The causes of blood clots fall into three basic categories — and doctors have known this since the 1800s. A German physician named Rudolf Virchow identified what we now call Virchow’s triad: damage to blood vessel walls, sluggish blood flow, and blood that clots too easily. Every cause on this list traces back to one (or more) of those three mechanisms.
Some causes you can’t change — your genetics, your age, your family history. But many of the most common causes of blood clots are modifiable, meaning you can take concrete steps to lower your risk. Here’s the full breakdown, with the data behind each one.
What Exactly Is a Blood Clot?
A blood clot (thrombus) is a gel-like mass of blood that forms when platelets and clotting proteins solidify inside a blood vessel. Clotting is essential — without it, a paper cut could be fatal. The problem starts when clots form where they shouldn’t, or when they don’t dissolve after doing their job.
Clots in veins (venous thrombosis) and clots in arteries (arterial thrombosis) behave differently and have somewhat different causes. Venous clots — including deep vein thrombosis (DVT) and pulmonary embolism (PE) — affect roughly 900,000 Americans per year and kill up to 100,000 annually, making venous thromboembolism (VTE) the third leading vascular cause of death after heart attack and stroke.
The 12 Major Causes of Blood Clots
I’ve organized these into non-modifiable causes (the ones baked into your biology) and modifiable causes (the ones you can actually do something about).
Non-Modifiable Causes
| Cause | How It Increases Clot Risk | Relative Risk Increase |
|---|---|---|
| Factor V Leiden mutation | Makes activated protein C less effective at shutting down clotting | 3–8x (heterozygous); 50–80x (homozygous) |
| Prothrombin gene mutation (G20210A) | Leads to higher prothrombin levels, promoting clot formation | 2–5x |
| Protein C, Protein S, or Antithrombin deficiency | Removes natural “brakes” on the clotting cascade | 5–50x (varies by type) |
| Age over 60 | Vessels stiffen, mobility decreases, clotting factors increase | Risk roughly doubles per decade after 40 |
| Family history of VTE | Suggests inherited thrombophilia (even without identified mutation) | 2–4x |
Factor V Leiden is the most common inherited clotting disorder in people of European descent, carried by about 5% of Caucasians. Most carriers never develop a clot — but combine it with another risk factor (say, oral contraceptives), and the risk multiplies dramatically.
Modifiable and Situational Causes
1. Prolonged immobility. Sitting for 4+ hours — whether on a long flight, at a desk, or in a hospital bed — slows venous blood flow in the legs. Studies show flights over 8 hours increase DVT risk by 2–4x. Post-surgical bed rest is one of the single biggest risk factors for hospital-acquired clots.
2. Major surgery or trauma. Orthopedic procedures (hip and knee replacements especially) carry DVT rates of 40–60% without prophylaxis. Tissue damage activates the clotting cascade directly. This is why surgeons routinely prescribe blood thinners after these operations.
3. Obesity (BMI ≥30). Excess weight compresses pelvic veins, slows venous return, and creates a chronic inflammatory, pro-thrombotic state. Obesity roughly doubles the risk of VTE.
4. Smoking. Cigarette smoke damages the endothelial lining of blood vessels and increases fibrinogen levels (a key clotting protein). Smokers face a 2–3x higher risk of arterial clots and a measurably increased risk of venous clots.
5. Hormonal factors. Combined oral contraceptives increase VTE risk 3–4x. Hormone replacement therapy roughly doubles it. Pregnancy increases clot risk 4–5x — and the postpartum period (especially the first 6 weeks) is actually the highest-risk window.
6. Cancer. Active malignancy is one of the strongest acquired risk factors, raising VTE risk 4–7x. Certain cancers — pancreatic, brain, lung, ovarian — are particularly notorious. Chemotherapy compounds this further. A blood clot is sometimes the first sign of an undiagnosed cancer.
7. COVID-19 and other infections. Severe COVID-19 causes a hypercoagulable state through widespread inflammation and endothelial damage. Early pandemic data showed ICU-admitted COVID patients had VTE rates of 25–30% even with prophylaxis.
Virchow’s Triad: The Framework Doctors Actually Use
When evaluating a patient for clot risk, I think in terms of Virchow’s triad. It simplifies the dozens of risk factors into three core problems:
- Endothelial injury — Surgery, trauma, smoking, infections, IV catheters
- Blood stasis (slow flow) — Immobility, obesity, heart failure, varicose veins, compression from tumors
- Hypercoagulability (blood that clots too easily) — Genetic mutations, cancer, pregnancy, hormonal therapy, dehydration
Most dangerous clots happen when two or more of these factors overlap. A woman with Factor V Leiden who starts birth control pills and then takes a 12-hour flight has stacked three risk layers — and her absolute risk becomes clinically significant.
Symptoms You Shouldn’t Ignore
DVT symptoms (usually in one leg):
- Swelling that develops over hours to days
- Calf or thigh pain that feels like a deep cramp
- Skin that’s warm, red, or discolored
- Veins that look more prominent than usual
Pulmonary embolism symptoms (a medical emergency):
- Sudden shortness of breath with no obvious cause
- Sharp chest pain that worsens with deep breathing
- Coughing up blood or pink-tinged sputum
- Rapid heart rate, lightheadedness, or passing out
PE kills fast. About 25% of PE cases present as sudden death — the person had no prior symptoms. If you have unexplained shortness of breath plus leg swelling, call 911. Don’t drive yourself to the ER.
When to See a Doctor
Go to the emergency room immediately if you have chest pain, sudden difficulty breathing, or cough up blood — especially if you have any known risk factors.
See your doctor within 24 hours if you notice new, unexplained swelling in one leg, particularly with pain or redness.
Schedule a routine visit if you have a strong family history of blood clots (two or more first-degree relatives) and want to discuss whether thrombophilia testing makes sense. Testing typically includes Factor V Leiden, prothrombin gene mutation, antithrombin levels, protein C and S levels, and antiphospholipid antibodies.
Frequently Asked Questions
Can dehydration cause blood clots?
Yes. Dehydration concentrates the blood and makes it more viscous, which promotes clot formation. This is one reason long flights are risky — cabin air is extremely dry, and many travelers don’t drink enough water. It’s a contributing factor, though it rarely causes clots on its own without other risk factors present.
At what age should I worry about blood clots?
VTE can strike at any age, but risk climbs steeply after 40 and roughly doubles with each subsequent decade. That said, young women on birth control, anyone immobilized after surgery, and people with inherited clotting disorders can develop clots in their 20s and 30s. Age alone isn’t the deciding factor — it’s the combination of risk factors that matters.
Can stress cause blood clots?
Chronic stress raises cortisol and catecholamines, which can increase clotting factor activity and platelet aggregation. There’s epidemiological evidence linking high-stress states with increased cardiovascular events. However, stress alone is unlikely to cause a clot without other underlying risk factors. Think of it as an amplifier, not a standalone cause.
Do blood clots run in families?
Absolutely. About 5–8% of the general population carries at least one inherited thrombophilia. If a first-degree relative (parent, sibling) had a DVT or PE — especially before age 50 or without an obvious trigger — your own risk is 2–4x higher. Talk to your doctor about whether genetic testing is appropriate.
What’s the difference between a blood clot and a bruise?
A bruise is a superficial collection of blood that leaked from damaged capillaries into the skin and surrounding tissue. It’s visible, generally harmless, and resolves on its own. A blood clot (thrombus) forms inside a blood vessel and can obstruct blood flow or break free and travel to the lungs. They’re fundamentally different conditions, though both involve blood leaving its normal pathway.
