The aim of this study was to explore the difference in activated partial thromboplastin time (APTT) levels in patients with tuberculous and non-tuberculous pleural effusion (TPE and non-TPE) and its possible mechanism to provide a new direction for the diagnosis of pleural effusion (PE).
A total of 61 patients diagnosed with tuberculous pleurisy with pleural effusion at Shunde Hospital of Southern Medical University from July 2013 to September 2020 were selected as the observation group (tuberculosis group). Another 89 patients (45 with malignant pleural effusion (MPE) and 44 with parapneumonic pleural effusion (PPE) composed the control group. The adenosine deaminase (ADA) level in pleural fluid and plasma APTT level were measured in the two groups.
The levels of APTT and ADA in the TPE group were significantly higher than the control group, and were 40.03 (37.00, 42.60) (s) and 55.00 (47.00, 69.25) (U/L) for TPE, 29.50 (25.45, 34.20) (s) and 11.90 (9.15, 19.05) (U/L) for malignant pleural effusion (MPE) and 31.35 (27.43, 35.76) (s) and 15.15 (7.40, 35.00) (U/L) for parapneumonic pleural effusion (PPE), respectively.
The level of plasma APTT has certain significance in differentiating tuberculous pleural effusion from nontuberculous pleural effusion.
Tuberculosis pleural effusion (TPE) is considered to be one of the most prevalent types of pleural effusion (49.6%), followed by malignant pleural effusion (MPE) (29.6%) and other types of pleural effusion (e.g., parapneumonic pleural effusion (PPE)).
Because of similar clinical symptoms among the various types of pleural effusion, the diagnostic process of the aetiology is often a challenge for medical practitioners. Besides, differences in therapy and prognosis are obvious among various types of pleural effusions (PEs) to some degree. As a result, confirmation of the aetiology of PEs is indispensable in the clinic. Though biopsy of the tissue from the pleura by means of medical thoracoscopy is able to directly provide a pathological appearance that contributes to the identification of the type of pleural effusion, it inevitably causes some complications, such as trauma or infection. In contrast, biomarkers such as interleukin 27 (IL-27), adenosine deaminase (ADA) and tumor necrosis factor-α (TNF-α) have been widely recognized for their satisfactory capacity and less invasive interference utilized in the diagnosis of TPE. However, limitations that originate from the biomarkers themselves have still been found in research on further development. Previous studies have performed several analyses based on the relationship between age and the concentration of ADA and found that a negative relationship exists, indicating that the level of ADA decreases with increasing age. The cut-off level of ADA for the diagnosis of TPE in the older group and for the younger group was 25.9-26 IU/I vs 49.1-72 IU/I, respectively. 10 In addition, an appropriate threshold range for IL-27 to discriminate TPE from other types of pleural effusions has still not been identified. Therefore, it is still necessary to find new biomarkers for the qualitative diagnosis of pleural effusion. Activated partial thromboplastin time (APTT), which is calculated depending on the time required for clot formation after adding an activating reagent to plasma, is a sensitive index that reflects the function of the endogenous coagulation system. The link between pulmonary tuberculosis and coagulation function is strong. The inflammatory reaction attributed to tuberculosis infection is able to activate and regulate the coagulation system by secreting a number of inflammatory factors to establish an advantageous environment for resisting damage induced by pathogenic germs. It has been reported that the risk of disseminated intravascular coagulation (DIC) will increase in patients with pulmonary tuberculosis, which was almost 3.2%. Similar findings have also been reported for hyperfibrinogenaemia.
TPE can be viewed as a result triggered by tuberculosis infection in the pleura, and a similar connection may exist between TPE and APTT to make it possible for APTT to be used as a biomarker in discriminating TPE from other PEs.
According to existing studies on TB and the coagulation system, there are several possible mechanisms for the link between APTT and TPE: (1) Patients with TPE have an activated immune response of T lymphocytes, which contributes to its enhancement of proliferation and differentiation. With the negative feedback reaction occurring, the level of ADA will increase to promote the deamination of adenosine to reduce its inhibition of T lymphocytes.
The conversion of adenosine into hypoxanthine nucleoside will be accelerated due to the elevation of the concentration of ADA and indirectly induce the reduction in adenosine triphosphate (ATP) levels. As a result, the main energy source of red blood cells will be depleted, followed by loss of membrane stability, thus causing the destruction of the cell membrane and triggering the occurrence of hemolysis. During the process of hemolysis, lipids in red blood cells are released to promote the occurrence of coagulation for the sake of the dissolution of red blood cells. With the process of coagulation, the consumption of blood coagulation factor will be maintained and ultimately induce an increase in the level of APTT. (2) The coagulation system and secretion of C protein will be activated to establish an advantageous condition for resistance to pathogens such as tuberculosis due to the production of inflammatory reactions.
Similarly, the number of blood coagulation factors will decrease owing to utilization during the process of activation of the coagulation system and cause the elevation of APTT levels.
To our knowledge, the diagnostic accuracy of APTT in TPE, as well as the relationship between APTT and TPE, have not been sufficiently evaluated. In the present study, we aimed to explore the potential of APTT as a biomarker for the diagnosis of TPE in tandem with their potential relationships by comparing the level of APTT and ADA in PE patients with TPE and non-TPE.