Assessment of hypercoagulability using thromboelastography predicts advanced status in renal cell carcinoma

Abstract Background Thromboelastography (TEG) has been established as a sensitive method to assess the whole coagulation process. The aim of the study was to evaluate the diagnosis significance of TEG on hypercoagulability in patients suffering renal mass. Methods A total of 478 patients were diagnosed with renal tumor by histolopathologic examination and were assigned to three groups. Group A: 79 patients with benign renal tumor; Group B: 317 patients with renal cell carcinoma (RCC, Fuhrman grades I and II); Group C: 82 patients with high‐risk RCC (Fuhrman grades III and IV). Subgroup analysis was performed in malignant renal tumor patients according to the TMN classification. The clinical data, whole blood TEG, and conventional coagulation tests were reviewed. Results There was no statistically significant difference between subgroups in respect to conventional coagulation tests. Hypercoagulablity was marked in Group C according to the TEG parameters. The elevated platelets and fibrinogen is linked with hypercoagulability in renal tumor. The positive correlation was between fibrinogen and MA value (r = .663, P < .05). The pathologic tumor stages were also associated with the TEG parameters. Conclusion Patients suffering advanced RCC are hypercoagulable which can be identified by TEG. MA value could be potential diagnosis indicators for detecting high‐grade RCC.

thromboplastin time (APTT) and prothrombin time (PT), is usually used to evaluate the coagulation status of patients. Several limitations were considered in these tests, including that all these tests are unable to reflect the overview of all aspects of the coagulation process.
Thromboelastography (TEG) was first introduced by Trousseau, and it is a type of graph that depicts the process from the beginning of clot formation to fibrinolysis. 6 It has been established as a sensitive method to assess the entire coagulation process including clotting, platelet activation, kinetics of clot formation, and fibrinolysis. TEG has been widely used in guide transfusion, helping to evaluate the hemostasis function in patients with trauma and solid tumors.
The data concerning the clinical use of TEG in patients with renal tumor are rare. Therefore, we retrospectively reviewed renal mass patients who accepted operation in our clinical center and evaluated the coagulation status in those patients with solid renal mass for the first time using TEG data and conventional coagulation tests. The TEG data were also compared with routine coagulation analysis in order to determine the correlation between the two tests.

| Laboratory assays
All blood tests were implemented within 24 hours before operation.

| RE SULTS
A total of 478 patients were grouped as follows: in MA, α angle, and CI were also found between Group C and the other groups, indicating that hypercoagulability was most evident in Group C (Table 3). In terms of TEG parameters, no difference was observed between Group A and B. The positive correlation was found between fibrinogen and MA value (r = .663, P < .05). There was also a weak correlation between platelet count and MA value (r = .423, P < .05). However, PT and TT failed to significantly correlate with any parameter of TEG. APTT weakly correlated with R time (r = .258, P < .05). As an inflammatory marker, NLR also presented the correlation with K time, alpha angle, and MA value. All results are summarized in Table 4.
During the postoperative period, VTE was identified in 3 people in group B and group C, consisting of 2 PE events and 1 DVT event.
To further analyze the hypercoagulability status of patients with RCC, the patients were additionally categorized into three subgroups according to the TMN classification: Group 1 (286 patients with pT1 tumor), Group B (74 patients with pT2 tumor), and Group 3 (patients with ≥ pT3 tumor) ( Table 5). These three subgroups were also compared with the previously mentioned laboratory parameters. The result showed that the NLR, platelet count, and FIB level were all highest in Group 3. With respect to Groups 1 and 2, the significant decreased value in the R and K times, and the increase in MA, α angle, and CI were found in Group 3 (P < .05). This study also determined that the tumor cells could stimulate endothelial cells to release tissue factor and induce the secretion of fibrinolytic enzymes. 8 The level of FIB, inflammatory factors (IL-6), and D-dimer were found in higher levels for those patients with metastasis. FIB was an important parameter showing the changes of clotting function and angiogenesis. 9 Another study presented that the levels of FIB in patients with RCC were remarkably higher than those with benign renal tumors, where no significant differences were shown between the PT and APTT results. 10  group of patients with high-risk RCC (Fuhrman grades III and IV) and

| D ISCUSS I ON
high-stage RCC (≥pT2 stage) had shorter R and K times, as well as The limitations of the present study include the retrospective analysis of RCC cases and heterogeneity of the series. The results may only reflect a single-center experience. The main goal of our study was to present the coagulation status in patients with RCC. As such, we endeavored to provide evidence that TEG could be applied to evaluate the RCC-induced hypercoagulability status. during disease progression.

CO N FLI C T O F I NTE R E S T S
All authors read and approved the final manuscript. The authors declare that they have no competing interests.

DATA AVA I L A B I L I T Y S TAT E M E N T
The datasets used and analyzed during the current study available from the corresponding author on reasonable request.

E TH I C S A PPROVA L A N D CO N S E NT TO PA RTI CI PATE
Our study was approved by the institutional review board of Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, and the requirement for informed consent was waived.

CO N S ENT PU B LI C ATI O N
Not applicable.