The Association between Tissue Factor-Exposing Microparticles and the Activation of the Coagulation System in Cancer Patients.

Background: Malignancy is a major risk factor of venous thromboembolism. In addition to circumstantial factors such as chemotherapy, the pathogenesis of thrombosis in cancer patients is directly influenced by tumor related factors. In this respect, the expression of tissue factor (TF) on tumor cells is considered to play an important role. Besides its cellular expression, more recent studies focused on TF exposure on circulating microparticles. The role of these TF exposing microparticles with regard to the pathogenesis of VTE in cancer patients, however, has not yet been investigated. We therefore conducted a prospective case control study in order to determine (a) the number and cellular origin of TF exposing microparticles in cancer patients and (b) the association between these microparticles and the activation of the coagulation system.

Materials and Methods: A total of 20 patients with advanced colorectal cancer (Dukes D) and 20 healthy, age- and sex-matched controls were included. Microparticles were isolated from plasma, stained with annexin V, cell-specific antibodies and analysed by flow cytometry. The activation of the coagulation system was measured by D-dimer (ELISA).

Results: Compared to the controls, the total number of TF exposing microparticles was significantly higher in the patient group (32.5 ± 23.9 vs. 18.1 ± 10.0 k/ml plasma, p = 0.007). These finding was due to a higher number of TF exposing microparticles originating from thrombocytes (12.9 ± 7.9 vs. 6.5 ± 2.9 k/ml plasma, p = 0.017) and from monocytes (9.1 ± 6.5 vs. 5.5 ± 1.4 k/ml plasma, p = 0.11) in cancer patients. Likewise, D-Dimer levels were higher among cancer patients as compared to the controls (1.61 ± 1.58 vs. 0.40 ± 0.36 μg/ml, p = 0.001). The number of TF exposing microparticles correlated with D-dimer (r = 0.67, p < 0.001).

Conclusion: Both the significant elevation of TF exposing microparticles in the circulation of cancer patients and the association between these microparticles and the activation of the coagulation system suggest a potential role of TF exposing microparticles in the pathogenesis of venous thromboembolism in cancer patients.