Blood clots in the leg, known as deep vein thrombosis (DVT), form when blood flow slows down, a vein wall is damaged, or the blood itself becomes more prone to clotting. Up to 900,000 people in the United States are affected by blood clots each year, and an estimated 60,000 to 100,000 die from complications. Understanding what triggers these clots can help you recognize whether you’re at higher risk.
The Three Conditions That Lead to a Clot
Every leg clot traces back to one or more of three overlapping problems. The first is slow or stagnant blood flow. Veins in the legs rely on muscle contractions and one-way valves to push blood back toward the heart. When blood pools, especially in the small pockets near those valves, it has time to thicken and form a clot. The second is damage to the inner lining of a vein. A healthy vein wall actively prevents clotting by releasing protective molecules like nitric oxide and prostacyclin. When that lining is injured by trauma, surgery, or inflammation, the protective barrier breaks down and the blood shifts toward clot formation. The third is a change in the blood itself that makes it clot too easily, whether from genetics, medications, or an underlying disease.
Most people who develop a leg clot have at least two of these factors working together. Surgery, for example, combines vein damage from the procedure with prolonged bed rest afterward. Pregnancy raises clotting factor levels while also compressing veins. These overlapping triggers explain why clots often appear during specific life events rather than out of nowhere.
Surgery and Hospitalization
Major surgery is one of the strongest triggers for leg clots. Orthopedic procedures carry especially high risk because they involve direct manipulation of bones and tissues near large veins. Studies report DVT rates of 18% to 49% after total knee replacement and 18% to 24% after total hip replacement when preventive measures aren’t used. Even with modern prevention protocols, the rates still reach roughly 13% for knee surgery and 5% for hip surgery.
It’s not just orthopedic operations. Any surgery that keeps you immobile for hours, particularly abdominal, pelvic, or cancer-related procedures, raises your risk. Hospital stays in general are a major factor because they combine bed rest, possible vein catheter insertion, and the inflammatory response your body mounts after illness or injury.
Prolonged Sitting and Travel
You don’t need to be hospitalized for blood flow to slow dangerously. Sitting for long stretches, whether on a plane, in a car, or at a desk, reduces the muscle contractions in your calves that normally squeeze blood upward through leg veins. The CDC notes that anyone traveling more than four hours by air, car, bus, or train faces increased clot risk. The threshold isn’t about altitude or cabin pressure specifically. It’s about time spent sitting still with your legs bent.
The same logic applies to people with sedentary jobs or anyone recovering from an injury that limits leg movement. Paralysis, a leg cast, or even a long stretch of bed rest after an illness can create enough stagnation for a clot to form.
Inherited Clotting Disorders
Some people are born with blood that clots more readily than normal. The most common inherited condition is a gene mutation called Factor V Leiden, found in about 1% to 5% of white populations. Carrying one copy of this mutation increases your lifetime clot risk roughly sevenfold. Carrying two copies, which is rare, increases it about twentyfold. Among people who have already had a blood clot, 10% to 20% turn out to carry this mutation.
Other inherited conditions that raise clotting risk include the prothrombin gene mutation and deficiencies in natural anticoagulant proteins your body produces. Many people with these conditions go their entire lives without a clot, but when a second trigger appears, like surgery, pregnancy, or a long flight, the combination can tip the balance. If you’ve had an unexplained clot, especially before age 50, or if blood clots run in your family, genetic testing can reveal whether an inherited condition played a role.
Cancer
Cancer and blood clots are closely linked. Tumors can release substances that activate the clotting system, and cancer treatments like chemotherapy further raise the risk. Some cancers are more strongly associated with clots than others. Cancers of the pancreas, stomach, brain, lungs, uterus, ovaries, and kidneys pose the greatest risk. Blood cancers such as lymphoma and myeloma also increase clot likelihood. In some cases, an unexplained blood clot is actually the first sign that leads to a cancer diagnosis.
Hormones and Birth Control
Estrogen increases the levels of several clotting factors in the blood. Combined oral contraceptives (those containing both estrogen and a progestin) raise the risk of venous blood clots about 3.5-fold compared to non-use, according to a large systematic review published in The BMJ. That sounds alarming in relative terms, but the baseline risk for young, healthy women is very low, so the absolute risk remains small for most users. Still, the risk climbs when birth control is combined with other factors like smoking, obesity, or a genetic clotting disorder.
Hormone replacement therapy containing estrogen carries a similar increase in clot risk, particularly oral forms. Estrogen delivered through skin patches appears to carry less risk than pills, likely because it bypasses the liver where clotting factors are produced.
Pregnancy and Postpartum
Pregnancy creates a perfect storm for clot formation. Hormone levels surge, blood volume increases, and the growing uterus compresses the veins that return blood from the legs. The blood itself becomes more “clottable” as the body prepares for the bleeding that comes with delivery.
The risk doesn’t end at birth. Research shows that clot risk stays significantly elevated for at least 12 weeks after delivery. In exploratory analyses, risk remained increased through about 15 weeks postpartum before returning to normal around week 16. This means the traditional six-week postpartum checkup doesn’t mark the end of the high-risk window.
Obesity
Carrying excess weight increases clot risk through several pathways. Extra body mass compresses veins in the pelvis and legs, slowing blood flow. Obesity is also associated with higher levels of clotting factors circulating in the blood. The risk rises with increasing BMI: a BMI of 30 or above (the threshold for obesity) is an established DVT risk factor, and the risk continues climbing through higher weight categories. People with a BMI of 40 or above face the greatest risk. The combination of obesity with another trigger, like surgery or a long flight, multiplies the danger considerably.
Other Medical Conditions
Several chronic conditions independently raise clot risk. Heart failure slows overall circulation, allowing blood to pool. Inflammatory bowel diseases like Crohn’s and ulcerative colitis create a systemic inflammatory state that promotes clotting. Severe infections, including COVID-19, can damage blood vessel walls and activate the clotting cascade. Kidney disease, particularly nephrotic syndrome, causes the body to lose natural anticoagulant proteins through the urine.
A previous DVT is itself a major risk factor. Once you’ve had one clot, the affected vein may be permanently narrowed or the valves damaged, making a second clot in the same area more likely.
Age
DVT can happen at any age, but the risk rises sharply after 40 and continues increasing with each decade. Older adults are more likely to have multiple risk factors stacking up at once: reduced mobility, chronic illness, medications, and natural changes in blood vessel walls that accumulate over a lifetime. The combination matters more than any single factor, which is why clots most commonly appear in older adults dealing with illness or recovering from surgery.
Why Multiple Risk Factors Matter Most
In practice, isolated risk factors rarely cause clots on their own. A healthy 30-year-old on a long flight will almost certainly be fine. But a 30-year-old on birth control who also carries Factor V Leiden and sits for six hours on a plane faces meaningfully higher risk. The causes listed above interact and amplify each other, which is why the most dangerous moments tend to cluster around life events that stack multiple triggers: a major surgery in an older patient with cancer, or a postpartum woman with a family history of clotting disorders who is bedridden after a cesarean delivery.
Recognizing which factors apply to you helps you and your medical team decide when preventive steps, like compression stockings, blood-thinning medication during a hospital stay, or simply making a point to move your legs on a long trip, are worth taking.