Deep vein thrombosis (DVT) happens when a blood clot forms in one of the body’s deep veins, usually in the legs. Three underlying conditions drive clot formation: slow blood flow, damage to the blood vessel wall, and blood that clots too easily. Most cases of DVT involve at least two of these factors occurring at the same time, which is why risk rises sharply when multiple triggers overlap.
The Three Conditions Behind Every Clot
In 1856, a physician named Rudolf Virchow identified the three biological conditions that lead to blood clots in veins. These remain the framework doctors use today.
Sluggish blood flow is the most important of the three. Blood naturally pools in areas where flow slows down, particularly around the tiny valves inside leg veins. These valves normally keep blood moving upward toward the heart, but they also create small pockets where blood can stagnate. When flow slows, oxygen levels in that pooled blood drop and the concentration of clotting cells rises. Stasis alone doesn’t usually cause a clot, but it sets the stage.
Blood vessel damage provides the spark. When the inner lining of a vein is injured, the body releases a protein called tissue factor that kicks off the clotting process. Surgery, trauma, infection, or even the insertion of a catheter can cause this kind of damage. The injured vessel wall becomes sticky, attracting platelets and clotting proteins to the site.
Blood that clots too easily tips the balance. Your blood contains both proteins that promote clotting and proteins that prevent it. When the ratio shifts toward clotting, whether from genetics, hormones, cancer, or inflammation, clots form more readily. In large veins, the ratio naturally favors clotting proteins, which is one reason DVT tends to strike in the deep veins of the legs and pelvis rather than smaller vessels.
Immobility and Long Periods of Sitting
Anything that keeps your legs still for extended periods slows blood return from the lower body. The calf muscles act as a pump for venous blood, so when you’re not moving them, blood pools. This is why DVT risk climbs during long flights, car rides, or train journeys lasting more than four hours. The risk applies regardless of the mode of transportation.
Bed rest creates similar conditions. Being confined to bed for more than three days, whether from illness, injury, or recovery from surgery, is one of the most common DVT triggers. A leg cast or brace that prevents normal movement has the same effect, immobilizing the muscle pump and letting blood sit in the deep veins.
Surgery, Especially Orthopedic Procedures
Major surgery is one of the strongest risk factors for DVT because it can trigger all three clotting conditions at once. The procedure damages blood vessels, the patient is immobilized during and after the operation, and the body’s inflammatory response shifts blood chemistry toward clotting.
Orthopedic surgeries carry particularly high risk. Without preventive measures like blood thinners or compression devices, DVT rates after major joint replacement or hip fracture repair can reach 40 to 60 percent. That number drops dramatically with modern prevention protocols, but surgery on the lower body remains a significant trigger. General abdominal and pelvic surgeries also raise risk, though typically to a lesser degree.
Cancer and Blood Clot Risk
Cancer increases DVT risk through several overlapping mechanisms. Tumor cells directly produce tissue factor, the same protein that normally triggers clotting at wound sites. They also release tiny particles called extracellular vesicles that carry tissue factor into the bloodstream, promoting clot formation far from the tumor itself.
Beyond that, cancer disrupts the body’s natural clot-dissolving system. Tumors increase production of a protein that blocks the enzymes responsible for breaking down clots, allowing fibrin (the structural material of a clot) to accumulate. Cancer cells also secrete chemicals that activate platelets and inflame blood vessel walls, creating an environment where clots form more easily and persist longer. Inflammatory signals from the tumor recruit immune cells that release web-like structures of DNA, which act as scaffolding for platelets and clotting proteins to build on.
Certain cancers carry higher DVT risk than others, particularly cancers of the pancreas, brain, lung, ovary, and stomach. Chemotherapy can further increase the risk by damaging blood vessel linings and altering clotting protein levels.
Hormones: Pregnancy and Contraceptives
Pregnancy raises DVT risk in multiple ways. The body increases its clotting ability during pregnancy to protect against excessive bleeding during delivery. At the same time, the growing uterus presses on pelvic blood vessels, reducing blood flow from the legs. Women are at elevated risk throughout pregnancy and for three months after delivery, with the postpartum period being particularly dangerous as the body recovers from the physical stress of childbirth.
Combined oral contraceptives (those containing both estrogen and a progestin) increase DVT risk roughly 3.5 times compared to non-use. The risk varies slightly by formulation: older second-generation pills raise risk about 2.8-fold, while newer third-generation versions increase it about 3.8-fold. To put this in perspective, the baseline risk for the general population is about 1 in 1,000 people per year. For most young, healthy women on the pill, the absolute risk remains low, but it becomes more meaningful when combined with other factors like smoking, obesity, or an inherited clotting disorder.
Hormone replacement therapy used during menopause carries a similar increase in clotting risk, particularly oral forms that pass through the liver.
Inherited Clotting Disorders
Some people are born with blood that clots more readily than normal. The most common inherited clotting condition is Factor V Leiden, a genetic mutation that makes one of the blood’s clotting proteins resistant to being switched off. Carrying one copy of this mutation raises your annual DVT risk from about 1 in 1,000 to 3 to 8 in 1,000. Carrying two copies (one from each parent) pushes the risk as high as 80 in 1,000, a dramatic increase.
Other inherited conditions include mutations in the prothrombin gene, deficiencies in natural anticoagulant proteins like protein C or protein S, and elevated levels of certain clotting factors. Many people with these conditions never develop a clot on their own, but when a second trigger appears, like surgery, pregnancy, or a long flight, the combination can be enough to tip the balance.
An Anatomical Cause: May-Thurner Syndrome
In some people, the anatomy itself creates a problem. May-Thurner syndrome occurs when the right iliac artery (which carries blood to the right leg) crosses over and compresses the left iliac vein beneath it. This compression slows blood flow through the left leg and can damage the vein wall over time.
The condition helps explain why DVT occurs more often in the left leg than the right. In studies of patients with left-sided clots in the upper leg and pelvic veins, roughly 70 to 75 percent had evidence of this compression. Many people have some degree of compression without ever developing symptoms, but it becomes clinically significant when combined with other risk factors.
Other Contributing Factors
Obesity increases DVT risk by raising pressure in the pelvic and leg veins, slowing blood return, and promoting a chronic low-grade inflammatory state that shifts blood chemistry toward clotting. The risk rises progressively with increasing body weight.
Age plays a significant role. DVT is rare in children and young adults but becomes increasingly common after age 40, with risk roughly doubling each decade after that. Older adults are more likely to have multiple overlapping risk factors: reduced mobility, chronic illness, and age-related changes in blood vessel walls and clotting protein levels.
Smoking damages blood vessel linings and makes platelets stickier, contributing to both arterial and venous clots. A previous DVT is itself a strong risk factor for another one, as the original clot often damages vein valves and creates areas of turbulent flow that are prone to re-clotting. Inflammatory conditions like lupus, inflammatory bowel disease, and certain kidney disorders also shift the clotting balance.
Why Risk Factors Often Stack
The key principle with DVT is that risk factors are multiplicative, not just additive. A woman with Factor V Leiden who starts oral contraceptives faces a much higher combined risk than either factor alone would suggest. A cancer patient who undergoes surgery and is then immobilized in bed is exposed to all three of Virchow’s original triggers simultaneously.
This stacking effect is why doctors assess DVT risk before surgery, during hospital stays, and when prescribing hormonal medications. It also explains why DVT can occasionally strike people who seem healthy: they may carry an undiagnosed genetic predisposition that only becomes apparent when a second trigger, like a long flight or a minor injury, is added.