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 Table of Contents  
CORRESPONDENCE
Year : 2016  |  Volume : 1  |  Issue : 3  |  Page : 118-120

Administration of tranexamic acid in primary total joint arthroplasty


Department of Traumatology and Orthopaedics, Center for Postgraduate Medical Education, A. Gruca Hospital, Otwock, Poland

Date of Web Publication31-Aug-2016

Correspondence Address:
Rafal Kaminski
Department of Traumatology and Orthopaedics, Center for Postgraduate Medical Education, A. Gruca Hospital, Otwock
Poland
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2468-5674.189513

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  Abstract 

One of the concerning problems with total joint arthroplasties is a need for postoperative blood transfusion. Currently, evidence is gathered that allogenic blood transfusion has more disadvantages than previously thought. It is an independent risk factor that boosts infection rate, it increases total cost of joint arthroplasty and amplifies the risk of fluid overload as well as increases length of hospital stay. In the search for factors that may contribute to influencing the need for blood transfusion, tranexamic acid has been tested. Currently, it has a well-documented effect on reduction of intra- and postoperative blood loss and transfusion requirements in patients undergoing total knee arthroplasty. In this brief review, we will discuss documented use of tranexamic acid in total joint arthroplasties, focusing on the hip joint.

Keywords: tranexamic acid; tranexamic acid; blood loss; total joint arthroplasty; total hip arthroplasty


How to cite this article:
Kaminski R. Administration of tranexamic acid in primary total joint arthroplasty. Clin Trials Orthop Disord 2016;1:118-20

How to cite this URL:
Kaminski R. Administration of tranexamic acid in primary total joint arthroplasty. Clin Trials Orthop Disord [serial online] 2016 [cited 2019 Jul 23];1:118-20. Available from: http://www.clinicalto.com/text.asp?2016/1/3/118/189513


  Introduction Top


The fibrinolytic inhibitor tranexamic acid (TXA) was developed in the 1960s and was used in clinical setting to prevent excessive blood loss (Tengborn et al., 2015). It reversibly blocks receptor sites on plasminogen and plasmin, thus preventing plasmin from degrading fibrin. It is estimated that it is eight times more potent than ε-aminocaproic acid (previously used medication). It is widely used to block fibrinolysis during major trauma, heavy menstrual bleeding, and different surgery types: trauma, neuro-, cardiac-, orthopedic, gynecological, oral and many more. It could be administered intravenously, intramuscularly, orally or via topical route. The adverse reactions are usually mild and occur ≤ 5% more frequently than placebo (Hurskainen and Leminen, 2012). Still, the issue whether TXA is thrombogenic is widely discussed (Ross and Al-Shahi Salman, 2012)., So far, no increase in thrombotic events (deep veonous thrombosis or embolism) has been proven (Xu et al., 2015; Yue et al., 2015; Rodriguez-Merchan et al., 2016).


  Orthopaedic surgery Top


Surgery for total joint arthroplasties is common with a reported transfusion rate of approximately 26.8% (Stokes et al., 2011). Perioperative blood management programmes are introduced to reduce the rate of blood transfusion. The improvements so far are made by modifications in surgical techniques, but the greatest advancement in lowering peri-operative blood loss after total knee arthroplasty (TKA) or total hip arthroplasty (THA) has been the introduction of TXA

One significant concern with TXA is the possibility that it could increase the risk of developing thromboembolic complications such as deep vein thrombosis. Most of the meta-analyses show no or minimal differences in the incidence of thromboembolic complications with the use of TXA, so it is worth emphasizing that it reduces blood loss without increasing the risk of thromboembolic events (Gandhi et al., 2013). In other trials, other antifibrinolytic drugs, such as aprotinin, epsilon aminocaproic acid and fibrin spray, have been tested for efficacy in decreasing surgical blood loss and improving transfusion rate (Kagoma et al., 2009). All analyses showed lower efficacy (epsilon aminocaproic acid) or more side effects (aprotinin) than TXA. Interestingly, all other antifibrinolytics were not as cost effective as TXA (McGoldrick, 2015). The cost benefit analyses performed so far in case of TKA or THA showed benefit rounding up to 900 GBP (Benoni et al., 2001; Good et al., 2003; Ralley et al., 2010).

Existing problem is dosing of TXA. The intravenous route was extensively evaluated, especially in trauma (CRASH-2 trial - Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) or with profuse postpartum hemorrhage (Williams-Johnson et al., 2010; Ducloy-Bouthors et al., 2011). Several high quality clinical trials evaluating the effect of TXA in reducing blood loss and transfusion requirements in primary THA or TKA have been published in recent years, but the optimal doses and protocols have not been established, yet.

Usually, TXA is given through intravenous route, although intra-operative topical route is being showing up. Intravenous protocol consists of TXA given intravenously in a dose of 10-15 mg/kg (or 1 g) immediately before surgery followed or not by repeated dose after 3 hous. Usually with this regimen the concentration of TXA is ≥ 10 mg/L (considered to be therapeutic (Andersson et al., 1968). Detailed analysis of the trials showed that the frequency of patients who required transfusion is usually higher than that of patients treated with single-dose regimen. It might suggest that the single-dose cannot fully cover the bleeding period. All these results seem to support a two-dose TXA.

Topical administration during TKA or THA has been proposed. Different techniques are used in the studies: 1) wound irrigation, and 2) intra-articular administration through drainage with clamping. Although there is no optimal protocol described, it has been shown to significantly reduce total blood loss in the groups receiving TXA. Still no optimal dose has been described. Studies vary from 0.5 g in saline for 2-5 minutes postoperatively to high-concentration solutions with 20 mg/mL or more TXA. In the meta-analyses the subgroup analysis showed that high-concentration TXA may be better at reducing bleeding and transfusions than low-concentration TXA without significantly increasing the risk of deep venous thrombosis and pulmonary embolism (Xu et al., 2015; Yue et al., 2015; Rodriguez-Merchan et al., 2016). Similarly, same observations were made in case of upper limb arthroplasties (shoulder) (Gillespie et al., 2015).

The question arises how to use TXA in the new oral anticoagulant drugs era. There are inconsistent data from in vitro and in vivo experiments. So far there is only one clinical trial reporting this issue (Zhirova et al., 2014). In this (limited) study no significant difference was noticed in case of deep venous thrombosis when used in patients compared with rivaroxaban or dabigatran.[18]


  Conclusion Top


Introduction of TXA in lower and upper limb arthroplasty greatly reduces blood loss. This leads to lower transfusion rates, lower number of complications, shorter in-hospital stay and significant financial savings. Still, some uncertainties exist. More studies are encouraged to optimize the dosing and route of administration.

 
  References Top

1.
Andersson L, Nilsoon IM, Colleen S, Granstrand B, Melander B (1968) Role of urokinase and tissue activator in sustaining bleeding and the management thereof with EACA and AMCA. Ann N Y Acad Sci 146:642-658.  Back to cited text no. 1
    
2.
Benoni G, Fredin H, Knebel R, Nilsson P (2001). Blood conservation with tranexamic acid in total hip arthroplasty: a randomized, double-blind study in 40 primary operations. Acta Orthop Scand 72:442-448.  Back to cited text no. 2
    
3.
Ducloy-Bouthors AS, Jude B, Duhamel A, Broisin F, Huissoud C, Keita-Meyer H, Mandelbrot L, Tillouche N, Fontaine S, Le Goueff F, Depret-Mosser S, Vallet B; EXADELI Study Group, Susen S (2011) High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care 15:R117.  Back to cited text no. 3
    
4.
Gandhi R, Evans HM, Mahomed SR, Mahomed NN (2013) Tranexamic acid and the reduction of blood loss in total knee and hip arthroplasty: a meta-analysis. BMC Res Notes 6:184.  Back to cited text no. 4
    
5.
Gillespie R, Shishani Y, Joseph S, Streit JJ, Gobezie R (2015) Neer Award 2015: A randomized, prospective evaluation on the effectiveness of tranexamic acid in reducing blood loss after total shoulder arthroplasty. J Shoulder Elbow Surg 24:1679-1684.  Back to cited text no. 5
    
6.
Good L, Peterson E, Lisander B (2003) Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Br J Anaesth 90:596-599.  Back to cited text no. 6
    
7.
Leminen H, Hurskainen R (2012) Tranexamic acid for the treatment of heavy menstrual bleeding: efficacy and safety. Int J Womens Health 413-421.  Back to cited text no. 7
    
8.
Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W (2009) Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res 123:687-696.  Back to cited text no. 8
    
9.
McGoldrick NP (2015) Cost benefit analysis of the use of tranexamic acid in primary lower limb arthroplasty: a retrospective cohort study. World J Orthop 6:977.  Back to cited text no. 9
    
10.
Ralley FE, Berta D, Binns V, Howard J, Naudie DD (2010) One intraoperative dose of tranexamic acid for patients having primary hip or knee arthroplasty. Clin Orthop 468:1905-1911.  Back to cited text no. 10
    
11.
Rodriguez-Merchan EC, Ortega-Andreu M, Padilla-Eguiluz NG, Gomez-Cardero P, Martinez-Lloreda Á, Gomez-Barrena E (2016) Low-volume formulation of intra-articular tranexamic acid, 25-ml tranexamic acid (2.5  g) plus 20-ml saline, is effective in decreasing blood transfusion rate in primary total knee replacement even without preoperative haemoglobin optimization. Blood Coagul Fibrinolysis doi: 10.1097/MBC.0000000000000457.  Back to cited text no. 11
    
12.
Ross J, Al-Shahi Salman R (2012) The frequency of thrombotic events among adults given antifibrinolytic drugs for spontaneous bleeding: systematic review and meta-analysis of observational studies and randomized trials. Curr Drug Saf 7:44-54.  Back to cited text no. 12
    
13.
Stokes ME, Ye X, Shah M, Mercaldi K, Reynolds MW, Rupnow MF, Hammond J (2011) Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients. BMC Health Serv Res 11:135.  Back to cited text no. 13
    
14.
Tengborn L, Blombäck M, Berntorp E (2015) Tranexamic acid - an old drug still going strong and making a revival. Thromb Res 135:231-242.  Back to cited text no. 14
    
15.
Williams-Johnson JA, McDonald AH, Strachan GG, Williams EW (2010) Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2) A randomised, placebo-controlled trial. West Indian Med J 59:612-624.  Back to cited text no. 15
    
16.
Xu X, Xiong S, Wang Z, Li X, Liu W (2015) Topical administration of tranexamic acid in total hip arthroplasty: a meta-analysis of randomized controlled trials. Drug Discov Ther 9:173-177.  Back to cited text no. 16
    
17.
Yue C, Pei F, Yang P, Xie J, Kang P (2015) Effect of topical tranexamic acid in reducing bleeding and transfusions in TKA. Orthopedics 38:315-324.  Back to cited text no. 17
    
18.
Zhirova TA, Lykov MS, Zyrianov MN, Babushkin VN (2014) New oral anticoagulants for thromboprophylaxis under routine use of tranexamic acid after hip joint arthroplasty. Anesteziol Reanimatol 59:34-38.  Back to cited text no. 18
    




 

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