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

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.

Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN trial

“…Coagulation activation is intimately related to tumor development, which has been mechanistically linked to the induction of tissue factor (TF), i.e. the main initiator of coagulation [ 5 , 6 ]. Low-molecular-weight heparin (LMWH) binds to antithrombin-III and potentiates its inhibition of procoagulant factor Xa [ 7 ].…”

Gradient Infiltration of Neutrophil Extracellular Traps in Colon Cancer and Evidence for Their Involvement in Tumour Growth

“…Moreover, Tissue factor (TF) the main in vivo initiator of coagulation has been reported to play a key role in cancer biology [ 20 , 21 ]). TF-thrombin axis, apart from its implication in cancer-associated thrombosis, has been indicated to have a very potent angiogenic property via signaling of its serine proteases through PARs.…”

Prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies: validation of the Khorana Risk Score

“…Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent complication in patients with cancer, and it is associated with increased morbidity and mortality [ 1 , 2 ]. Based on selected biomarkers and clinical factors, some VTE assessment models for chemotherapy-associated thrombosis were proposed [ 3 – 8 ].…”