Oral Tranexamic Acid in Hip and Knee Arthroplasty: A Prospective Cohort Study

Abstract

Intravenous Tranexamic acid has been shown to decrease blood transfusion requirements in sur- gery. Little evidence exists regarding the much cheaper oral form. The objective of this cohort study was to evaluate whether oral tranexamic acid administration in patients undergoing elec- tive hip and knee replacement surgery resulted in decreased transfusion requirements. Methods: We assessed the transfusion requirements of 332 patients following unilateral total hip or knee arthroplasty, with the first 140 receiving no tranexamic acid and the next 192 given 1 g oral tranexamic acid one hour prior to and a further 1 g 4 hours post joint arthroplasty. Haemoglobin before and after surgery, the number of units transfused post-operatively and the incidence of deep vein thrombosis or pulmonary embolism were recorded. Results: In the first group, there were 22 instances of transfusion (15.7%) and a mean haemoglobin drop of 32.2 g/L, while the second (tranexamic acid) group had just 12 patients transfused (6.3%) and a mean haemoglobin drop of 24.6 g/L (both significantly less, p < 0.01). There was no significant difference in deep vein thrombosis or pulmonary embolism rates between groups. Conclusions: This is the first prospective study to analyze the outcome of oral tranexamic acid administration in hip and knee replacement. We conclude that oral tranexamic acid administration is a safe and effective means to decrease transfusion requirements in joint arthroplasty and is a much cheaper alternative to intravenous preparations of tranexamic acid.

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McGrath, S. , Yates, P. and Prosser, G. (2014) Oral Tranexamic Acid in Hip and Knee Arthroplasty: A Prospective Cohort Study. Open Journal of Orthopedics, 4, 215-220. doi: 10.4236/ojo.2014.48035.

Pulmonary Embolus (PE), or any other complications at the 3-month outpatient clinic follow-up.

2.3. Statistical Analysis

An unpaired t-test comparison was made to analyze the haemoglobin drop between groups. A chi-squared test was utilized to compare the rates of transfusion as well as instances of DVT and PE.

3. Results

3.1. Transfusion Requirements

The mean Hb drop for the pre-TXA control group was 32.2 g/L and significantly less (p < 0.0001) for the TXA group at 24.6 g/L. The number of patients transfused was lower in the TXA group (12 patients, 6.3%) versus the control group (22 patients, 15.7%) as seen in Table2 This difference was significant (p = 0.005). Out of the 22 and 12 patients transfused for the control and TXA groups respectively, 41 units were transfused to the control group and 20 to the TXA group.

3.2. Follow-Up & Complications

The mean follow-up was 133 days. In the TXA group, there was one documented non-ST elevation Myocardial Infarction (NSTEMI), one DVT and three instances of PE confirmed by Computed Tomography Pulmonary Angiogram (CTPA). None of the transfused patients had been on anticoagulant medication prior to transfusion. In the control group, there was one incidence of DVT recorded. There was not a significant difference between groups in DVT or PE rates (p 0.822 and 0.137 respectively) as represented in Table3 It should also be noted that eight of the 192 patients in the TXA group had previously had either a DVT or PE documented in their past medical history and none of the eight suffered a further DVT/PE in this study. Three patients went on to require further surgery for peri-prosthetic fractures after a fall or dislocation, 2 patients required washout for infection, 3 had manipulation for stiffness and there were 2 instances of wound cellulitis.

4. Discussion

The results of our study suggest that administration of oral tranexamic acid before and after joint replacement surgery is effective in decreasing haemoglobin drop, and blood transfusion rates with no significant increase in thrombotic complications. This is the first prospective study to analyze the outcome of oral tranexamic acid administration in hip and knee replacement.

High quality data including a Cochrane review [4] and meta-analysis [14] have confirmed the general efficacy

Table 2 . Post-operative results. 

*p-value statistically significant.

Table 3. Thromboembolic complications. 

of IV TXA in reducing ABT in surgery. Within the orthopaedic literature a meta-analysis looking at TXA in total hip arthroplasty confirmed the same with no difference in DVT/PE or complication rates but notably excluded oral TXA usage [6] . Similarly another systematic review of 19 randomized controlled trials of TXA in total knee replacement (TKR) showed reduced blood loss, transfusion rate and no increase in complications [15] . This review did include one oral TXA study by Zohar et al. [16] from 2004 involving 80 TKR patients divided into four groups of 20 patients. The three treatment groups were either given IV TXA, oral TXA or a combination both preand post-operatively. The rates of transfusion were significantly higher in the control group compared with the treatment arms and no significant difference was observed between the three TXA groups. The authors therefore concluded that despite different doses between groups, oral TXA by virtue of its simplicity in administration was more advantageous. A recently published, large retrospective analysis of 3000 joint replacement patients in the United Kingdom looked back at the outcomes of oral TXA administration over two short time periods in which a national shortage limited the IV supply [17] . They concluded that oral TXA (25 mg/kg to a maximum of 2 g given 2 hours prior) showed a similar safety profile to IV (15 mg/kg to a maximum of 1.2 g given at induction), and found, significantly, the odds ratio for receiving a transfusion higher in the IV group (n = 2698) than the oral (n = 302).

Many studies [11] -[13] have looked at the timing of TXA administration in the intravenous form with little or no difference between groups other than the difference seen between treatment and control (with no TXA given). Our simple regimen was to give 1 g 1 hour prior and a further 1 g 4 hours post-replacement surgery. We found no significant difference in rates of symptomatic venous thromboembolism than expected with one DVT and 3 instances of PE in the TXA group and one instance of DVT in the control group. This reflects previous studies that found no increase in thromboembolic complications with TXA use [17] -[20] .

In May 2010, the World Health Organisation adopted the three pillars of patient blood management (PBM) [21] . The second pillar of patient blood management concerns strategies to minimize blood loss. Prior to this study in Western Australia, orthopaedic surgery accounted for 17% of all transfusions (2008 to 2009) [22] , with cost estimated at around $875 per transfused unit in 2010 [23] . Our findings demonstrated a significant decrease in haemoglobin drop with oral tranexamic acid therapy and this led to a decreased rate of transfusion. Certainly this has direct implications in not only blood product conservation but also cost-saving from decreased blood product utilization and the relatively cheaper cost of oral tranexamic acid administration. At our institution a 1 g intravenous preparation of tranexamic acid cost $60.17, whereas the equivalent oral dose cost only 0.82 cents ($40.76 for 100 × 500 mg tablets), representing an over 70-fold saving with oral TXA. The present study therefore highlights one simple and effective means of decreasing the demand and cost burden of transfusion, whilst complying with international recommendations.

Limitations

Western Australia has been at the forefront of PBM and has implemented a health-system-wide program since 2008 [21] . The current study involves just one component of the PBM system, however it also occurs at a time where the context is rapidly changing and the results have to be interpreted in the light of this. This study is not a randomized controlled trial where the subjects can be isolated from other good strategies that are occurring at a State-wide level. One such example relates to the first pillar of PBM which aims to optimize red cell mass; all patients presenting for elective joint replacement within the present institution will be screened for anaemia and pre-operatively optimized with treatment of underlying disorders like iron deficiency. One strategy therefore to improve our study would be to conduct a large randomized controlled trial comparing oral and IV TXA administration and attempt to measure all other variables within the PBM context such as concomitant iron administration and anticoagulation.

5. Conclusion

Our data suggest that oral TXA administration in the context of a PBM program decreases transfusion requirement without increased complications. This has implications for clinical practice, as oral TXA is simpler and significantly cheaper to administer.

Conflicts of Interest

The authors declare no conflicts of interest.

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