Cancer-Associated Thrombosis: Risk Factors, Molecular Mechanisms, Future Management

Abstract

Venous thromboembolism (VTE) is a major health problem in patients with cancer. Cancer augments thrombosis and causes cancer-associated thrombosis (CAT) and vice versa thrombosis amplifies cancer progression, termed thrombosis-associated cancer (TAC). Risk factors that lead to CAT and TAC include cancer type, chemotherapy, radiotherapy, hormonal therapy, anti-angiogenesis therapy, surgery, or supportive therapy with hematopoietic growth factors. There are some other factors that have an effect on CAT and TAC such as tissue factor, neutrophil extracellular traps (NETs) released in response to cancer, cancer procoagulant, and cytokines. Oncogenes, estrogen hormone, and thyroid hormone with its integrin αvβ3 receptor promote angiogenesis. Lastly, patient-related factors can play a role in development of thrombosis in cancer. Low-molecular-weight heparin and direct oral anticoagulants (DOACs) are used in VTE prophylaxis and treatment rather than vitamin K antagonist. Now, there are new directions for potential management of VTE in patients with cancer such as euthyroid, blockade of thyroid hormone receptor on integrin αvβ3, sulfated non-anticoagulant heparin, inhibition of NETs and stratifying low and high-risk patients with significant bleeding problems with DOACs.

Implication of Hepsin from primary tumor in the prognosis of colorectal cancer patients

“…Model building was performed by understanding the causal mechanisms or sources of bias in CRC. Thus, the covariates for the multivariate model were chosen on theoretical grounds, following literature review (19)(20)(21)(22)(23)(24), and taking into account expert opinion. In metastatic tumors, the multivariable model for PFS and OS included HPN staining (specified as a three-level categorical variable), Eastern Cooperative Oncology Group (ECOG) performance status, histologic grade, presence of more than one metastatic site, and specific metastatic sites (…”

Risk Prediction Model of Postoperative Venous Thrombosis of Ovarian Cancer

“…shown in Figure 1 and Table 6. [2] .The incidence of postoperative VTE is higher in gynecological patients due to the possible use of hormones, special surgical site and other reasons.In previous studies, perioperative VTE occurred in 38% of patients with gynecologic cancer, much higher than in patients with benign gynecologic surgery (14%) [3] .The incidence of VTE in ovarian cancer patients is the highest among gynecological tumors due to advanced age, multiple internal and surgical complications, late stage of diagnosis, pelvic compression by tumor and large amount of ascites, large surgical range, and long treatment course [4] .Literature has reported that up to 60% of VTE occurs in elderly patients over 70 years old [5] .A retrospective study on the incidence of preoperative VTE in 387 patients with primary ovarian cancer found that the incidence of preoperative VTE and PE were 13.4% and 9.3%, respectively. The risk of preoperative VTE in patients aged ≥60 years was signi cantly higher than that in patients aged < 60 years [5] , which was basically consistent with the results of this study.The reason may be related to the decrease of physical activity and venous pump failure in most elderly patients, and the increase of coagulation promoting factors, such as factor and factor , homocysteine and brinogen with age [5][6] .In addition, in addition to the type and stage of cancer itself, the biggest risk factor for VTE is the presence of two or more potential chronic comorbidities, which are commonly diabetes, hypertension, chronic kidney disease, heart failure and lung disease [7] .Therefore, elderly, obese, hypertensive and diabetic patients should increase physical activity, eat a light diet, control BMI and actively control blood pressure and glucose levels.…”

“…times [8] , which may be related to the direct damage of chemotherapy drugs to endothelial cells, the reduction of endogenous anticoagulants, the increase in the number of pro-coagulant proteins and the enhancement of their activity.In addition, chemotherapy can activate platelets, and may also lead to cell apoptosis and cytokine release, thereby enhancing the expression of tissue factors, resulting in the highly active form of monocyte/macrophage tissue factors, which are considered as physiological initiator of coagulation [2] .Ovarian cancer lesion resection and lymph node dissection cause severe trauma to human tissues, resulting in vascular endothelial injury and coagulation factor leakage, resulting in cytokine release and activation of exogenous coagulation pathway [9] .The long operation time and postoperative bed rest lead to a long time of immobility of the limbs, the decline of the lower limb muscle pump function, slow blood ow and even stagnation, and then lead to thrombosis.In the literature, more than 100 minutes of operation time was associated with an increased risk of DVT (OR=1.30, 95%CI: 1.12-2.21) and PE (OR=1.25,, each additional 10 minutes after 100 minutes increased the risk of DVT by 7%, while the risk of PE increased by 5% [10] .In addition, most studies have pointed out that the recovery of minimally invasive surgery is faster, the patients move to the ground earlier, and some risk factors for THE formation of VTE are avoided, thus the risk of VTE is lower than that of open surgery.However, some other scholars believe that the risk of thrombosis is increased due to the long time of minimally invasive gynecological surgery, the pressure of lower limb veins subjected to pneumoperitoneum, blocked blood return, and the increased operation time caused by laparoscopy or robotic surgery [11] .In fact as long as patients surgery, and surgery related factors on the impact of thrombosis occurs cannot be avoided, but you can try to reduce risks in other way, such as operation skills, choose a suitable operation method, etc., at the same time improve the high-risk group recognition, to ensure more reasonable and normative thromboembolism prophylaxis.…”

Сonsensus statement of Russian experts on the prevention, diagnosis and treatment of cardiotoxicity of anticancer therapy

“…Хорошо известные механизмы, способствующие развитию тромботических осложнений, такие как венозный застой, эндотелиальная дисфункция, ведущая к потере антитромботических свойств, и гиперкоагуляция (триада Вирхова), при ОЗ реализуются через специфические влияния злокачественных клеток растущей опухоли на организм. Основными способами взаимодействия опухолевой клетки с системой гемостаза является выработка особых молекул, обладающих прокоагулянтной и фибринолитической активностью, таких как тканевой фактор и раковый прокоагулянт, продукция провоспалительных цитокинов, что нарушает регулирующее действие эндотелия, снижает синтез естественных антикоагулянтов (протеина С и антитромбина III) [390,391].…”