Thromboelastography Characterizes the Hypercoagulable State in Murine and Human Breast Cancer

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.

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.

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.

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.