Cancer significantly elevates a person’s risk of developing blood clots, a serious complication commonly referred to as Cancer-Associated Thrombosis (CAT). This link between malignancy and clotting, first observed over a century ago as Trousseau syndrome, immediately puts a patient into a hypercoagulable state. Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, stands as the second leading cause of death in cancer patients, second only to the cancer itself.
The Mechanism Behind Clot Formation
Cancer creates an environment that promotes clot formation by disrupting the normal balance of blood clotting and breakdown. This pro-thrombotic state involves all three components of Virchow’s Triad: changes to the blood vessel wall, alterations in blood flow, and increased coagulability of the blood.
A primary molecular driver is the release of pro-coagulant factors directly from tumor cells. Malignant cells often express high levels of Tissue Factor (TF), which acts as the main trigger for the extrinsic coagulation cascade. When TF interacts with the blood, it rapidly initiates the generation of thrombin and the formation of fibrin, the structural meshwork of a clot.
Cancer also induces systemic inflammation, further activating the clotting process. Tumor cells and surrounding immune cells secrete inflammatory signaling molecules, such as cytokines. These cytokines act on the lining of blood vessels (the endothelium), causing these cells to become sticky and express pro-coagulant proteins.
Cancer treatments can also contribute to clotting risk by causing direct injury to blood vessel walls. Chemotherapy and certain targeted drugs may damage the endothelial lining, exposing underlying tissue that triggers platelet adhesion. Furthermore, immobility and prolonged hospitalization associated with cancer treatment lead to blood flow stasis, allowing clots to form more easily, particularly in the lower extremities.
Identifying High-Risk Cancers and Patients
The risk of developing a clot is not uniform across all malignancies and is heavily influenced by the specific type and stage of cancer. Cancers of the pancreas, stomach, and brain are consistently associated with the highest rates of thrombosis. Other high-risk solid tumors include those affecting the lung, kidney, and gynecological organs.
Hematological malignancies, such as lymphomas and multiple myeloma, also carry a significant risk of thrombosis. The risk is greater in patients with advanced-stage or metastatic disease, where the tumor burden is higher and more pro-coagulant material is circulating.
Clinical factors separate from tumor biology also influence a patient’s susceptibility to clots.
- Immobility
- Obesity (BMI greater than 35)
- Presence of a central venous catheter or PICC line
- High platelet count
- Elevated white blood cell count
Oncologists use risk assessment tools, such as the Khorana Risk Score (KRS), to identify patients who would benefit most from preventative medication. The KRS assigns points based on the site of cancer, blood counts (platelet, white cell, and hemoglobin levels), and Body Mass Index. Patients with a score of two or higher are classified as intermediate or high risk, indicating a potential need for primary prophylaxis.
Recognizing Symptoms of Thrombosis
Patients and caregivers must recognize the distinct symptoms of the two most common forms of VTE. Deep Vein Thrombosis (DVT) is the formation of a clot, usually in a deep vein of the leg or occasionally the arm.
Symptoms of a DVT include swelling, pain, or tenderness in the affected limb, often in the calf or thigh. The skin over the area may feel warm to the touch and appear red or discolored. Immediate medical evaluation is required if a patient experiences these signs, as a DVT can break off and travel elsewhere in the body.
When a piece of the DVT travels through the bloodstream to the lungs, it causes a Pulmonary Embolism (PE). Symptoms of a PE are acute and involve the respiratory and circulatory systems.
A sudden onset of shortness of breath or difficulty breathing is a common presentation of PE. Patients may experience sharp chest pain that worsens when taking a deep breath or coughing. Other symptoms include a rapid or irregular heartbeat, and coughing up blood in severe cases.
Treating and Preventing Cancer-Associated Clots
Management of a diagnosed cancer-associated clot requires anticoagulant medications, commonly known as blood thinners. The goal is to stop the existing clot from growing larger and prevent new clots from forming.
Low Molecular Weight Heparin (LMWH), administered via injection, was long the standard of care for treating CAT and remains an effective option. However, Direct Oral Anticoagulants (DOACs) are now frequently used as an alternative. DOACs are more convenient because they are taken as pills and have been shown to be superior to LMWH in reducing the risk of clot recurrence in many cancer types.
The choice between LMWH and a DOAC depends on the patient’s specific cancer type and bleeding risk, as certain DOACs are associated with a greater risk of major bleeding in patients with gastrointestinal cancers. Treatment for CAT is typically extended for a minimum of six months, which is longer than the duration required for non-cancer patients.
Prevention, or primary prophylaxis, involves administering anticoagulants to high-risk patients who have not yet developed a clot. Guidelines recommend preventative medication for hospitalized cancer patients and for high-risk ambulatory patients receiving chemotherapy, often identified by risk scores like the KRS. Prophylaxis significantly reduces the incidence of VTE, but the decision to start is carefully weighed against the potential for increased bleeding.