Blood clots, or thrombosis, occur when blood components solidify into a gel-like mass inside a blood vessel, usually as a protective mechanism to stop bleeding following an injury. The frequent co-occurrence of thrombosis and cancer has been noted by physicians for over a century, pointing to a complex biological relationship between an abnormal clotting tendency and malignancy.
The Established Connection Between Blood Clots and Cancer
The association between cancer and an increased risk of developing blood clots is known as Cancer-Associated Thrombosis (CAT). This is a significant complication, as the prevalence of venous thromboembolism (VTE) can be up to twelve times higher in cancer patients than in the general population. VTE is the second leading cause of death in cancer patients after disease progression.
The connection is bidirectional: cancer increases clotting risk, and an unexplained clot can signal an underlying malignancy. This presentation, where a clot precedes a cancer diagnosis, is sometimes called Trousseau Syndrome. For those experiencing an unprovoked clot—without factors like recent surgery or prolonged immobility—approximately 10% will be diagnosed with cancer within the following year.
How Malignancy Triggers Clot Formation
The biological explanation for why cancer cells promote clotting relates to the concept of hypercoagulability, meaning the blood has an increased tendency to clot. This hypercoagulable state is driven by multiple factors, primarily involving the tumor cells directly interacting with the body’s coagulation system.
Tissue Factor Release
A primary mechanism involves the release of pro-coagulant substances, most notably a protein called Tissue Factor (TF). While TF typically initiates clotting only after vessel injury, cancer cells often abnormally express this protein and shed it into the bloodstream attached to microvesicles. This circulating TF activates the coagulation cascade systemically, leading to the rapid generation of thrombin and the formation of fibrin clots in distant vessels.
Systemic Inflammation
Tumors also cause systemic inflammation throughout the body. This inflammation triggers the release of signaling molecules, called cytokines, that damage the inner lining of blood vessels (the endothelium). Endothelial damage is a component of Virchow’s Triad, providing an ideal surface for clot formation.
Blood Flow Stasis
A third mechanism involves the physical presence of the tumor mass, particularly in advanced stages. Large tumors can physically compress nearby blood vessels, slowing the flow of blood through them. This slowed blood flow, or stasis, is another element of Virchow’s Triad, allowing clotting factors and platelets to accumulate and increasing the likelihood of clot formation.
High-Risk Cancers and Specific Clot Types
The risk of thrombosis varies substantially depending on the type and location of the malignancy. The highest rates are seen in patients with adenocarcinomas, particularly cancers of the pancreas, stomach, and ovaries. Other high-risk cancers include those affecting the brain, lung, kidney, and blood cancers like lymphoma and myeloma.
The majority of clots associated with malignancy are Venous Thromboembolism (VTE), consisting of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). DVT is a clot, usually in the deep veins of the legs or pelvis, causing pain and swelling. PE occurs when a piece of the DVT travels to the lungs, potentially causing shortness of breath and chest pain.
The risk is compounded by cancer treatment, as chemotherapy, hormonal therapies, and central venous catheters can all increase the chances of a thrombotic event. Common cancers like breast, prostate, and colorectal malignancies also contribute significantly to VTE cases due to their high prevalence.
When a Blood Clot Warrants Further Cancer Screening
Investigating a blood clot for underlying malignancy depends on whether the clot is “provoked” or “unprovoked.” A provoked clot has a clear, temporary cause, such as recent major surgery or prolonged immobilization. An unprovoked clot occurs spontaneously without an obvious transient risk factor, raising suspicion for a hidden condition like cancer.
Medical guidelines recommend a limited screening approach for patients presenting with a first unprovoked VTE. This includes a detailed medical history and physical examination, basic laboratory tests (complete blood count and liver function tests), and a chest X-ray. Age- and gender-specific cancer screenings, such as colonoscopies or mammograms, are also recommended if they are overdue.
Routine CT scans of the abdomen and pelvis are not recommended for every patient with an unprovoked clot. Studies have not shown that extensive screening improves overall survival compared to a limited approach, and it carries risks like increased cost, patient anxiety, and unnecessary invasive procedures. Patients with specific signs, such as unexpected weight loss, anemia, or an unusual location for the clot (e.g., an upper extremity DVT), may warrant a more thorough investigation.