The most important finding of the present study was that usage of TXA can decrease not only the perioperative blood loss, transfusion rate and supplemental amount of FVIII but also swelling ratio and surgical joint pain. Moreover, compared with non-TXA group, the patients in TXA group had a lower level of inflammatory biomarkers and better joint function.

The perioperative blood loss in primary TJA includes overt blood loss, composed of intraoperative blood loss and postoperative drainage, and hidden blood loss, such as extravasation into the tissue, residual blood in the joint, and loss due to hemolysis, accounts for even 50% of the total blood loss [19]. According to our previous comparable studies available in non-haemophilic patients [9,10,11, 14], using combination of intravenous and topical application of TXA could gain less total blood loss, less intraoperative blood loss, maximum Hb decline and less drainage. In the current study, we found similar benefits of using TXA in haemophilic patients. What is more, we also found that using TXA could significantly reduce the total amount of FVIII factors during the perioperative period. This extra finding was also suggested by studies [20,21,22] focusing on the TXA as adjunct therapy to daily treatment of haemophilia A patients with inhibitors. The possible mechanism is that TXA can stabilize clot, improving haemostatic effect in patients with haemophilia.

In the current study, we also found that patients using TXA tend to have a significant lower level of inflammatory biomarkers, such as CRP and IL-6. There are several possible reasons underlying the anti-inflammatory effects observed in TXA group. Firstly, previous studies showed that TXA could attenuate inflammatory responses through blockade of fibrinolysis [23,24,25]. Secondly and most importantly, TXA reduced total blood loss, translating into reduced total surgical trauma [17] since postoperative blood loss and pain were shown to positively synergize with postoperative inflammation and surgical trauma as demonstrated by CRP, IL-6 and IL-1 levels [17, 26], which might also explain why there was a lower joint swelling ratio observed in the TXA group during the postoperative days. Holem et al. [27] have demonstrated that joint swelling after TJA is mainly due to intra-articular bleeding and inflammation of the periarticular tissues. Since TXA can decrease not only blood loss but also local inflammation [14, 28, 29], it would not be surprising to find that patients in TXA group had a significantly lower swelling ratio compared to those from non-TXA group.

In most patients with haemophilia, arthrofibrosis accompanies the joint destruction seen with the recurrent bleeding episodes within the joint [8, 13]. Patients often have significantly limited ROM of the joints. In our study, a significant increase in ROM and a reduction of the pain after TJA in haemophilic patients was observed in both groups. Furthermore, substantial improvements of joint function as determined by either KSS or HHS were demonstrated. The results were comparable with the follow-up results of haemophilic patients undergoing TJA reported by previous studies [30, 31]. In addition, we observed that patients in the TXA groups would have better clinical outcomes at in the early follow-up time points both measured by ROM and functional scales. There might be several reasons for this. For one thing, swelling and intra-articular bleeding have been reported to associate with decreased ROM and function especially in patients with bleeding disorders [13]. Because of using TXA, swelling and intra-articular bleeding were significantly decreased, thus the patients would have a better ROM and function. For another, patients in TXA group had less pain in their operated joints. With better pain control in those patients, they would be more likely to involve into the early rehabilitation. It has been previously reported that although ROM is significantly improved in patients with haemophilia, a substantial number of patients will require manipulation under anesthesia and even lysis of adhesions to gain or maintain a functional ROM [8, 32, 33]. However, we did not observe re-stiffness in our patients. That might be attributed to our emphasis on the early-reached required ROM in the rehabilitation program, that is to encourage patients to reach their maximum ROM during the first 48 h postoperatively before the contracture of the fibrous tissue around the surgical site and the previous rehabilitation is to maintain the maximum ROM.

Previous literatures have reported patients receiving TJA because of haemophilia had significant higher infection rates ranging from 8 to 16% [6, 8, 34]. In our study, no periprosthetic joint infection was found at the last follow-up time points, which we believe mainly lies in the relatively short follow-up. With a special emphasis on late PJI, Rodriguez-Merchan et al. reported an infection rate of 2.8% at early follow-up [34] and then a rate of 6.8% at a later follow-up [3]. Some other groups even reported that four of five knees with PJI had late infection, and the average time for revision was 12 ± 4 years. Thus, we have emphasized the possibility of PJI in these patients and asked them to do the follow-up at least once every year.

The main concern of using TXA in patients undergoing TJA is the possibility of increasing the risk of DVT and PE postoperatively. However, it has been previously reported that DVT rate in patients with haemophilia was considered very low due to impaired coagulation activity. Herman et al. [35] reported that among 29 orthopaedic surgeries in 22 patients without using pharmacological thrombo-prophylaxis, only three subclinical DVTs were detected by Doppler ultrasound. In our study, we did not use pharmacological thrombo-prophylaxis in either groups. We performed Doppler ultrasound at POD5, the time of discharge, 1, 3 and 6-month follow-up. No DVT events were reported in both groups. This finding was consistent with the outcome reported by previous studies that the rate of DVT was much lower than that in non-haemophilia patients. None of the patients required CT to rule out PE.

There are limitations to our study. First and foremost, it is the retrospective design nature. We included the patients with enough follow-up information and otherwise excluded to avoid potential selection. Secondly, we did not calculate the needed sample size before the study. A larger sample size might be needed to detect significance in assessment outcomes between the groups. Third longer follow-up was needed to assess the long-term effects of TXA. The strength of our study that all procedures were performed by a single team of surgeons at a single academic institution using modern perioperative management protocols.