Thrombotic Pathogenesis and Laboratory Diagnosis in Cancer Patients, An Update

Abstract

Cancer-associated thrombosis (CAT) is a leading cause of mortality in cancer patients and its incidence varies in different parts of the world. Venous thromboembolism (VTE) is a prominent manifestation of CAT, and significantly impacts morbidity and survival compared to arterial thrombosis in cancer patients. Several risk factors for developing VTE such as chemotherapy and immobilization have also been found co-existing with cancer patients and contributing to the increased risk of VTE in cancer patients than in non-cancer patients. This review highlights recent mechanisms in the pathogenesis of hypercoagulable syndromes associated with cancer, multiple mechanisms implicated in promoting cancer-associated thrombosis and their diagnostic approaches. Cancer cells interact with every part of the hemostatic system; generating their own procoagulant factors, through stimulation of the prothrombotic properties of other blood cell components or the initiation of clotting by cancer therapies which can all directly activate the coagulation cascade and contribute to the VTE experienced in CAT. It is our hope that the multiple interconnections between the hemostatic system and cancer biology and the improved biomarkers reported in this study can be relevant in establishing a predictive model for VTE, optimize early detection of asymptomatic microthrombosis for more personalized prophylactic strategies and incorporate effective therapeutic options and patient management to reduce mortality and morbidity, and improve the quality of life of affected cancer patients.

Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective

“…This induced expression of TGF-β1 in cancer cells, along with the enhanced expression of enzymes (plasmin, MMPs) and other cancer-associated triggers that activate latent TGF-β1 (integrins and TSP-1, ROS), as described earlier, serve tumors with elevated levels of active TGF-β1 that aid cancer cells to grow, survive, and metastasize. Moreover, as will be covered later in detail, carcinomas promote a hypercoagulable state in the host, leading to enhanced thrombosis [ 328 ], which results in the release and activation of platelet TGF-β1 as well as other platelet growth factors. The importance of this cannot be overstated, given that patients with cancer have a 9-fold increased risk of venous thromboembolism, which is also the second leading cause of cancer deaths [ 328 ].…”

“…Moreover, as will be covered later in detail, carcinomas promote a hypercoagulable state in the host, leading to enhanced thrombosis [ 328 ], which results in the release and activation of platelet TGF-β1 as well as other platelet growth factors. The importance of this cannot be overstated, given that patients with cancer have a 9-fold increased risk of venous thromboembolism, which is also the second leading cause of cancer deaths [ 328 ].…”

“…Due to their hypercoagulable state, many cancer patients are given antithrombotic drugs [ 328 ]. A common anticoagulant given to cancer patients is low molecular weight heparin (LMWH), which has been reported to inhibit tumor metastasis [ 366 ].…”

The Potential of Integrative Cancer Treatment Using Melatonin and the Challenge of Heterogeneity in Population-Based Studies: A Case Report of Colon Cancer and a Literature Review

“…Venous thromboembolism (VTE) is one of the most common causes of death and morbidity in cancer patients, and CT and immobilization contribute to an increased risk of VTE [76]. The prevalence of coagulopathy, including thrombocytopenia and APTT prolongation, has been shown in patients with CRC [6].…”

Cancer-Associated Thrombosis: Pathophysiology, Laboratory Assessment, and Current Guidelines

“…Cancer cells induce a prothrombotic switch in the host hemostatic system and, vice versa, activation of the hemostatic system stimulates tumor growth and dissemination [28,29]. Patients with cancer are in a constant prothrombotic state, presenting abnormalities in all three components of Virchow's triad [2,4,7,8]. Various pathophysiological pathways have been identified in the interplay between different components of the hemostatic system and cancer.…”