Effects of tranexamic acid on hidden blood loss after total knee arthroplasty in animal models

doi:10.3969/j.issn.2095-4344.2015.17.005

Abstract

Abstract:

BACKGROUND: Hidden blood loss leads to severe anemia after orthopedic joint arthroplasty. Blood transfusion is needed. Use of tranexamic acid can significantly decrease perioperative blood loss, reduce blood transfusion rate, however, mechanism of action of tranexamic acid on hidden blood loss and its relevance are not clear. OBJECTIVE: By establishing the rabbit models of total knee prosthesis, this study was designed to observe the variation of early preoperative blood loss with tranexamic acid, and to study the effects of tranexamic acid on hidden blood loss and its influence on deep venous thrombosis of lower limb.

METHODS: We designed the rabbit knee prosthesis ourselves. A total of 20 adult New Zealand rabbits were randomly divided into two groups, each group with 10 rabbits. Knee arthroplasty on the same side was performed. Experimental group received intravenous injection of 0.5 g 100 mL tranexamic acid at 15 minutes before replacement. Control group was given 100 mL sodium chloride at the same time. Blood was collected from all animals through ear vein at 1 day before replacement, 3, 6, 24, 48, 72 hours and 7 days after replacement. Blood routine examination and blood coagulation function test were conducted. The content of plasma D-Dimer was determined. Simultaneously, the operation time and intraoperative bleeding amount were recorded. After replacement, lower limb venous ultrasonography was performed.

RESULTS AND CONCLUSION: No significant difference in body weight, hemoglobin, hematocrit, and D-Dimer levels was detected between the two groups before replacement (P > 0.05). Significant differences in operation time and intraoperative dominant blood loss were detectable between the two groups (P < 0.05). Significant differences in hemoglobin and hematocrit were detected at 24 hours after replacement (P < 0.05), and these were better in the experimental group than in the control group. No significant difference in D-Dimer was observed between the two groups after replacement (P > 0.05). Operation time and intraoperative dominant blood loss were significantly associated with hemoglobin and hematocrit at 24 hours after replacement (P < 0.05). The changes in hemoglobin and hematocrit at 72 hours and 7 days after replacement were not apparently correlated with intraoperative D-Dimer changes. Obvious thrombus was not seen by lower limb venous ultrasonography after replacement. These results indicated that the use of tranexamic acid before total knee arthroplasty apparently reduced the intraoperative dominant blood loss, shortened operation time, and noticeably decreased hidden blood loss at 1 day after replacement, which was caused by the increased fibrinolysis with surgical stress, and did not apparently impact other hidden blood loss induced by other mechanism. Simultaneously, tranexamic acid is safe and reliable, and does not increase the risk of perioperative thrombus.

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

全文链接：

Key words: Arthroplasty, Replacement, Knee, Blood Loss, Surgical, Tranexamic Acid, Models, Animal

CLC Number:

R318

Yuan Lei, Bao Ni-rong, Zhao Jian-ning. Effects of tranexamic acid on hidden blood loss after total knee arthroplasty in animal models[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(17): 2648-2654.

Figures/Tables 6

References

[1]Fuqiang G, Wanshou G, Wei S, et al. Correlation between the coverage percentage of prosthesis and postoperative hidden blood loss in primary total knee arthroplasty. Chin Med J. 2014; 127(12): 2265-2269.
[2]Sehat KR, Evans RL, Newman JH. Hidden blood loss following hip and knee arthroplasty correct management of blood loss should take hidden loss into account. J Bone Joint Surg. 2004; 86(4):561-565.
[3]Shen H, Li Z, Feng M, et al. Analysis on hidden blood loss of total knee arthroplasty in treating knee osteoarthritis. Chin Medical J. 2011;124(11):1653.
[4]Benoni G, Lethagen S, Nilsson P, et al. Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty. Acta Orthop. 2000;71(3):250-254.
[5]Cid J, Lozano M. Tranexamic acid reduces allogeneic red cell transfusions in patients undergoing total knee arthroplasty: results of a meta-analysis of randomized controlled trials. Transfusion. 2005;45(8):1302-1307.
[6]Wong J, Abrishami A, El Beheiry H, et al. Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg Am 2010;92(15):2503.
[7]Ishida K，Tsumura N，Kitagawa A, et al. Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty. Int Orthop. 2011;35: 1639-1645.
[8]MacGillivray RG, Tarabichi SB, Hawari MF, et al. Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty: a prospective, randomized double blind study. J Arthroplasty. 2011;26(1): 24-28.
[9]Karam JA, Bloomfield MR, DiIorio TM, et al. Evaluation of the efficacy and safety of tranexamic acid for reducing blood loss in bilateral total knee arthroplasty. J Arthroplasty. 2014;29(3): 501-503.
[10]Iwai T, Tsuji S, Tomita T, et al. Repeat-dose intravenous tranexamic acid further decreases blood loss in total knee arthroplasty. Int Orthop. 2013;37(3): 441-445.
[11]Gandhi R, Evans H M, Mahomed S R, et al. Tranexamic acid and the reduction of blood loss in total knee and hip arthroplasty: a meta-analysis. BMC Res Notes. 2013;6(1): 184.
[12]Gillette BP, DeSimone LJ, Trousdale RT, et al. Low risk of thromboembolic complications with tranexamic acid after primary total hip and knee arthroplasty. Clin Orthop Relat Res 2013;471(1):150.
[13]Aguilera X, Martinez-Zapata MJ, Bosch A. Efficacy and safety of fibrin glue and tranexamic Acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. J Bone Joint Surg. 2013;95(22):2001-2007.
[14]Ma YQ, Zhang YC, Zhang H. [Local application of tranexamic acid reduces blood less in unilateral total knee arthroplasty: a retrospective comparason analysis]. Zhonghua Waike Zazhi. 2013;51(1):40-43.
[15]Vigna-Taglianti F, Basso L, Rolfo P, et al. Tranexamic acid for reducing blood transfusions in arthroplasty interventions: a cost-effective practice. Eur J Orthop Surg Traumatol. 2013: 1-7.
[16]Sarzaeem MM, Razi M, Kazemian G, et al. Comparing Efficacy of Three Methods of Tranexamic Acid Administration in Reducing Hemoglobin Drop Following Total Knee Arthroplasty. J Arthroplasty. 2014.
[17]Seo JG, Moon YW, Park SH, et al. The comparative efficacies of intra-articular and IV tranexamic acid for reducing blood loss during total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2013;21(8):1869.
[18]Ahlberg A, Eriksson O, Kjellman H. Diffusion of tranexamic acid to the joint. Acta Orthopaedica. 1976;47(5): 486-488.
[19]Nilsson IM. Clinical pharmacology of aminocaproic and tranexamic acids. J Clin Pathol. 1980;33(Suppl 14):41-47.
[20]Benoni G, Lethagen S, Nilsson P, et al. Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty. Acta Orthop Scand. 2000;71:250-254.
[21]Good L, Peterson E, Lisander B. Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Br J Anaesth. 2003;90(5):596.
[22]Lin PC, Hsu CH, Chen WS, et al. Does tranexamic acid save blood in minimally invasive total knee arthroplasty? Clin Orthop Relat Res. 2011;469(7):1995.
[23]余世明,刘建华,徐栋梁,等.兔用生物型人工膝关节假体的设计与制作[J].中华关节外科杂志(电子版), 2009,3(4):63-66.
[24]Bao N, Zhou L, Cong Y, et al. Free fatty acids are responsible for the hidden blood loss in total hip and knee arthroplasty. Med Hypoth. 2013;133(1)104-107.
[25]McManus KT, Velchik MG, Alavi A, et al. Non-invasive assessment of postoperative bleeding in TKA patients with Tc-99m RNCs. J Nuclear Med. 1987;28(8): 565-567.
[26]Zampelis V, Tägil M, Lidgren L, et al. The effect of a biphasic injectable bone substitute on the interface strength in a rabbit knee prosthesis model. J Orthop Surg Res. 2013; 8(1): 25.
[27]Mauerer A, Lange B, Welsch GH, et al. Release of Cu2+ from a copper-filled TiO2 coating in a rabbit model for total knee arthroplasty. J Mat Sci. 2014;25(3):813-821.
[28]余世明,刘建华,徐栋梁,等.兔用生物型人工膝关节假体的设计与制作[J].中华关节外科杂志(电子版), 2009,3(4):63-66.
[29]严志强,张乐,王新亮,等.计算机辅助设计兔解剖型人工膝关节假体[J].广东医学,2014,35(13):1997-2001.
[30]严俊伟,唐成,李祥全,等.全膝关节置换术后感染模型的建立[J]. 中华关节外科杂志(电子版),2014,8(1):60-64.
[31]高福强,李子剑,刘延青,等.初次全膝关节置换术后肢体肿胀程度与隐性失血量的相关性研究[J].中国矫形外科杂志,2011,19(3): 199-202.
[32]Randelli F, D’Anchise R, Ragone V, et al. Is the newest fibrin sealant an effective strategy to reduce blood loss after total knee arthroplasty? A randomized controlled study. J Arthroplasty. 2014;29(8):1516-1520.
[33]Alshryda S,Mason J,Vaghela M,et al.Topical(intra-articular) tranexamic acid reduces blod los and transfusion rates folowingtotal kne replacement:a randomized controled trial(TRANX-K).J Bone Joint Surg Am. 2013;95 (21):1961-1968.
[34]Wind TC, Barfield WR, Moskal JT. The effect of tranexamic acid on transfusion rate in primary total hip arthroplasty. J Arthroplasty. 2014; 29(2):387-389.
[35]甘伟伟,刘斌,谢贵杰.氨甲环酸应用时机对髋关节置换手术患者失血量影响的研究[J].安徽医药, 2014,18(8):1569-1571.
[36]Alcelik I, Pollock RD, Sukeik M, et al. A comparison of outcomes with and without a tourniquet in total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials. J Arthroplasty. 2012;27(3): 331-340.
[37]Zan PF, Yang Y, Fu D, et al. Releasing of tourniquet before wound closure or not in total knee arthroplasty: a meta-analysis of randomized controlled trials. J Arthroplasty. 2015;30(1):31-37.
[38]陈虎,曹力,杨德盛,等.麻醉方式与全膝关节置换术后深静脉血栓发生率分析[J].中国矫形外科杂志, 2012, 20(5): 402-405.
[39]Jiang X, Hand AR, Shen S, et al. Enhanced tissue plasminogen activator synthesis by the sympathetic neurons that innervate aging vessels. J Neurosci Res. 2003;71(4): 567-574.
[40]Bell TH, Berta D, Ralley F, et al. Factors affecting perioperative blood loss and transfusion rates in primary total joint arthroplasty: a prospective analysis of 1642 patients. Can J Surg. 2009;52(4): 295.
[41]Mega JL, Braunwald E, Wiviott SD. Low doses of rivaroxaban effectively lower the risk of cardiac events. Am J Cardiol. 2013.
[42]Tai TW,Chang CW,Yang CY,et al. Effects of tourniquet use on blood loss and soft-tissue damage in total knee arthroplasty: a randomized controlled trial. J Bone Joint Surg Am. 2012; 94(24): 2209-2215.
[43]Kumar GS, Von Arx OA, Pozo JL. Rate of blood loss over 48 hours following total knee replacement. Knee. 2005;12(4): 307-309.