Cancer Tissue Procoagulant Mechanisms and the Hypercoagulable State of Patients with Cancer

 

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Abstract

Thrombosis is a major cause of morbidity and mortality in cancer patients. Many clinical factors contribute to the high thrombotic risk of this condition, including the type of malignancy, its disease stage, anticancer therapies, and comorbidities. However, the cancer cell-specific prothrombotic properties together with the host cell inflammatory response are important players in the pathogenesis of the cancer-associated hypercoagulability. Tissue factor (TF) is the most important procoagulant protein expressed by cancer cells, and with other cancer tissue procoagulant properties highly contributes to the procoagulant phenotype of malignant cells. Recent discoveries indicate that oncogenes determine the procoagulant protein expression, including TF, in cancer tissues. In addition, in malignancy, TF is also overexpressed by host normal blood cells triggered by cancer-derived inflammatory stimuli. As a consequence, a subclinical activation of blood coagulation is typically present in cancer patients, as demonstrated by abnormalities of circulating thrombotic biomarkers. The relevance of measuring these biomarkers to determine the patient thrombotic risk level is under active investigation. The goal is to identify the high-risk subgroups to establish more accurate and targeted anticoagulation strategies to prevent thrombosis in cancer patients. Ultimately, the clarification of specific molecular mechanisms triggering blood coagulation in specific cancer types may also indicate alternative ways to inhibit clotting activation in these conditions.

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