Cancer-Associated Thrombosis: A Two-Way Street

Abstract

Pathological activation of the coagulation system occurs with virtually all forms of cancer, particularly epithelial malignancies. Accordingly, thrombosis is one of the most common comorbidities associated with cancer. Indeed, cancer-associated thromboembolism is the second leading cause of death for cancer patients, second only to the cancer itself. The identification of specific molecular mechanisms whereby tumor cells activate the coagulation system and drive thrombosis has been an active area of investigation for several decades. Studies in animal models and human trials have revealed that there is a bidirectional relationship between coagulation factor activity and cancer, whereby the pathological hemostatic system activation associated with cancer not only promotes thromboembolism but also drives progression of the malignancy. Numerous studies indicate that factors up and down the clotting cascade can contribute to various stages of cancer, including tumorigenesis, primary tumor growth, and metastasis. Although there are some mechanistic points of commonality, there are also clearly context-dependent contributions of coagulation components to cancer progression dependent on the type of cancer and stage of disease. It is also notable that in some instances, coagulation factors appear to contribute to cancer progression independently of their traditional roles in hemostasis and thrombosis. Here, the authors review the current state of the field with regard to hemostatic factor-driven cancer pathogenesis.

Mean platelet volume in arterial and venous thrombotic disorders

“…Beyond frankly thrombotic pathologies, the recent meta-analysis performed by Pyo and colleagues also concluded that MPV is significantly increased in cancer patients compared to healthy controls (mean difference, 0.50 fL; 95% CI, 0.28-0.72 fL), whilst its value significantly decreases in post-treatment patients [44]. This is an important information that contributes to explain the considerably higher burden of thrombotic disorders in patients with malignant diseases [45], as well as the putative interplay between platelet and cancer biology [46].…”

Thrombosis and Hemostasis Issues in Cancer Patients with COVID-19

“…Venous thromboembolism (VTE) events are common among cancer patients, and their occurrence contributes significantly to morbidity and mortality. 8,9 The risk of VTE is increased by fiveto sevenfold among patients with malignant diseases, while fatal PE is three times more common in this population relative to noncancer patients. Annually, 0.5% of cancer patients experience thrombosis compared with a 0.1% incidence rate in general population.…”

Thrombotic microangiopathy in cancer patients

“…Взаимодействие между опухолевой тканью, системой гемостаза и иммунной системой происходит по типу каскада взаимной активации, тем самым приводя к формированию порочного круга. Прикрепляясь к сосудистому эндотелию, опухолевые клетки, активируют коагуляционный каскад напрямую посредством тканевого фактора, а также индукции воспалительных цитокинов [22,25,26]. Активация тромбином активируемых протеазами рецепторов может привести к пролиферации субинтимы эндотелия и гладких мышц.…”