In this study, we found that the coagulation profile in PJI patients was different from that in non-PJI patients and PJI patients can suffer from subclinical abnormal coagulation profile. In consistent with previous reports, some coagulation markers such as plasma D-dimer and fibrinogen show promising PJI diagnostic values. Besides, we also revealed a few new markers (APTT, INR and platelet count) for PJI diagnosis from the coagulation profile in PJI patients. Then we build a logistic model based on these 3 markers and the ROC analysis suggested this model was promising in PJI diagnosis.
PJI indicating that infection occurs to the prosthesis and surrounding tissues is one of the most disastrous complications after TJA and its pathogens are known to impair their host by secreting endotoxin and exotoxin which can stimulate CD8 + T cells and antigen-presenting cells (APC) to produce various cytokines[8]. These cytokines (IL-1, TNFα, and IL-6) can disrupt normal coagulation cascade and subsequently cause abnormal coagulation profile[14–16]. However, a review of literature suggests that the coagulation profile in PJI patients remain unknown. This study evaluated the change of coagulation profile in PJI patients.
In the presence of chronic infection, large amounts of endothelial cells can be disrupted and following cytokines and tissue factors will be released into the blood. Then coagulation system and following fibrinogen system can be activated[17]. Eventually, the body will delete excessive coagulation factors such as antithrombotic factors, TFPI (tissue factor pathway inhibitor) for hemostasis[18, 19]. Then, following coagulopathy may appear in PJI patients.
The levels of APTT, INR, D-dimer, plasma fibrinogen, platelet count in the PJI group is significantly higher than that in non-PJI group. Despite relatively higher levels of APTT and INR, the levels of these two markers is still within clinical reference values. It suggests that PJI patients are suffering from subclinical abnormal coagulation. The levels of APTT and INR in PJI group is significantly higher than that in non-PJI group but the level of TT between the two groups is comparative. This condition reveals that the change of coagulation cascade in PJI group is mainly ascribed to the change of intrinsic pathway and extrinsic pathway instead of the common pathway (Fig. 3). Therefore, the coagulation factors participating in the two pathways of coagulation may be different between the two groups. However, this hypothesis needs approving further. And subsequent studies should focus on the change of coagulation factors in PJI patients.
The subclinical coagulation change may have potential influence on increased blood loss in PJI patients[20]. Elevated APTT and INR indicate impaired coagulation system and can cause increased joint effusion after revision. This is consistent with our clinical observation that patients after PJI revisions often have larger drainage volume and longer drainage tube retention time than non-PJI patients. However, the larger joint effusion volume can increase the likelihood of PJI recurrence conversely. It can be paradoxical when doctors try to hold the balance between the abnormal coagulation and VTE in PJI patients after revision. Besides, vitamin K and FFP which is often used in the treatment of patients with coagulopathies are associated with severe reactions such as allergy.[21] Therefore, correcting the abnormal coagulation in PJI patients may be a challenging work. And the association between abnormal coagulation profile and the outcomes of PJI need to be explored further.
The level of APTT and INR in PJI patients is significantly higher than that in non-PJI patients. It means that PJI patients suffer from hypocoagulation compared to non-PJI patients. In [8], Parvizi reveled similar results. Despite a fact that most coagulation indictors were still within clinical reference values, we do hold the opinion that the subclinical coagulation profile still causes some abnormalities. The use of regional anesthesia in these patients can increase the risk of epidural or spinal hematoma formation theoretically. And hypocoagulation may impair incision healing after surgery.
In this study, we also evaluated the use of coagulation profile for PJI diagnosis. We found that APTT, platelet count, plasma fibrinogen and D-dimer can play a role in the diagnosis of PJI. The use of D-dimer for the diagnosis of PJI have been introduced into the 2018ICM criteria and the application of plasma fibrinogen and platelet count in PJI diagnosis has also been revealed by several studies[10, 11]. But the accuracy of APTT has not been studied in suspected PJI patients. In our research, we found that plasma fibrinogen performed better than D-dimer and plasma fibrinogen when these markers were evaluated. It is consistent with previous studies and suggests that plasma fibrinogen can be a better marker than D-dimer[10, 12]. Besides, although platelet count and the level of APTT had inferior diagnostic value compared with CRP, ESR, plasma fibrinogen and D-dimer, they can be useful for the diagnosis of PJI.
To further assess the performance of coagulation profile in PJI diagnosis, a logistic model was built based on significantly up-regulated coagulation indicators in PJI patients (APTT, plasma fibrinogen, D-dimer, and platelet count). And this model performed better than CRP and ESR in the diagnosis of PJI. This result suggested that the coagulation profile can be used as a screening tool in suspected PJI patients because this is a routine test before surgery and the corresponding cost is relatively low. Besides, this test can be performed in most hospitals. It makes this test become a simple screening tool for PJI diagnosis in primary hospital.
This study also has several limitations. First, even though the relationship between the coagulation profile and PJI was revealed by our study, we can’t assess the change of certain coagulation factors because of limited medical information. Second, this was a retrospective study performed in a single center so the study design and absent in medical records can lead to selection bias. Besides, it is hard for us to discern the causal link between PJI and abnormal coagulation profiles. Third, some patients with systemic diseases (kidney disease, liver diseases and systemic inflammatory diseases e.g.) were not excluded from this study[22]. These conditions can influence the coagulation profile of PJI patients. However, the heterogeneous cohorts can also provide a more realistic clinical situation for the evaluation of the coagulation profile in PJI patients.