Plenty of studies have revealed the close association between coagulation and infection. Many researchers believed, endotoxins or components of the bacterial cell wall can trigger changes in coagulation through tissue factor (TF) released by a variety of cells, such as vascular endothelial cells and monocytes, and maintain TF in high expression by stimulating the release of cytokines, such as interleukins (ILs) and tumor necrosis factor α (TNFα) [21, 26, 27]. Correspondingly, coagulation-related biomarkers, have recently been proved as valuable markers in the diagnosis of PJI. Geng Bin et al.  reported fibrinogen as a promising marker to aid in diagnosing PJI. Wu Hao et al.  demonstrated fibrinogen exhibits pretty value in PJI diagnosis. D-Dimer has been adopted as a minor criterion in the 2018 International Consensus Meeting (ICM) criteria for PJI, but it raised a hot debate after that. Qian Hu et al.  and Leilei Qin et al.  found D-Dimer is a valuable test for PJI diagnosing. Jiren Yan et al.  led a meta-analysis and found that D-Dimer is an effective serum biomarker for PJI diagnosis in patients without a history of hypercoagulation disease or inflammatory arthritis. While Tejbir et al.  and Rui Li et al.  reported D-Dimer has a poor diagnostic value for PJI. Lauren et al.  found D-Dimer results vary significantly in different laboratories, even for the same sample, so they disagreed D-Dimer as a PJI diagnosis criterion. In our study, D-Dimer exhibited a low value in PJI diagnosing, and its numerical values were still high after ESR and CRP were decreased in the normal range.
However, these conventional coagulation biomarkers can only reflect the quantitative changes of platelet and fibrinogen. TEG is measuring all coagulation proteins and cellular elements on clot formation; it can trace the whole coagulation process from the beginning of coagulation to the lysis of blood clots and show the whole process in a form of a graph . TEG has been widely applied in monitoring hemostasis during cardiac surgery and liver transplant procedures , guiding transfusion requirements in trauma patients, and during surgery and assessing septic coagulopathy in severely ill patients . TEG can provide comprehensive coagulation status of our body, and provides additional data compared with standard coagulation tests . Many studies have compared TEG and conventional coagulation tests in many clinical fields. Hani et al.  demonstrated TEG provides more information about the hemostatic state of patients with cirrhosis more than that of conventional coagulation tests. Cuizhu Luo et al.  reported TEG may be a reliable alternative to conventional coagulation methods for diagnosing sepsis-induced coagulopathy.
There is no study evaluating TEG’s value in diagnosing PJI yet. Thus, we conducted the study to compare the value of TEG with the three most used biomarkers (CRP, ESR, and D-Dimer) in diagnosing PJI. In the present study, we highlight the value of ESR in diagnosing PJI, with AUC, the optimal cutoff, sensitivity, and specificity for ESR were 0.953, 34.0mm/h, 81.82%, and 94.87%. D-Dimer has the smallest AUC, and it is still high in PJI patients before the second stage surgery. The results are similar to several other studies [11, 12, 29], though small differences in the numerical value of AUC, cutoff value, sensitivity, and specificity. To the best of our knowledge, no study before has reported the value of TEG in the diagnosis of PJI. Our study found MA achieved a pretty good diagnosis value, with a specificity was 97.44%. And the combination of CRP/ESR with TEG parameters (K, Angle, MA, A30, TPI) achieved higher sensitivity and specificity than any individual, except for the two combinations (ESR + MA, ESR + A30). Although AUCs of these parameters were smaller than ESR, TEG is still a promising diagnosis testing for PJI.
Performing the second-stage revision in proper timing is the key to boost the success rate of PJI treatment. To find the best timing for re-implantation, researchers worldwide have never stopped exploring. In recent years, various indicators have been reported. Hoell et al.  reported CRP was not a reliable parameter to exclude persistent infection. Tao Bian et al.  also concluded that ESR and CRP were of limited value in determining reimplantation timing by pooled analysis. And some researchers found coagulation-related biomarkers performed well in guiding reimplantation. Alisina Shahi et al.  highlighted D-Dimer in determining the optimal timing of reimplantation. And Geng Bin  reported fibrinogen is a useful tool in assessing infection outcomes after first-stage surgery. But a small sample of both studies limited their credibility. In our study, we found that ESR and MA were good indicators in determining reimplantation timing. Our study showed a 100% success rate of two-stage revision, which is higher than most published studies. Several reasons are contributing to this result: 1) follow-up time of 4 patients were shorter than 1 year, which may be not enough to judge the control of infection. 2) Although widely adopted by many researchers, Delphi-based consensus was not the golden standard for evaluating the success of the two-stage revision. It overlooks the functional outcome of the surgery. When taken the function outcome, our success rate would be lower.
According to the results of the study, TEG appears to have the following advantages. First, as a regular and routine serological testing for coagulation, the TEG test does not bring additional costs or suffering to patients. Second, TEG parameters may be applied to differentiate PJI from aseptic loosening, especially the combination of CRP with MA/A30. Finally, MA/A30 appears to be a useful tool in assessing infection control after spacers insertion.
Our study has several limitations. Firstly, the samples in this study were too small, a larger sample size might have produced different results. Secondly, lower extremity Doppler ultrasound was routinely performed to exclude venous thromboembolism of the lower limb, which didn’t rule out clots in a different portion of the patient’s body. If clots undetected have existed in Group A, the diagnostic value of studied parameters would be overestimated. While if in Group B, the influence would be reversed. Moreover, we did not consider the use of antibiotics of PJI patients before admission to our hospital. Furthermore, the study has some inherent biases of a retrospective study. Last but not least, we only checked the TEG of PJI patients before spacers insertion and before reimplantation, rather than checked them regularly. Hence, the changing trend of these biomarkers’ levels in patients with PJI is not clear.