A thromboembolic event happens when a blood clot forms inside a vessel and either blocks flow at that spot or breaks loose and travels to block a vessel somewhere else. The underlying causes fall into three broad categories that physicians have recognized for over a century: sluggish or stagnant blood flow, damage to the vessel lining, and blood that clots too easily. In practice, most thromboembolic events involve more than one of these triggers working together, which is why the list of risk factors is so long and why prevention has to address multiple angles at once.
How Clots Form Where They Should Not
Your blood is constantly balancing two opposing jobs. It needs to clot fast enough to seal a wound, but it also needs to stay liquid enough to flow freely through tens of thousands of miles of blood vessels. A thromboembolic event is what happens when that balance tips too far toward clotting. Both inherited traits and acquired conditions can push the balance in that direction through increased blood coagulability, damage to the inner vessel wall, or circulatory stasis.1PubMed Central. A Comprehensive Review of Risk Factors and Thrombophilia Evaluation in Venous Thromboembolism
In veins, clots tend to start in spots where blood pools, especially the valve pockets of deep leg veins. These small pockets can become low in oxygen when blood sits too long without moving. That oxygen-starved environment activates the vessel lining, which starts displaying sticky molecules on its surface. White blood cells latch on, and those cells produce tissue factor, a protein that kicks off the clotting chain reaction.2PubMed Central. New insights into the mechanisms of venous thrombosis This is why prolonged immobility is such a consistent risk factor for deep vein thrombosis: when the calf muscles are not contracting, blood pools in exactly the spots most vulnerable to clot formation.
In arteries, the usual trigger is atherosclerosis, the buildup of fatty plaques inside vessel walls. A plaque can quietly grow for years, then suddenly rupture or erode. When the inner contents of a plaque are exposed to flowing blood, platelets swarm the site and the clotting cascade fires, producing a clot that can partially or completely block the artery.3PubMed Central. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease This is the mechanism behind most heart attacks and many strokes. An arterial clot can also break off and travel downstream. In the brain’s blood supply, atherosclerotic disease of the neck and skull arteries leads to stroke through either local clot formation at the plaque or embolism, where a fragment travels to plug a smaller vessel further along.4PubMed. Mechanisms of ischemic stroke secondary to large artery atherosclerotic disease
Major Risk Factors
The list of things that raise your chances of a thromboembolic event is long, but a few stand out because of how dramatically they shift the odds.
Surgery and trauma top the list. Major operations, multiple injuries, and hip fractures are each considered reason enough on their own for doctors to start clot prevention measures. Spinal cord injuries that paralyze the lower limbs carry similarly high risk.5PubMed. Risk factors for venous thromboembolism Beyond those high-risk triggers, the same source identifies previous clot history, advancing age, heart or lung failure, prolonged bed rest, central venous catheters, and estrogen-based medications as additional contributors.
Immobility deserves special attention because it is so common and so often underestimated. In hospitalized medical patients, being immobile for more than three days roughly tripled the odds of developing a clot in the deep veins closest to the trunk, compared to patients who were moving around. Interestingly, during the first three days, clot rates were similar between mobile and immobile patients; the divergence appeared after day four.6PubMed. Relevance of immobility as a risk factor for symptomatic proximal and isolated distal deep vein thrombosis in acutely ill medical inpatients This finding matters outside the hospital too. Sedentary behavior paired with obesity has been linked to life-threatening clots in adolescents, particularly in cases involving prolonged video game sessions.7PubMed Central. Obesity, sedentary lifestyle, and video games: The new thrombophilia cocktail in adolescents
Cancer raises the risk of venous thromboembolism by roughly four to seven times compared to people without cancer.8PubMed. Trousseau’s syndrome: cancer-associated thrombosis The increased risk comes from the cancer itself, which can release substances that activate clotting, and also from treatments like chemotherapy and surgery. An unexplained blood clot is sometimes the first sign that leads to a cancer diagnosis.
Hormones and Clotting Risk
Estrogen-containing medications, including combined oral contraceptives and hormone replacement therapy, increase the risk of both arterial and venous blood clots.9PubMed Central. Estrogen and thrombosis: A bench to bedside review The mechanisms behind this are remarkably wide-ranging. Estrogen raises levels of certain clotting factors while lowering the body’s natural anticoagulant proteins. It also makes platelets stickier, interferes with the system that dissolves clots, and triggers a cascade of inflammatory changes that nudge the entire hemostatic system toward clotting.10PubMed Central. Combined Oral Contraceptives and the Risk of Thrombosis
For most young, healthy people taking oral contraceptives, the absolute risk of a clot remains small. But if you also carry an inherited clotting tendency, the combined effect can be much larger than either factor alone. This is why doctors sometimes screen for inherited thrombophilia before prescribing estrogen-containing contraception, especially if you have a family history of clots.
Inherited Clotting Disorders
Some people are born with a blood that tips too easily toward clotting. The first inherited clotting condition, antithrombin deficiency, was described over fifty years ago. Since then, researchers have identified a range of genetic variants that raise clot risk, including deficiencies in protein C and protein S, the Factor V Leiden mutation, and the prothrombin G20210A mutation.11PubMed. Thrombophilia, risk factors and prevention These conditions generally increase the level of clot-promoting proteins or decrease the level of natural anticoagulant proteins, leaving the blood in a more clot-ready state.
Having one of these inherited conditions does not guarantee you will develop a clot. Many carriers go their entire lives without an event. The risk becomes meaningful when an inherited tendency combines with an acquired trigger: surgery, pregnancy, a long flight, or estrogen use. This “two-hit” pattern is one reason thromboembolic events so often seem to strike out of nowhere. The genetic predisposition was always there; a situational trigger just tipped the balance.
Recognizing the Symptoms
Thromboembolic events can look very different depending on where the clot ends up. The symptoms are driven by which blood vessel is blocked and what tissue is being starved of blood flow.
A deep vein thrombosis in the leg typically causes swelling of the entire limb or noticeable enlargement of one calf compared to the other. You might see dilated veins on the surface of the leg, and the limb often feels warm and tender.12PubMed. Clinical presentation of deep vein thrombosis and pulmonary embolism The tricky part is that these signs overlap with many other conditions, including muscle strains and infections, so clinical judgment and testing are needed to confirm the diagnosis.
Pulmonary embolism, where a clot travels from the legs to the lungs, announces itself differently. Sudden shortness of breath, chest pain that may worsen with breathing, a rapid heart rate, and sometimes coughing up blood are the hallmark symptoms.12PubMed. Clinical presentation of deep vein thrombosis and pulmonary embolism Large pulmonary emboli can cause a dramatic drop in blood pressure and loss of consciousness. A PE is a medical emergency because it can quickly become fatal if a large enough portion of the lung’s blood supply is cut off.
When a clot blocks an artery feeding a limb, the symptoms come on abruptly: pain, numbness, coldness, and a pale or mottled appearance in the affected arm or leg. As the ischemia worsens, you may lose sensation and eventually muscle function.13PubMed Central. Acute Limb Ischemia Arterial emboli most commonly affect the legs or the brain, the latter producing the familiar symptoms of stroke: sudden weakness on one side of the body, slurred speech, or loss of vision.14PubMed Central. Arterial embolism
How Thromboembolic Events Are Diagnosed
If a doctor suspects a blood clot, the workup usually starts with a clinical probability assessment and a blood test called D-dimer. D-dimer measures a protein fragment that appears when a clot is being broken down. It is very good at ruling out a clot when the result is negative, with sensitivity estimates ranging from 80% to 100% depending on the type of assay used.15PubMed Central. D‐dimer test for excluding the diagnosis of pulmonary embolism The problem is specificity: many things besides clots can raise D-dimer levels, including inflammation, infection, recent surgery, and simply being older. False positives are especially common in people over 65.
Because of this limitation, a positive D-dimer alone does not confirm a clot. It must be followed up with imaging. For suspected DVT, that usually means compression ultrasound of the leg veins. For suspected pulmonary embolism, CT pulmonary angiography is the standard next step. The D-dimer test works best as a gatekeeper: a normal result in a patient with low clinical suspicion means you can safely avoid the imaging scan.16PubMed. D-Dimer for venous thromboembolism diagnosis: 20 years later
Preventing Clots in the Hospital
Most hospital-based clot prevention falls into two categories: blood thinners and mechanical devices. Anticoagulants like heparin or low-molecular-weight heparin reduce the blood’s ability to form clots, while antiplatelet drugs like aspirin prevent platelets from clumping together. The choice between antiplatelet therapy, anticoagulation, or both depends on the specific clinical situation and bleeding risk.17PubMed Central. Antiplatelet, anticoagulant or both? A tool for pharmacists
For patients who cannot take blood thinners because of bleeding risk, intermittent pneumatic compression devices offer an alternative. These are inflatable sleeves wrapped around the legs that periodically squeeze to keep blood moving. A large meta-analysis found that these devices cut DVT rates roughly in half compared to no prevention, bringing rates down from about 17% to 7%. They also reduced pulmonary embolism and carried a lower bleeding risk than pharmacological prevention.18PubMed. Stratified meta-analysis of intermittent pneumatic compression of the lower limbs to prevent venous thromboembolism in hospitalized patients In stroke patients who were immobile, these compression devices reduced DVT from about 12% to about 9%, and there were hints of improved survival as well.19PubMed. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3) Combining mechanical compression with blood thinners further reduced clot risk compared to either approach alone.
Exercise and Everyday Prevention
Outside the hospital, physical activity provides meaningful protection. A systematic review pooling data from large cohort studies found that the most physically active people had roughly a 13% lower risk of venous thromboembolism compared to the least active, after adjusting for body weight and other factors.20PubMed Central. Physical activity and risk of venous thromboembolism: systematic review and meta-analysis of prospective cohort studies When body weight was not accounted for, the protective effect was even larger, suggesting that part of how exercise helps is by keeping weight in check, which in turn reduces clot risk.
You do not need to train for a marathon to benefit. The key is avoiding prolonged immobility. On long flights or car rides, getting up to walk every couple of hours, flexing your ankles, and staying hydrated all help keep blood moving through those vulnerable valve pockets. If you have a desk job or spend hours gaming, the same principle applies: regular movement breaks matter more than the intensity of your exercise sessions.
Air Pollution and Clot Risk
An underappreciated contributor to thromboembolic risk is the air you breathe. Research has found that acute exposure to fine particulate matter, the tiny pollution particles known as PM2.5, pushes the blood toward a more clot-prone state.21PubMed Central. Ambient air pollution and thrombosis The mechanisms involve inflammation, disruption of the vessel lining, increased blood pressure, and destabilization of atherosclerotic plaques.22PubMed. Ambient Air Pollution and Atherosclerosis: Insights Into Dose, Time, and Mechanisms
This is not just a theoretical concern. Population studies have consistently linked higher pollution levels to increased rates of heart attacks and strokes, which are arterial thromboembolic events. The effect is most pronounced during short-term pollution spikes, such as during wildfire smoke events or heavy traffic exposure. People who already have cardiovascular risk factors are especially vulnerable, but even healthy individuals are affected to some degree.
How Your Gut Bacteria Can Influence Clotting
One of the more surprising recent discoveries in thrombosis research involves the gut microbiome. When you eat foods rich in certain nutrients, particularly choline, lecithin, and carnitine found in red meat, eggs, and some dairy, gut bacteria convert them into a compound called trimethylamine, which your liver then transforms into TMAO (trimethylamine N-oxide). In a study of over 4,000 people, plasma TMAO levels independently predicted the risk of having a heart attack or stroke over the following three years. Laboratory work showed that TMAO directly makes platelets more reactive, priming them to clump together more aggressively in response to normal activation signals.23PubMed Central. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk
This does not mean that eating an egg will give you a blood clot. It does suggest that the composition of your gut bacterial community, shaped by long-term dietary patterns, can shift your baseline clotting tendency. People with gut bacteria that produce more TMAO may carry a chronically higher thrombotic risk. The practical takeaway is still being worked out, but it adds a new dimension to the familiar advice about limiting heavily processed red meat and diversifying your diet.
Stress and the Clotting System
Psychological stress, both acute and chronic, can make blood more prone to clotting. Stress activates the fight-or-flight nervous system and the body’s hormonal stress response. These systems, in turn, alter platelet behavior, boost clotting factor levels, impair the vessel lining, and trigger widespread low-grade inflammation.24PubMed Central. Impact of Acute and Chronic Stress on Thrombosis in Healthy Individuals and Cardiovascular Disease Patients
Chronic stress is especially concerning because of its sustained inflammatory effects. Stress-related inflammatory molecules like IL-6 and C-reactive protein promote clot formation and impair the body’s ability to dissolve clots that do form. Over time, this inflammation can damage the vessel lining, creating a surface that attracts platelets and accelerates clotting.25PubMed Central. Stress-induced hemostasis: mechanisms and implications for health – Section: Mechanisms of stress-induced hemostatic changes For people who already have cardiovascular disease or other risk factors, chronic stress may be the additional push that triggers an actual event.
When a Clot Crosses From Vein to Artery
Most thromboembolic events follow predictable routes: venous clots travel to the lungs, and arterial clots block arteries in the heart, brain, or limbs. But in some people, a venous clot can cross into the arterial circulation and cause a stroke or block an artery somewhere else entirely. This is called paradoxical embolism, and it usually happens through a patent foramen ovale, a small flap-like opening between the right and left upper chambers of the heart that never fully closed after birth. About one in four adults has this opening. Paradoxical embolism accounts for roughly 5% of all strokes and about 10% of strokes in younger patients.26JAMA. Patent Foramen Ovale and Stroke: A Review
This matters clinically because a young person who has a stroke without obvious arterial disease may benefit from closure of that opening. If the evaluation turns up a DVT and a PFO in someone who just had a stroke, the story suddenly makes sense: the clot formed in a vein, slipped through the heart defect, and lodged in a brain artery. Recognizing this pathway changes both the diagnosis and the approach to prevention, since the focus shifts from arterial disease management to venous clot prevention and potentially a procedure to seal the PFO.