The development of blood clots (thrombosis) is a frequent and serious complication for individuals with cancer, often termed Cancer-Associated Thrombosis (CAT) or Trousseau’s Syndrome. Individuals with cancer face a risk of developing venous thromboembolism (VTE) that is five to seven times higher than the general population, making it a leading cause of death in this patient group. This heightened risk results from a complex interplay of factors involving the tumor, the body’s response to the malignancy, and necessary treatments.
The Hypercoagulable State
Cancer creates a systemic environment where the blood is constantly poised to clot, known as hypercoagulability. This shift is described using Virchow’s triad: changes in blood flow, damage to the vessel wall, and alterations in blood composition. Cancer contributes to all three factors, tipping the balance toward clot formation.
The presence of a tumor can physically compress nearby blood vessels, particularly veins, leading to a slowing or pooling of blood (stasis). This obstruction encourages blood components to aggregate, initiating clotting. Furthermore, cancer drives a low-grade, chronic inflammatory state that influences blood components and inadvertently contributes to the pro-clotting environment.
Tumor Cell Procoagulants
Cancer cells directly promote clotting by releasing specific molecules that trigger the coagulation cascade. The most well-studied is Tissue Factor (TF), a protein that functions as the primary initiator of clotting upon injury. Tumor cells express high levels of TF and shed it into the bloodstream on tiny membrane fragments called microparticles.
When TF-bearing microparticles circulate, they bind to Factor VIIa, activating the extrinsic pathway of coagulation. This rapidly leads to the production of thrombin, which converts fibrinogen into fibrin, forming a stable clot. The amount of TF expression correlates with the tumor’s aggressiveness and the patient’s thrombosis risk. Another procoagulant protein, Cancer Procoagulant, also contributes to this activation.
Inflammation and Endothelial Dysfunction
Systemic inflammation associated with cancer is a powerful driver of thrombosis because it damages the inner lining of blood vessels, known as the endothelium. Healthy endothelial cells normally prevent clotting by acting as a smooth surface and releasing molecules that inhibit platelet aggregation.
In the presence of a tumor, the body releases inflammatory signaling molecules, such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α). These cytokines damage the endothelium, causing cells to become dysfunctional and shift to a pro-clotting state. Damaged endothelial cells express adhesion molecules and pro-thrombotic factors, promoting the attachment of platelets and clotting proteins.
Platelet Activation and Aggregation
Platelets, the small blood cells responsible for initial clot formation, are heavily influenced by cancer. Cancer cells and their shed microparticles directly activate platelets, making them stickier and more prone to aggregation. Activated platelets then release growth factors and pro-clotting substances, further amplifying the coagulation cascade.
The interaction between tumor cells and platelets is a complex process that benefits the cancer. Platelets can coat circulating tumor cells with a layer of fibrin, shielding them from immune detection. This coating facilitates metastasis by allowing tumor cells to become trapped in small blood vessels in distant organs.
Treatment-Related Risk Factors
Many common cancer treatments independently raise the risk of developing blood clots, beyond the biological effects of the malignancy. Certain chemotherapy agents are prothrombotic, either by damaging the endothelial lining or altering clotting proteins; platinum-based drugs like cisplatin are examples. Hormonal therapies, such as tamoxifen used for breast or prostate cancer, also increase VTE risk. Supportive care measures, like central venous catheters, can injure the vessel wall and initiate localized clots. Immobility following surgery or during long hospital stays further slows blood flow, contributing to thrombotic risk.
Cancer Type and Clotting Risk
The risk of thrombosis is not uniform across all cancer types; it varies significantly depending on the tumor site and stage. Cancers of the pancreas, stomach, and brain are consistently associated with the highest rates of VTE, with pancreatic cancer having one of the highest incidences.
Other cancers, including those of the lung, ovary, and kidney, also carry a substantially increased risk. This variation relates to the differing amounts of procoagulant factors, such as Tissue Factor, released by specific tumor types. The risk also rises with the stage of the disease, with metastatic cancer patients being at the highest risk for clot formation.
Anticoagulation Strategies
Managing and preventing thrombosis is an important part of cancer care due to the high risk and serious consequences of blood clots. All cancer patients are periodically assessed for VTE risk, and preventative measures are implemented for those deemed high-risk. Low molecular weight heparin (LMWH) has historically been the preferred treatment for established cancer-associated VTE because it prevents clot recurrence effectively.
More recently, direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, have shown comparable efficacy in preventing VTE recurrence in many cancer patients. The choice of anticoagulant requires careful consideration, balancing the risk of new clot formation against the increased risk of major bleeding. Specific factors, including cancer type, platelet count, and potential drug interactions with chemotherapy, influence the final treatment decision.