Epidemiology

Peripheral artery disease, which creates the conditions for thrombosis to occur, affects more than 200 million people around the world. In the United States alone, around 12 million adults age 40 or older live with this condition, and the number increases dramatically with age. Nearly half of all people aged 85 and older are affected by peripheral artery disease.^[1][2]

The condition does not affect everyone equally. Black individuals face a significantly higher risk compared to non-Hispanic white people, particularly after age 50 in males and age 60 in females. Men are generally at greater risk than women. The global disease burden has been increasing steadily, with a 23.5% rise in prevalence between 2000 and 2010. More than 6.5 million Americans over age 40 have peripheral artery disease, yet the condition often goes unrecognized and untreated, leading to serious complications including thrombosis.^[2][4][12]

Causes

The development of thrombosis in peripheral arteries is closely linked to atherosclerosis, which means hardening of the arteries due to plaque buildup. Plaque is a sticky substance made up of fat, cholesterol, calcium, and other materials found in the blood. Over time, this plaque gradually accumulates inside the artery walls, making them stiff and narrowing the space where blood can flow.^[2][4]

What makes thrombosis particularly dangerous is how it develops on top of existing plaque. Arteries normally have a smooth inner lining that prevents blood from clotting and allows steady blood flow. When you have peripheral artery disease, plaque slowly forms inside your artery walls. Many of these plaque deposits are hard on the outside but soft on the inside. This hard surface can crack or tear, exposing the soft interior. When this happens, platelets, which are disc-shaped particles in your blood that help it clot, rush to the damaged area. Blood clots then form around the plaque, making the artery even narrower or blocking it completely.^[2][10]

Sudden blockage of an artery can result when a blood clot forms in an artery that is already narrowed from plaque. It can also happen when a clot breaks off from somewhere else in the body, such as the heart or aorta, travels through the bloodstream, and lodges in an artery downstream. Sometimes, an atheroma (a fatty deposit) can rupture into the blood vessel, triggering the sudden formation of a blood clot. Less commonly, other conditions can cause peripheral artery blockage, including abnormal growth of muscle in the artery wall, inflammation of blood vessels, or pressure from an outside mass like a tumor.^[5]

Risk Factors

Several factors significantly increase your chances of developing peripheral artery disease and subsequent thrombosis. The most significant risk factors include high blood pressure, diabetes, chronic kidney disease, high cholesterol, and smoking. Research shows that having multiple risk factors compounds your danger. The odds of having peripheral artery disease increase with each additional risk factor, from a 1.5-fold increase with one risk factor to a tenfold increased risk with three or more risk factors.^[12]

Smoking stands out as particularly harmful. In one large study, more than 80 percent of patients with peripheral artery disease were current or former smokers. The cardiovascular death rates of current smokers with peripheral artery disease are more than double that of those who have never smoked. Even after diagnosis, people who continue smoking are much more likely to have a heart attack and die from heart disease complications than people who quit.^[12]

Age is another major risk factor, as peripheral artery disease and thrombosis become more common with aging. Being physically inactive, having obesity, and having high levels of homocysteine (a component of protein) in your blood also increase your risk. Males face higher risk than females. Having a family history of atherosclerosis puts you at greater risk as well. Low levels of HDL cholesterol (the “good” cholesterol) are also associated with increased risk of death in people with peripheral artery disease.^[4][5][12]

Certain medical conditions increase the risk of blood clot formation, which can lead to sudden artery blockage. These include atrial fibrillation (an irregular heart rhythm), other heart disorders, and clotting disorders. Inflammation of blood vessels, which may be due to an autoimmune disorder, can also trigger sudden blockage of an artery.^[5]

Symptoms

The symptoms of peripheral artery thrombosis depend on which artery is affected, how completely it is blocked, and whether the blockage developed gradually or suddenly. Usually, more than half of the artery’s interior must be blocked before symptoms appear. Gradual narrowing typically results in less severe symptoms than sudden blockage.^[5]

Many people with peripheral artery disease have no symptoms at all, especially in the early stages. About 40 percent of people with the condition experience no leg symptoms. When symptoms do occur, the most common is leg discomfort during physical activity. This happens because your arteries cannot keep up with your muscles’ increased demand for blood when you move. You might feel pain, cramping, numbness, or fatigue in your calves, thighs, or buttocks. This discomfort, called claudication, starts during activities like walking or climbing stairs and stops when you stop moving, typically within 10 minutes.^[1][2][4]

As peripheral artery disease progresses, you may develop leg or foot pain even when resting. This burning or aching pain in your legs, feet, or toes often happens when you are lying flat. Dangling your leg or feet over the edge of your bed may relieve this pain. Exactly where you feel discomfort depends on which artery is narrowed. If your lower aorta or iliac arteries in your pelvic area are affected, you will feel discomfort in your buttocks, hip, or thigh. If your femoral or popliteal arteries in your thigh and knee area are narrowed, you will feel discomfort in your calf. Males may also experience erectile dysfunction when the lower aorta or iliac arteries are narrowed.^[2][10]

Other symptoms include coldness in your lower leg or foot, with one leg or foot feeling colder to the touch than the other due to restricted blood flow. Your skin may change color, turning pale, bluish, or having a shiny appearance. Poor circulation can slow down nail and hair growth on your legs and feet, leading to little or no hair on the toes, feet, or lower legs. An absent or weak pulse in your feet or legs is another sign.^[1][4]

Foot and toe ulcers are serious symptoms. These are wounds on your skin that may become infected and take a long time to heal. When peripheral artery disease becomes severe, you may develop critical limb ischemia, where blood flow is so restricted that tissue damage occurs. Symptoms include pain during rest, sores, infections, and tissue death called gangrene. Gangrene is a life-threatening complication that may require amputation of the affected body part.^[2][4]

Prevention

Preventing peripheral artery thrombosis starts with addressing the underlying risk factors and making lifestyle changes. These measures can not only reduce your risk of developing the condition but may also slow its progression if you already have it. In some cases, you may even be able to reverse symptoms and avoid more serious interventions.^[15]

One of the most important steps you can take is to quit smoking if you smoke. Stopping smoking will significantly reduce your risk of peripheral artery disease getting worse and prevent other serious cardiovascular diseases from developing. Research consistently shows that people who smoke after receiving their diagnosis are much more likely to have a heart attack and die from heart disease complications than people who quit. Quitting smoking improves not only your cardiovascular health but also your lung function and overall wellbeing.^[11][18]

Regular exercise is essential for preventing and managing peripheral artery disease. Physical activity boosts blood circulation, strengthens muscles, and enhances cardiovascular health. Evidence suggests that regular exercise helps reduce the severity and frequency of symptoms while lowering the risk of developing other cardiovascular diseases. Exercise can also improve your self-esteem, mood, sleep quality, and energy. Walking is particularly beneficial because it promotes the development of collateral circulation, where smaller blood vessels form to bypass blocked arteries, gradually increasing blood flow to your legs.^[11][18][19]

Eating a balanced and nutritious diet helps reduce risk factors like high cholesterol, high blood pressure, and diabetes. Focus on whole foods including fruits, vegetables, whole grains, lean proteins, and healthy fats. The Mediterranean diet may be particularly beneficial for preventing peripheral artery disease. This eating pattern emphasizes extra-virgin olive oil, nuts, beans, and limits dairy, red meat, and highly processed foods. It has been linked to more stable blood sugar levels and lower cholesterol. Limiting saturated and trans fats, refined sugars, and sodium can reduce inflammation and improve arterial health. Drinking plenty of water throughout the day helps optimize blood flow and prevent dehydration.^[19]

Managing other health conditions is crucial for prevention. If you have diabetes, keeping your blood sugar levels well controlled is essential. Properly managing diabetes may involve lifestyle changes like eating a healthy, balanced diet and taking medicines to lower your blood sugar. If you have high blood pressure or high cholesterol, working with your healthcare provider to control these conditions will reduce your risk. Managing your weight and cutting down on alcohol are also important lifestyle changes.^[11][18]

Pathophysiology

Understanding how peripheral artery thrombosis develops requires looking at the changes that occur in your blood vessels. Normal arteries are shaped like hollow tubes with smooth inner linings that prevent blood from clotting and allow steady blood flow. When you have atherosclerosis, this normal structure and function change dramatically.^[2][10]

In atherosclerosis, deposits of cholesterol and other fatty materials, called atheromas or atherosclerotic plaques, develop in the walls of arteries. These deposits gradually narrow the interior space of the artery, reducing blood flow. Calcium, which is normally carried in the blood, may also accumulate in the walls of the blood vessels, making the arteries stiff and further narrowing the passage. As the plaque builds up over time, the artery becomes less flexible and the amount of blood that can flow through decreases.^[3][5]

An inadequate blood supply leads to insufficient oxygen levels in body tissues, a condition called ischemia. Ischemia may develop suddenly or gradually depending on how the artery becomes blocked. When blood flow is reduced, the muscles and tissues that depend on that artery do not receive enough oxygen and nutrients. During physical activity, when muscles need more blood and oxygen, this shortage becomes especially noticeable, causing pain or cramping. When you rest, the demand decreases, so the symptoms often go away.^[5]

The development of thrombosis happens when the plaque deposits become unstable. Many plaque deposits have a hard outer surface but are soft inside. When the hard surface cracks or tears, the soft interior is exposed to the flowing blood. Platelets, which are small blood cell fragments that help blood clot, recognize this tear as an injury. They rush to the site and begin sticking together, forming a clot. This clot can quickly grow, making the narrowed artery even more blocked or completely cutting off blood flow.^[2][10]

Sometimes a blood clot forms elsewhere in the body, such as in the heart during atrial fibrillation, then breaks loose and travels through the bloodstream. When this traveling clot, called an embolus, reaches a narrowed artery in the leg, it can lodge there and suddenly block blood flow. The result is the same: tissues downstream from the blockage are deprived of oxygen and nutrients. If the blockage is severe enough and lasts long enough, the affected tissues can be damaged or die, a condition called gangrene.^[5]

The body tries to compensate for reduced blood flow by developing new, smaller blood vessels that create alternative routes around the blockage. This process, called collateral circulation, happens gradually over time. However, these smaller vessels may not be able to provide as much blood flow as the original artery, especially during physical activity when demand is higher. This explains why symptoms like claudication occur with exercise but improve with rest.^[19]