Thrombotic events are the second-leading cause of death in patients with cancer after the disease itself. An estimated 4%–20% of patients experience venous thromboembolism at some stage on the cancer journey.
Risk Factors
Risk factors for cancer-related thrombosis include chemotherapy, immobilization, use of venous access devices, and activation of the coagulation cascade. A systematic review and meta-analysis reported that pancreatic cancer displayed the highest risk of venous thromboembolism.
Chemotherapy agents that are known to be prothrombotic include platinum-based therapies, VEGF inhibitors (bevacizumab), and VEGF tyrosine kinase receptor inhibitors (sorafenib, sunitinib, pazopanib). Other risk factors include age older than 85 and comorbid conditions such as renal failure, respiratory disease, heart disease, obesity, or acute infection.
Complications
Disseminated intravascular coagulation affects 7% of patients with solid tumors and 15%–20% of patients with liquid tumors, particularly acute leukemia. It’s characterized by widespread activation of the coagulation cascade with simultaneous consumption of coagulation factors and platelets, which results in bleeding. Treatment involves managing the underlying problem. Supportive therapy may include anticoagulation, with unfractionated or low-molecular weight heparin as the standard of care.
Deep vein thrombosis and pulmonary embolism are frequently seen in at-risk patients with cancer and should be considered as diagnoses when patients present with symptoms consistent with those conditions. For thrombosis, the primary treatment is anticoagulation. In general, in patients with a malignancy and venous thromboembolism but without renal insufficiency, low-molecular weight heparin remains the preferred agent. Dosing for low-molecular weight heparins will vary based on the drug selected, and dose reductions are required for creatinine clearance less than 30 ml per minute.
Management
Some providers treat venous thromboembolism with the direct oral anticoagulants apixaban or rivaroxaban, although data for their use in cancer is somewhat limited. The National Comprehensive Cancer Network guidelines suggest that apixaban or rivaroxaban are reasonable alternatives to low-molecular weight heparin. Warfarin can be considered for some patients with doses of 2.5–5 mg for an international normalized ratio goal of 2–3. Drug interactions need to be considered. When deciding on an appropriate anticoagulant, drug interactions, prescription coverage, and a patient’s ability to safely administer self-injections must be considered.
Close monitoring is essential for patients on anticoagulation; patients with metastatic disease may require lifelong therapy and ongoing lab monitoring, especially renal function, liver function, and platelet counts. Thrombocytopenia increases the risk of bleeding in this setting.