Most patients with solid tumors have different degrees of abnormal coagulation function, including conditions such as hyperfibrinolysis, hemostatic dysfunction, abnormal coagulation function, or abnormal platelet activation.10 In severe cases, this can lead to the formation of peripheral venous thrombosis,11 affecting clinical outcomes and prognoses in patients with cancer.
D-dimer—a molecular marker with specificity for fibrinolysis—is formed by the cleavage of cross-linked fibrinase, and its plasma concentration can directly reflect the coagulation state of the body. Therefore, D-dimer is widely used to diagnose disseminated intravascular coagulation, myocardial infarction, and thromboembolism.12
Our study aimed to expand on this understanding by investigating the potential of D-dimer as a specific marker in patients with esophageal cancer. Our findings suggest that individuals with esophageal cancer exhibit a hypercoagulable state and heightened fibrinolysis, indicating the potential of D-dimer as a biomarker for this disease. Plasma D-dimer levels are a promising reference point for diagnosing esophageal cancer for several reasons. First, solid malignant tumors cause varying degrees of necrosis in surrounding healthy cells, releasing procoagulant substances into the bloodstream. This abnormal coagulation cascade leads to elevated levels of D-dimer in peripheral plasma.13 Second, esophageal cancer is often diagnosed in the middle and late stages of progression. Patients experience malnutrition, emaciation, and cachexia, slowing peripheral venous blood flow and causing blood stasis. Third, tumor cells stimulate the release of procoagulant factors within the body, generating thrombin and accelerating fibrin degradation. This dynamic affects the overall coagulation function, pushing the body toward a hypercoagulable state.14 Fourth, eliminating tumor cells triggers the release of procoagulant factors by natural killer cells, impacting coagulation processes.14 Conversely, continuous tumor cell consumption, coupled with a decline in immune function, hinders the synthesis of blood coagulation factors and increases the risk of secondary hemorrhage.13
In patients with stage III–IVA esophageal cancer, the preoperative D-dimer level was 0.92 ± 1.149 µg/mL, significantly higher than that in patients with stage I–II of the disease. This escalation in D-dimer levels suggests a correlation between esophageal cancer progression and increased hypercoagulability. This observation aligns with the work of Qifeng et al.15, as tumor cells can disrupt blood vessel integrity during invasion, leading to hemorrhagic changes that activate the coagulation cascade and result in higher D-dimer levels.16 Additionally, the hypercoagulable state of the blood promotes tumor cell mobility and metastasis, thereby accelerating the replication of tumor cells.17 Activating factors, such as the tissue factor present in patients’ blood, induce thrombi formation, cell proliferation, and angiogenesis by affecting cell signaling pathways, facilitating the adhesion and proliferation of tumor cells.18 In addition, the abnormal increase in D-dimer concentration can lead to blood stasis and provide a conducive environment for the hematogenous metastasis of tumor cells.19 Consequently, a reciprocal cycle between tumor progression and the coagulation system ensues, further emphasizing the potential significance of anticoagulant therapy in managing the risk of metastasis and recurrence.20
Limitations
This study had some limitations. This was a single-center study with a relatively small sample size and short-term follow-up. Therefore, further validation of the results is necessary. Future steps involve expanding this research to other hospitals and conducting a statistical analysis of the 5-year postsurgical survival rate. The aim is to encompass a cohort of 60 patients with early esophageal cancer (cT1N0M0), measuring peripheral plasma D-dimer levels alongside tumor markers like carcinoembryonic antigen to establish a more comprehensive understanding of D-dimer's diagnostic value.