According to the retrieval strategy, 232 articles were initially obtained, of which 96 were excluded according to the type of articles by title evaluation. Through reviewing the abstract and full text, 136 studies (396 comparisons) [7-142] were finally included to compare the efficacy of TXA in reduction of TBL, transfusion rate, Hb drop, mortality, DVT and PE as shown in Figure 1. The effect sizes of each meta-analysis and baseline characteristics for 136 meta-analyses of TXA related to TKA, THA, postpartum bleeding, intertrochanteric fractures, orthopaedic surgery, spinal surgery, shoulder arthroplasty, hip fracture surgery, menstrual bleeding, plastic surgery, cardiac surgery, nasal surgery, gastrointestinal bleeding, trauma, liver surgery, cancer and myomectomy reported were shown in Table 2.
According to the largest studies, the meta-analyses of TXA using for TKA, THA, postpartum bleeding, intertrochanteric fractures, orthopaedic surgery, spinal surgery, shoulder arthroplasty, hip fracture surgery, menstrual bleeding, plastic surgery and nasal surgery reported significantly reduced TBL; the meta-analyses of TXA using for liver surgery and myomectomyreported reported that there was no significant difference in TBL; the meta-analyses of TXA using for cardiac surgery reported significantly increased TBL. The meta-analyses of TXA using for TKA, THA, postpartum bleeding, intertrochanteric fractures, orthopaedic surgery, shoulder arthroplasty, hip fracture surgery reported significantly reduced Hb drop; the meta-analyses of TXA using for TKA, THA, postpartum bleeding, intertrochanteric fractures, liver surgery, orthopaedic surgery, spinal surgery, hip fracture surgery, cancer and cardiac surgery reported significantly reduced transfusion rate; the meta-analyses of TXA using for trauma, shoulder arthroplasty, gastrointestinal bleeding, plastic surgery and myomectomy reported there was no significant difference in transfusion rate. The meta-analyses of TXA using for TKA, THA, postpartum bleeding, intertrochanteric fractures, orthopaedic surgery, spinal surgery, shoulder arthroplasty, liver surgery, trauma, gastrointestinal bleeding and cardiac surgery reported there was no significant difference in DVT. The meta-analyses of TXA using for TKA, THA, trauma, intertrochanteric fractures and cardiac surgery reported there was no significant difference in PE. The meta-analyses of TXA using for trauma and gastrointestinal bleeding reported significantly reduced mortality; the meta-analyses of TXA using for liver surgery and cardiac surgery reported there was no significant difference in mortality as shown in Table 3.
However, considering all the effect sizes of the included studies, the results were controversial. Among them, 25 of 26 comparisons about TKA, 2 of 3 comparisons about TKA/THA, 8 of 10 comparisons about postpartum bleeding, 2 of 3 comparisons about cardiac surgery and all comparisons about THA, intertrochanteric fractures, orthopaedic surgery, spinal surgery, shoulder arthroplasty, hip fracture surgery, menstrual bleeding, plastic surgery, myomectomy and nasal surgery still suggested a significant reduction of TBL. 1 of 26 comparisons about TKA, 1 of 3 comparisons about TKA/THA, 2 of 10 comparisons about postpartum bleeding and all comparisons about liver surgery suggested no significant difference on TBL. 1 of 3 comparisons about cardiac surgery suggested a significant increase on TBL compared with aprotinin. 6 comparisons evaluated the effect of intravenous combined topical application of TXA on TBL in TKA compared with intravenous or topical application of TXA alone. The results of 6 comparisons showed that the combined use of TXA significantly reduced TBL compared with TXA alone; 9 comparisons evaluated the effect of intravenous, topical or oral TXA on TBL in TKA. The results of 1 comparison showed that intravenous use of TXA significantly increased TBL compared with topical application of TXA; 8 comparisons showed that there was no significant difference among the three types of administration for TBL. 4 comparisons evaluated the effect of intravenous combined topical application of TXA on TBL in THA compared with intravenous or topical application of TXA alone. The results of 4 comparisons showed that the combined use of TXA significantly reduced TBL compared with TXA alone; 5 comparisons evaluated the effect of intravenous, topical or oral TXA on TBL in THA. The results of 5 comparison showed that there was no significant difference among the three types of administration for TBL. 4 comparisons evaluated the effect of intravenous combined topical application of TXA on TBL in TKA/THA compared with intravenous or topical application of TXA alone. The results of 4 comparisons showed that the combined use of TXA significantly reduced TBL compared with TXA alone; 5 comparisons evaluated the effect of intravenous, topical or oral TXA on TBL in TKA/THA. The results of 5 comparison showed that there was no significant difference among the three types of administration for TBL.
15 of 16 comparisons about THA, 2 of 3 comparisons about TKA/THA, 8 of 9 comparisons about postpartum bleeding, 7 of 12 comparisons about spinal surgery,3 of 4 comparisons about shoulder arthroplasty, 9 of 11 comparisons about cardiac surgery and all comparisons about TKA, intertrochanteric fractures, liver surgery, orthopaedic surgery, hip fracture surgery and cancer still suggested a significant reduction of transfusion rate; 1 of 16 comparisons about THA, 1 of 3 comparisons about TKA/THA, 1 of 9 comparisons about postpartum bleeding, 5 of 12 comparisons about spinal surgery, 1 of 4 comparisons about shoulder arthroplasty, 2 of 11 comparisons about cardiac surgery and all comparisons about trauma, gastrointestinal bleeding, plastic surgery and myomectomy suggested no significant difference on transfusion rate. 6 comparisons evaluated the effect of intravenous combined topical application of TXA on transfusion rate in TKA compared with intravenous or topical application of TXA alone. The results of 1 comparison showed that the combined use of TXA significantly reduced transfusion rate compared with TXA alone in TKA; 5 comparisons showed that there was no significant difference between the combined and separate administration in TKA. 8 comparisons evaluated the effect of intravenous, topical or oral TXA on transfusion rate in TKA. All comparisons showed that there was no significant difference among the three types of administration for transfusion rate. 2 comparisons evaluated the effect of intravenous combined topical application of TXA on transfusion rate in THA compared with intravenous or topical application of TXA alone. The results of 2 comparisons showed that the combined use of TXA significantly reduced transfusion rate compared with TXA alone. 3 comparisons evaluated the effect of intravenous, topical or oral TXA on transfusion rate in THA. The results of 3 comparison showed that there was no significant difference among the three types of administration for transfusion rate. 2 comparisons evaluated the effect of intravenous combined topical application of TXA on transfusion rate in TKA/THA compared with intravenous or topical application of TXA alone. The results of 2 comparisons showed that the combined use of TXA significantly reduced transfusion rate compared with TXA alone. 5 comparisons evaluated the effect of intravenous, topical or oral TXA on transfusion rate in TKA/THA. The results of 5 comparisons showed that there was no significant difference among the three types of administration for transfusion rate.
3 of 4 comparisons about shoulder arthroplasty and all comparisons about TKA, THA, TKA/THA, postpartum bleeding intertrochanteric fractures, orthopaedic surgery and hip fracture surgery still suggested a significant reduction of Hb drop; 1 of 4 comparisons about shoulder arthroplasty suggested no significant difference on Hb drop. 2 comparisons evaluated the effect of intravenous combined topical application of TXA on Hb drop in TKA compared with intravenous or topical application of TXA alone. The results of 2 comparisons showed that the combined use of TXA significantly reduced Hb drop compared with TXA alone in TKA. 7 comparisons evaluated the effect of intravenous and topical TXA on Hb drop in TKA. The results of 1 comparison showed that the intravenous use of TXA significantly reduced Hb drop compared with topical application of TXA in TKA; 6 comparisons showed that there was no significant difference between the two types of administration for Hb drop. 4 comparisons evaluated the effect of intravenous combined topical application of TXA on Hb drop in THA compared with intravenous or topical application of TXA alone. The results of 3 comparisons showed that the combined use of TXA significantly reduced Hb drop compared with TXA alone in THA; 1 comparison showed that there was no significant difference. 3 comparisons evaluated the effect of intravenous and topical TXA on Hb drop in THA. The results of 1 comparison showed that the intravenous use of TXA significantly reduced Hb drop compared with topical application of TXA in THA; 2 comparisons showed that there was no significant difference between the two types of administration for Hb drop. 3 comparisons evaluated the effect of intravenous combined topical application of TXA on Hb drop in TKA/THA compared with intravenous or topical application of TXA alone. The results of 3 comparisons showed that the combined use of TXA significantly reduced Hb drop compared with TXA alone. 6 comparisons evaluated the effect of intravenous, topical or oral TXA on Hb drop in TKA/THA. The results of 2 comparisons showed that intravenous use of TXA significantly reduced Hb drop compared with oral or topical application of TXA; 4 comparison showed that there was no significant difference among the three types of administration for Hb drop.
2 of 3 comparisons about trauma, 2 of 7 comparisons about cardiac surgery and all comparisons about gastrointestinal bleeding still suggested a significant reduction of mortality; 1 of 3 comparisons about trauma, 5 of 7 comparisons about cardiac surgery and all comparisons about liver surgery suggested no significant difference on mortality.
All comparisons about TKA, THA, TKA/THA, postpartum bleeding, intertrochanteric fractures, orthopaedic surgery, spinal surgery, shoulder arthroplasty, liver surgery, trauma, gastrointestinal bleeding, cardiac surgery showed that there was no significant difference on DVT.
All comparisons about TKA, THA, trauma, intertrochanteric fractures, cardiac surgery showed that there was no significant difference on PE.
A summary of evidence from the retrieved meta-analyses of TXA is shown in Table 4. The evidence for TXA using in TKA (combine administration vs single administration; TXA vs placebo), THA (combine administration vs single administration; TXA vs placebo), TKA/THA (combine administration vs single administration; TXA vs placebo), postpartum bleeding, intertrochanteric fractures, orthopaedic surgery, spinal surgery, shoulder arthroplasty, hip fracture surgery, cardiac surgery, menstrual bleeding, plastic surgery, myomectomy, nasal surgery was assessed as possible for the association of reducing TBL. There was probably no association between TXA and TBL in TKA (IV TXA vs topical/oral TXA), THA (IV TXA vs topical/oral TXA), TKA/THA (IV TXA vs topical/oral TXA) and liver surgery.
The evidence for TXA using in TKA (TXA vs placebo), THA (TXA vs placebo; combine administration vs single administration), TKA/THA (combine administration vs single administration), postpartum bleeding, orthopaedic surgery, shoulder arthroplasty was assessed as probable for the association of reducing transfusion rate. The evidence for TXA using in TKA/THA (TXA vs placebo), liver surgery, spinal surgery, hip fracture surgery, cancer, cardiac surgery was considered to be possible for the association of reducing transfusion rate. There was probably no association between TXA and transfusion rate in TKA (combine administration vs single administration; IV TXA vs topical/oral TXA), THA (IV TXA vs topical/oral TXA), TKA/THA (IV TXA vs topical/oral TXA), trauma, intertrochanteric fractures, gastrointestinal bleeding, plastic surgery, myomectomy.
The evidence for TXA using in intertrochanteric fractures, orthopaedic surgery, hip fracture surgery was assessed as probable for the association of reducing Hb drop. The evidence for TXA using in TKA (TXA vs placebo; combine administration vs single administration), THA (TXA vs placebo; combine administration vs single administration), TKA/THA (TXA vs placebo; combine administration vs single administration), postpartum bleeding, shoulder arthroplasty was considered to be possible for the association of reducing Hb drop. There was probably no association between TXA and Hb drop in TKA (IV TXA vs topical TXA), THA (IV TXA vs topical TXA), TKA/THA (IV TXA vs topical TXA).
The evidence for TXA using in trauma, gastrointestinal bleeding was assessed as probable for the association of reducing mortality. There was probably no association between TXA and mortality in liver surgery, cardiac surgery.
There was probably no association between TXA and DVT in TKA, THA, TKA/THA, postpartum bleeding, intertrochanteric fractures, orthopaedic surgery, spinal surgery, shoulder arthroplasty, liver surgery, trauma, gastrointestinal bleeding, cardiac surgery.
There was probably no association between TXA and PE in TKA, THA, trauma, intertrochanteric fractures, cardiac surgery.
Several other associations were found, but were often affected by heterogeneity or potential confounding factors.