Administration of tranexamic acid in primary total joint arthroplasty

Rafal Kaminski＊

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

INTRODUCTION

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

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 modi fications in surgical techniques, but the greatest advancement in lowering perioperative blood loss after total knee arthroplasty (TKA)or total hip arthroplasty (THA) has been the introduction of TXA

One signi ficant concern with TXA is the possibility that it could increase the risk of developing thromboembolic complications such as deep vein thrombosis. Most of the metaanalyses 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 anti fibrinolytic drugs, such as aprotinin, epsilon aminocaproic acid and fibrin spray,have been tested for ef ficacy in decreasing surgical blood loss and improving transfusion rate (Kagoma et al., 2009).All analyses showed lower ef ficacy (epsilon aminocaproic acid) or more side effects (aprotinin) than TXA. Interestingly, all other anti fibrinolytics were not as cost effective as TXA (McGoldrick, 2015). The cost bene fit analyses performed so far in case of TKA or THA showed bene fit 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 Anti fibrinolytic in Signi ficant 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 signi ficantly 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 signi ficantly 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 signi ficant difference was noticed in case of deep venous thrombosis when used in patients compared with rivaroxaban or dabigatran.

CONCLUSIONS

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 signi ficant financial savings. Still, some uncertainties exist. More studies are encouraged to optimize the dosing and route of administration.

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