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Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment.

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    By Katherine Kozlowski, Associate Editor of Vein News VeinsVeinsVeins.com

    Venous thromboembolism is a major cause of mortality in patients with cancer.

    Venous thromboembolism includes deep vein thrombosis (a clot in the lower extremity) and pulmonary embolism (when a clot from a deep vein travels to the lungs). This can result in partial or total loss of blood flow to the lungs, and death if not treated immediately.

    Cancer patients have several risk factors for developing VTE. These include chemotherapy, long periods of immobilization, and cancer cells activating the coagulation cascade and pro-thrombotic properties of normal body cells.

    The following risk factors are discussed below:
    • Age: As humans age, there is a much higher incidence rate of VTE. This association also exists in patients with cancer.
    • Comorbidities: Renal failure, lung diseases, heart disease, obesity, and infection have all been associated with an increased risk of VTE in cancer patients.
    • Immobility: Higher rates of VTE were found in cancer patients who were sedentary than those who were more active. Additionally, Bed rest of more than 3 days is associated with an increased risk of VTE. This is due to the pooling of blood in the veins, which does not allow for proper blood flow from the lower limbs to the heart.
    • Site of Cancer: Cancer of the uterus, lung, stomach, kidney, and primary brain tumors (starting in the brain) are associated with an increased risk of VTE.
    • Cancer Stage: According to several studies, late-stage cancer patients were more likely to develop VTE.
    • Surgery and Hospitalization: VTE is a complication after surgery due to bed rest, and patients who underwent cancer surgery had 2x the risk of developing DVT and 3x the risk of developing fatal PE compared to patients who did not have cancer surgeries.
    • Chemotherapy: Cancer patients undergoing chemotherapy have a 6-7x increased chance of developing VTE.
    • Central Lines: Central Lines are often placed for chemotherapy administration; however, they increase the risk of developing catheter-related thrombosis.
    What are the Direct Mechanisms for Cancer-Associated Thrombosis?
    • According to 68, Tissue Factor (TF) is a procoagulant protein that is derived from tumors. These initiate the “coagulation cascade” which is a series of events eventually leading to increased platelet count and blood clotting.
    • Microparticles, which are small parts of a cell that can come off of tumor cells or dying cells, can express Tissue Factor causing an increased risk of blood clotting through the coagulation cascade.
    • There are several other proteins, particles, and cytokines released from cancer or cancer-associated cells that can cause the body of a patient with cancer to be in a hypercoagulable state.
    • Tumors can cause small environments lacking oxygen that can lead to dysfunction of cells causing them to stimulate the production of more platelets (blood-clotting cells).
    • Chemotherapy can cause toxicity of liver cells, which leads to decreased levels of ANTI-coagulant proteins (protein S, protein C, and antithrombin).
    How can you address the cancer-associated risk of VTE?

    Patients who have cancer and are undergoing chemotherapy, surgery, or any other risk factors should be using VTE prophylaxis, periodic assessment for VTE, and learn the signs and symptoms of VTE. Further research is also warranted.

    Reference: Razak A, Jones G, Bhandari M et al. Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment. Cancers 2018; 10(10): 380.