Thromboelastography Characterizes the Hypercoagulable State in Murine and Human Breast Cancer

血栓弹力图可用于表征小鼠和人类乳腺癌的高凝状态

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Abstract

BACKGROUND: Breast cancer is associated with an increased risk of cancer-associated thrombus (CAT), which is linked to worsened prognosis. Despite malignancy being a known risk factor for hypercoagulability, methods to quantify the pro-thrombotic state and stratify patients are lacking. The goal of our study is to utilize whole blood TEG to quantify a hypercoagulable state in breast cancer murine models and patients. METHODS: Citrated whole blood was obtained for TEG analysis from polyoma middle tumor-antigen (PyMT) transgenic mice, who develop spontaneous breast tumors, their age-matched control litter mates, and newly diagnosed, untreated breast cancer patients seen in our multi-disciplinary clinic. Blood samples were placed in disposable cups without heparinase. Calcium chloride was added to reverse effects of sodium citrate. Values for R (min), K (min), alpha angle (degrees), maximum amplitude (MA, mm), coagulation index (CI), and lysis 30 (LY30) were analyzed. RESULTS: PyMT mice demonstrated elevated MA levels relative to age-matched controls, with a stepwise increase observed with advancing breast cancer stages. CI was significantly elevated in stage II through stage IV. Patient correlative samples also exhibited a hypercoagulable state across all invasive stages, as well as in ductal carcinoma in situ, characterized by increased R, alpha angle, and CI values, alongside a reduction in K. Stage IV patients exhibited an elevated MA. Estrogen receptor status did not impact TEG parameters. Four patients developed CAT. CONCLUSION: TEG effectively identified hypercoagulability in murine and human breast cancer, normalized by aspirin in mice. This supports TEG's potential for dynamic CAT risk stratification for personalized prophylaxis.

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