From the Guidelines
Cancer promotes thrombosis through multiple mechanisms, including the release of tissue factor and cancer procoagulant, which directly activate the coagulation cascade, as well as systemic inflammation and damage to blood vessel walls, leading to increased levels of inflammatory cytokines and platelet aggregation, as described in the most recent guidelines by the European Society for Medical Oncology 1. The mechanism of thrombosis in cancer is complex and multifactorial, involving various cancer-related and patient-related factors. Some key factors that contribute to thrombosis in cancer patients include:
- Tumor cells releasing procoagulant proteins, such as tissue factor and cancer procoagulant, which activate the coagulation cascade
- Systemic inflammation, leading to increased levels of inflammatory cytokines that damage blood vessel walls and promote platelet aggregation
- Tumors compressing blood vessels, causing blood stasis and increasing clot risk
- Cancer treatments, such as chemotherapy, hormonal therapy, and surgery, which can damage vessel walls and increase procoagulant factors
- Patient-related factors, such as immobility, central venous catheters, and comorbidities, which can compound the thrombotic risk. According to the most recent guidelines, certain cancers, particularly pancreatic, stomach, and primary brain tumors, pose a higher risk of thrombosis due to the release of specific procoagulant proteins, such as tissue factor and podoplanin 1. Understanding these mechanisms is crucial for appropriate prophylaxis and treatment, which may include low molecular weight heparin, direct oral anticoagulants, or mechanical methods, depending on the patient's specific cancer type, stage, and treatment regimen, as recommended by the American Society of Hematology 1 and the European Society for Medical Oncology 1.
From the Research
Mechanisms of Thrombosis in Cancer
The mechanism of thrombosis in cancer is complex and involves both clinical and biological factors. Some of the key mechanisms include:
- Tumor cells activating the coagulation system by producing and secreting procoagulant/fibrinolytic substances and inflammatory cytokines 2
- Physical interaction between tumor cells and blood cells (monocytes, platelets, neutrophils) or vascular cells 2
- Generation of acute phase reactants and necrosis (i.e., inflammation) 2
- Abnormal protein metabolism (i.e., paraproteinemia) 2
- Hemodynamic compromise (i.e., stasis) 2
- Anticancer therapy (i.e., surgery/chemotherapy/hormone therapy) increasing the risk of thromboembolic events 2, 3
Clinical and Biological Risk Factors
The risk of thrombosis in cancer patients varies according to the type of malignancy and its disease stage, and is increased by concomitant patient-related thrombotic risk factors (i.e. advanced age, infection, heart disease) 4. Tumor cell-specific prothrombotic properties and the host cell inflammatory response also contribute to the risk of thrombosis in these patients 4.
Pathogenesis of Blood Hypercoagulability
The pathogenesis of blood hypercoagulability in cancer patients involves various factors, including:
- Tumor cells releasing coagulant-promoting substances 5
- Tumor cells interacting with the fibrinolytic system 5
- Tumor cell-mediated platelet activation 5
- Tumor-associated complement activation 5
- Genetic factors and clinical factors 5
Interplay between Cancer and Blood Coagulation
The interplay between cancer and blood coagulation is complex, with blood coagulation proteins interacting with cells in the vasculature to maintain hemostasis, and also being involved in cell-signaling mechanisms in extravascular tissues 6. The potential procarcinogenic actions of proteases like thrombin may be counteracted by the anticoagulant and anti-inflammatory actions of the protein C-thrombomodulin mechanism 6.