Cancer-associated thrombosis (CAT) is a well–known complication of cancer, especially pancreatic cancer. One possible cause of CAT is secretion of tissue factor (TF)-positive extracellular vesicles from cancer cells. The previous cohort of Western countries showed that patients (pts) with a high level of TF tended to develop CAT with 20–40% incidence in pancreatic cancer. This prospective cohort study aimed to assess the efficacy of TF level for predicting the incidence of CAT in Japanese pts with pancreatic cancer.
We registered consented 197 pts from June 2013 to November 2016, who had pathologically confirmed pancreatic cancer and no history of treatment for the current disease. Plasma samples were collected from pts at the time of registration, 3, 6, and 12 months after. The TF level was evaluated using the Quantikine® ELISA kit (R&D systems) as we found that TF levels in multiple cancer cell lines evaluated using this kit correlated well with those analyzed by western blotting experiments. We estimated the positive (PPV) and negative predictive values (NPV) for the incidence of CAT by using obtained plasma TF levels (cutoff value: 100 pg/ml) and D-dimer levels (cutoff value: 1.2 μg/ml).
Of all the patients, 189 patients were with unresectable disease. The median of the initial level of TF for these pts was 47.8 pg/ml (range: 0.0—318.7). The incidence of CAT was observed in 13 pts (6.6%) at the median follow-up time of 325 days. The median TF level at the time of registration was 148.5 pg/ml in CAT+ group and 53.5 pg/ml in CAT- group with a p–value of < 0.0001. PPV and NPV estimated by TF levels at the time of registration were 23.1% and 94.6%, and by the D-dimer levels were 7.2% and 92.4%, respectively. In pts with a D-dimer level >1.2 µg/ml, NPV by TF < 100 pg/ml was 95%. Similar results were obtained when TF levels of 3 months before the onset of CAT were used.
Present study revealed that the incidence of CAT in Japanese pts was lower than that of Western countries. It was also found that TF levels alone could not predict CAT observed in Japanese pts with pancreatic cancer: however, TF levels were found to contribute to high NPV even in pts with a high level of D–dimer.
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All authors have declared no conflicts of interest.