Introduction

What are risk factors? 

Risk factors are characteristics that increase the chance of developing a disease or health condition.¹ It is essential to understand risk factors to allow for the prevention, early detection, and management of conditions such as thrombosis.^2,3

What is thrombosis?

Thrombosis is the formation of a thrombus (blood clot) within a blood vessel. A thrombus, made up of red blood cells, fibrin, and platelets, is formed in response to injury.^5,6 Thrombosis is a serious condition because, depending on its level of obstruction, location, and movement, it can lead to life-threatening complications such as stroke and myocardial infarction.⁵

Types of thrombosis 

Arterial thrombosis refers to the formation of blood clots in arteries, a type of blood vessel that carries oxygenated blood from the heart to the rest of the body. Venous thrombosis refers to the formation of blood clots in veins, a type of blood vessel that carries deoxygenated blood from the body to the heart.⁴

This article mentions venous thromboembolism. This term refers to the formation of blood clots within veins and affects 1 to 2 people per 1000 people each year, with two-thirds of all cases being deep vein thrombosis and one-third of cases being pulmonary embolism.²⁸

Risk Factors for Thrombosis 

Non-modifiable risk factors

Non-modifiable risk factors, such as genetics, age, and race, are risk factors that cannot be altered. 

Genetic Factors

Inherited clotting disorders

Hemostasis is a highly coordinated process whereby the body repairs damaged blood vessels, forms blood clots, and maintains blood in a fluid state. Hemostasis involves the coagulation cascade, a complex series of events involving several enzymes and clotting factors (specific types of proteins) that enable blood to clot.⁷ Inherited clotting disorders are genetic conditions that affect the body’s ability to form blood clots. 

Factor V is a clotting factor that plays a role in the coagulation cascade; however, a mutation in the F5 gene leads to Factor V Leiden, an inherited clotting disorder that increases hypercoagulability (the increased tendency of blood to clot), thereby increasing the risk of thrombosis and, subsequently, deep vein thrombosis.^8,9 

Prothrombin is another clotting factor involved in the coagulation cascade, which helps form blood clots. A prothrombin G20210A mutation leads to increased prothrombin levels and subsequently increased tendency to form blood clots and increased risk of venous thrombosis. ^8,10

Anticoagulant deficiencies

Antithrombin, protein C, and protein S are natural anticoagulants, proteins which regulate hemostasis by inactivating clotting factors involved in the coagulation cascade.¹¹ These anticoagulants limit the formation of blood clots to only the specific areas of damage, thereby preventing the formation of large clots that would occlude the blood vessel and limit the normal flow of blood.¹² 

Mutations in the SERPINC1, PROC, and PROS1 genes lead to deficiencies in antithrombin, protein C, and protein S, respectively.⁸ While rare, anticoagulant deficiencies lead to thrombophilia, a condition in which the blood clots more easily, thus increasing the chance of thrombosis.^8,12

Age

Venous thrombosis is rare in young people, with its incidence being less than one young person per 10,000 affected each year; however, the incidence of venous thrombosis increases with age by approximately 1% per year in the elderly.¹⁹

Sex

The incidence of thrombosis differs by sex. Men have a higher intrinsic risk of venous thromboembolism than women, regardless of age, with the age-adjusted incidence rate among men being 130 per 100,000 person-years compared to 100 per 100,000 person-years in women.^20,21

That being said, oestrogen-containing contraception, hormone replacement therapy, gender‐affirming hormone therapy, and pregnancy also contribute to increased risk of venous and arterial thrombosis.²¹

Race 

Compared to White populations, the risk of venous thromboembolism was 35% greater in Black populations, 30% lower in Hispanic populations, and 74% lower in Chinese populations.²⁹ The racial difference in venous thromboembolism incidence could be due to racial differences in risk factors (such as obesity and inherited clotting disorders) prevalence.³⁰ 

Lifestyle and Environmental Factors

Physical inactivity

A sedentary lifestyle, prolonged bed rest, and immobility can increase the risk of developing blood clots, also known as thrombosis. Muscle contraction in the lower extremities (from your hips to your toes) is needed to help blood flow back up to the heart. Physical inactivity and a lack of lower extremity muscle contraction could then lead to reduced blood flow, venous stasis, and accumulation of thrombin, which may overcome anticoagulant pathways and lead to thrombosis. .^17,18

Obesity

Obesity refers to the excessive accumulation of fat. You are classed as obese if you have a body mass index (BMI) greater than 30 kg/m². Compared to those with a normal BMI (18.5 to 24.9 kg/m²), obese people have a 2 to 5-fold increased risk of venous thromboembolism ¹³

Obesity can lead to insulin resistance and increased risk of diabetes; however, chronic inflammation and impaired fibrinolysis as a result of obesity have been identified as the mechanisms responsible for obesity-induced thrombosis.¹⁴

Smoking

Smoking, tobacco use, and second-hand exposure to tobacco smoke increase the risk of coronary thrombosis and venous thromboembolism by a number of mechanisms but chiefly through altering the function of endothelial cells, platelets, fibrinogen, and clotting factors.^15,16

Medical Conditions

Cardiovascular disease

Cardiovascular diseases are a group of conditions that affect the heart and blood vessels. These conditions are often associated with atherosclerosis, the accumulation of fats on blood vessel walls, which develop into plaques that occlude the blood vessel. Inflammation and damage to the blood vessel can cause the plaque to rupture, exposing an area of damage that triggers the coagulation cascade to form a thrombus.³³

Cancer

Cancer is a condition caused by the uncontrolled growth of abnormal cells. People who have cancer have a higher risk of developing blood clots due to a condition called cancer-associated thrombosis. Cancer patients have a higher incidence rate of arterial thrombosis (compared to matched controls), but venous thromboembolism is more common, affecting approximately 4% to 20% of cancer patients.²² 

The mechanism that causes cancer patients to be predisposed to thrombosis is not yet fully understood, but the presence of inflammatory cytokines and genetic changes influencing the coagulation cascade, prothrombotic chemotherapy drugs, and tumours damaging blood vessels are thought to promote a hypercoagulable state.^22,23

Surgical and Trauma-Related Factors

Surgery

Postoperative thromboembolism is a serious complication of surgery with high incidence rates following total knee replacement, hip replacement, cardiac, and spine surgery.²⁴ Deep vein thrombosis is another complication of surgery, which affects vascular and cardiac surgery patients more frequently than general surgery patients.²⁵

Trauma or injury

Trauma refers to the sudden onset of severe tissue damage resulting from a blunt, penetrating or deceleration source of injury. 

Patients with rib fractures are at higher risk of venous thromboembolism, with the risk increasing as the number of fractured ribs increases.²⁶ Patients with pelvic, femoral, and tibial fractures are at higher risk of deep vein thrombosis.²⁷

Traumatic rib, pelvic and lower-extremity fractures can lead to the development of thrombosis because of the hypercoagulable state, injury to blood vessels and reduced blood flow caused by the impact of the trauma, decreased mobility, and treatments such as sedative muscle relaxants, indwelling deep venous catheters.^26,27

Infections

An infection is an illness caused by pathogens such as bacteria, viruses and fungi. 

The main difference between infection-associated thrombosis and thrombosis associated with other episodes is the presence of a pathogen and its products, which promote inflammation. Inflammation, in turn, activates platelets and may also result in endothelial damage, fibrin deposition, and ultimately thrombus formation.³¹

FAQs

Is thrombosis dangerous? 

Thrombosis can be dangerous because it has the potential to cause life-threatening conditions such as a stroke and heart attack if the thrombus becomes dislodged and blocks important blood vessels, such as the coronary arteries or cerebral arteries, which supply blood to the heart and brain, respectively.³² 

What are the signs of thrombosis?

The signs and symptoms of thrombosis depend on the severity and location of the thrombus. For example, deep vein thrombosis can cause the affected area (such as the leg) to look and feel swollen, red, warm and painful. Those with a pulmonary embolism typically present with shortness of breath, chest pain, back pain, and dizziness. Cardiac events due to arterial thrombosis, for example, in the coronary artery, can cause left-sided chest pain, which can spread to the jaw and left arm. Thrombosis in the cerebral arteries can cause symptoms such as headache, difficulty speaking, one-sided muscle weakness, confusion, and changes in vision.³²

Can thrombosis be prevented?

By identifying risk factors relevant to you, you can make adjustments to your lifestyle to reduce the risk of developing thrombosis. Examples of lifestyle modifications include quitting smoking, increasing physical activity through exercise, and losing weight.³² Surgical patients may be given anticoagulant drugs and are advised to start walking early on following their surgical procedure to help prevent thrombosis.²⁶ Your doctor may also advise you regarding your use of oral contraceptives.³²

Summary

• Thrombosis refers to the formation of a thrombus (blood clot) within an arterial or venous blood vessel
• Risk factors are characteristics that increase your chance of developing a condition or disease
• Some risk factors of thrombosis are characteristics that you cannot change, such as increasing age, race, and genetics 
• Other risk factors include physical inactivity, obesity, cardiovascular disease, surgery and infection
• Understanding of the mechanisms behind risk factors leading to thrombosis is evolving but fundamentally involves damage to blood vessels and changes in various components of the coagulation cascade