu JC, Li YJ, Huang W. The necessity of routine postoperative laboratory tests in enhanced recovery after surgery for primary hip and knee arthroplasty: a retrospective cohort study protocol. Medicine (Baltimore). 2019;98(18):e15513.CrossRef
42.
go back to reference Sperzel M, Huetter J. Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost. 2007;5(10):2113–8.PubMedCrossRef Sperzel M, Huetter J. Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost. 2007;5(10):2113–8.PubMedCrossRef
Metadata
Title
Application of thrombelastography (TEG) for safety evaluation of tranexamic acid in primary total joint arthroplasty
Authors
Xiang-Dong Wu
Yu Chen
Mian Tian
Yao He
Yu-Zhang Tao
Wei Xu
Qiang Cheng
Cheng Chen
Wei Liu
Wei Huang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-019-1250-6

Other articles of this Issue 1/2019

Journal of Orthopaedic Surgery and Research 1/2019 Go to the issue