Using blood and PE markers is useful for distinguishing TPEs from AD-MPEs, such as adenosine deaminase and carcinoembryonic antigen [13,14]. A number of markers can be used to predict TPEs and AD-MPEs, although their use of markers is considerably less specific than histology. However, the results can complement each other [15]. As a routine diagnostic work-up, PT, FIB, FDP and D-D are often used to manage coagulation and fibrinolysis in patients; however, this is the first study to utilize coagulation indicators to distinguish TPEs from AD-MPEs.
Many studies on coagulation function and tumors have found that coagulation indicators, especially FIB, FDP and D-D, are useful for predicting the risk of occurrence, progression, metastasis, and prognosis of lung cancer: Piccioli [16] found that the probability of thromboembolism in patients with tumors was close to 10%; Aminian et al. [17] found that the hypercoagulable state of tumor patients was closely related to cancer progression and prognosis; Palumbo et al. [18] found that FIB and platelets can increasethe possibility of tumor invasion by impeding natural killer cell-mediated elimination of tumor cells during tumor progression. However, there are few reports on the role of coagulation indicators in individuals with tuberculosis [19,20], and there are even fewer reports on coagulation indicators in relation to TPE [21].Therefore, at the outset of this study, we hypothesized that the severity of coagulation dysfunction in patients with AD-MPE swould be more marked than in those TPEs. However, the result was the opposite of what we expected.This study found that the levels of APTT,PT,FIB,FDP and D-Dwere higher, and abnormal patterns were more prevalent in patients with TPEs than in those withAD-MPEs. The results suggest that the severity of coagulation dysfunction is more marked in individuals with benign TPEs than in those with AD-MPEs.
It has been reported that tissue factors are activated and released during acute infection of tuberculosis [22]. As the initiating factor of the endogenous coagulation pathway, tissue factor plays a very important role. PT is the primary indicator with which to monitor the endogenous coagulation pathway [23]. However,there have been no reports on the application of PT to monitor the changes of coagulation function in patients with TPE. In this study, it was found that >70% of the patients with TPE had a high PT. whereas <50% of patients with AD-MPE had a high PT, and this difference was statistically significant. This result differs from the consensus perception that lung cancer, especially lung adenocarcinoma, is more likely to cause coagulation dysfunction [24]. Therefore. in clinical practice, attention should be paid not only to FDP and D-D, but also to PT when acute tuberculosis is suspected.
When Mycobacterium tuberculosis invades the pleura, it activates the monocyte macrophage system and the bacteria are swallowed and degraded by macrophages. The degradation products induce a strong specific allergic reaction and destroy vascular endothelial cells [25]. Progress of lung adenocarcinoma leads to the destruction and disintegration of the tissue, resulting in non-specific inflammatory reactions and inflammatory mediators. The continuous inflammatory state constitutes the microenvironment of tumor progress [26]. About 90% of patients with malignant tumors have vascular endothelial cell injury, and this is most marked in people with lung adenocarcinoma [27]. The damage to vascular endothelium caused by pleural effusions can destroy the balance of the coagulation and fibrinolysis systems. For this reason, this study considered all possible abnormal patterns of coagulation function indicators in the two groups, and ten patterns of abnormal coagulation function caused by AD-MPE and TPE, which not only confirmed the results of previous studies, but also reflected the complexity of the two conditions. In this study, simultaneous abnormalities of PT, FIB, FDP and D-D,and PT, FDP and D-D,were present in 44% and 23%of patients with TPE, which was higher than the 10% of these abnormalities in patients with AD-MPE(P<0.05). These results indicate that clinicians should consider the possibility of TPE in patients with pleural effusions who have either of these two abnormal patterns of coagulation function indicators.
As degradation products of cross-linked fibrin, FDP and D-D are considered to be general indicators of coagulation activation and fibrinolysis [28-30]. In this study, FDP and D-D were the two indicators with the highest diagnostic performance, and FIB had the highest sensitivity, but their YIs, which are based on the sensitivity and specificity of the test were less than 0.5. Therefore, in order to improve the power of these indicators to distinguish between AD-MPE and TPE, we combined PT, FIB, FDP and D-Dto create a joint indicator.ROC curve analysis showed that the diagnostic performance of the combined indicator was better than that of any of the indicators alone. Therefore, although the determination of coagulation function is the most basic method for the differential diagnosis of AD-MPE and TPE, it had the characteristics of simplicity, economy, rapidity and is non-invasive, and is suitable for use in limited-resource settings and in community-based health facilities as an ideal way to distinguish TPE from AD-MPE.
The primary limitation of this study was that participation was restricted to patients withAD-MPEsor TPEs, and patients with lung cancer and tuberculosis without pleural effusions were excluded.We are planning to conduct a further study with a larger sample size that takes into account the pathological classification of lung cancer, incorporates more types of tuberculosis, and reduces bias as far as possible, to further explore the value of using coagulation indicators in different pathological types of lung cancer and different types of tuberculosis.