What is venous thromboembolism?

A venous thromboembolism (VTE) is a blood clot that blocks blood flow in a vein. The word "thrombo" refers to a blood clot, while "embolism" means a particle traveling through the bloodstream that causes a blockage. VTE is a condition that can lead to two serious types of blood clots: deep vein thrombosis (DVT), a clot in a deep vein, usually in the legs and pulmonary embolism (PE)—a clot that travels to the lungs.¹ 

What is thrombophilia?

When you get a cut or a bruise, your body acts to stop the bleeding. Platelets (a type of blood cell) and clotting factors (proteins in your blood) team up to form a clot. Once the bleeding stops, the clot naturally dissolves.³

However, some people have a condition called thrombophilia, or hypercoagulability, which makes them more likely to develop blood clots, even without an injury. This occurs when the body either produces excessive clotting protein or insufficient proteins that control clotting. Sometimes, clots don’t dissolve when they should, or the body creates proteins that harm blood vessels.

Thrombophilia can block blood flow, cutting off oxygen to tissues and organs. It can lead to deep vein thrombosis (DVT) (a clot in the leg), pulmonary embolism (PE) (a clot in the lungs), and even serious conditions like heart attacks and strokes.³

It is essential to understand the link between thrombophilia and VTE to provide patients with effective care and prevent complications. Given that VTE can result in serious conditions like PE and DVT, clinicians must evaluate each patient's unique risk factors. Proper evaluation aids in finding the root causes, but testing guidelines are still up for debate. Missed diagnoses and natural interventions can be avoided with clearer guidelines. Patient outcomes, treatment plans, and risk assessment can all be enhanced by more research.⁵

Pathology of venous thromboembolism

Numerous risk factors contribute to the complexity and multifactorial nature of VTE. Virchow's triad, which includes hypercoagulability, vascular endothelial damage, and blood flow stasis, is a key theory explaining the pathophysiology of VTE.⁵

1. Virchow's triad:

• Venous stasis: Low blood flow in the veins, often due to extra immobility, can lead to blood pooling and clot formation
• Hypercoagulability: An increased tendency for blood to clot generated by genetic factors, certain medical conditions, or medications
• Endothelial damage: Injury to the lining of blood vessels can trigger the clotting cascade, promoting thrombus formation⁶

2. Pathogenesis of venous thrombus formation:

• Clot formation: A blood clot forms in a vein, often in the deep veins of the legs or pelvis
• Clot propagation: The thrombus can grow and extend into large veins
• Embolisation: A pulmonary embolism may result from a piece of the thrombus breaking off and moving through the bloodstream
• Pulmonary embolism: This occurs when a clot blocks blood flow in the arteries, reducing the amount of oxygen that reaches the lungs and possibly causing fatal consequences⁶
  

Thrombophilia and its connection to VTE

Numerous genetic mutations that are associated with an increased risk of VTE are included in thrombophilias. Many patients who present with venous thromboembolism (VTE) have either acquired or hereditary thrombophilia. Currently, the most frequently tested hereditary thrombophilias are:^4,8

Genetic thrombophilia (Hereditary risk factors):

• Factor V Leiden mutation
• Prothrombin G20210A mutation
• Protein C deficiency
• Protein S deficiency
• Antithrombin deficiency

A thrombophilia testing panel typically includes lupus anticoagulant, anticardiolipin antibodies, and anti-ß2 glycoprotein 1 antibodies, which are laboratory indicators of acquired thrombophilic antiphospholipid syndrome (APS).^4,7,8 These also include other acquired thrombophilias.

Acquired thrombophilia:

• Antiphospholipid syndrome (APS)
• Cancer-associated thrombosis
• Hormonal factors (oral contraceptives, pregnancy)

Other risk factors for VTE in thrombophilia

Here's a more detailed breakdown of risk factors for VTE in the context of thrombophilia.^4,8

Environmental and lifestyle factors:

• Immobility and prolonged bed rest: Sitting or lying down for long periods, like during bed rest, paralysis, or long trips, slows blood flow and increases the risk of blood clots
• Surgery and trauma: Major surgeries, especially bone surgeries, and serious injuries like broken hips or legs can raise the risk of blood clots due to less movement and changes in blood clotting
• Obesity and smoking: Being overweight and smoking both increase the risk of blood clots. Obesity can make other risk factors worse, while smoking affects blood circulation
• Hormonal therapy (e.g., oestrogen therapy): Birth control pills, hormone treatments, and pregnancy-related hormonal changes can increase clotting, making blood clots more likely
• Pregnancy and postpartum: During pregnancy and after childbirth, the body naturally increases clotting, which raises the risk of blood clots. Compared to non-pregnant patients, pregnant patients have a 5-fold increased risk of VTE during pregnancy

Comorbid conditions:

• Autoimmune diseases: Conditions like inflammatory bowel disease and psoriasis can increase the risk of blood clots
• Cancer: Certain cancers, such as those in the pancreas, lungs, ovaries, stomach, and lymph nodes, make blood clots more likely
• Chronic inflammation: Long-term inflammation in the body can raise the risk of blood clots
• Previous blood clots: If someone has a history of blood clots, they are more susceptible to having another one
• Family history: A family history of blood clots may mean a higher risk due to inherited conditions
  Aging: The risk of blood clots increases with age, especially after 40 and even more after 60
• COVID-19: Infection with COVID-19 has been linked to a higher risk of blood clots

What are the warning signs?

DVT mainly affects the large veins in the lower leg, thigh, or pelvis, almost always on one side of the body at a time. The clot can block blood flow and cause:⁹

• Leg pain or tenderness
• Swelling on legs
• Warmth
• Redness or skin discoloration
• Swollen veins

Pulmonary embolism can be fatal and occurs when a thrombus (blood clot) DVT breaks free from a vein wall, travels to the lungs, and blocks some or all of the blood supply to the lungs, causing:⁹ 

• Shortness of breath
• Chest pain
• Coughing
• Dizziness or fainting
• Fast heartbeat or breathing

How is it diagnosed?

In order to diagnose VTE, your healthcare provider will order imaging scans and blood tests, review your medical history, and conduct a physical examination. D-dimer is a frequently used blood test that checks indications of blood clotting.¹⁰

• For DVT: An ultrasound of the leg is a common test
• For PE: A CT pulmonary angiogram (CTPA) is usually done. If CTPA isn’t available or can’t be used, a ventilation-perfusion (V/Q) lung scan can be an alternative
• Other imaging tests: If the results of earlier tests were insufficient to diagnose or rule out VTE, additional imaging tests examine heart and lung function as well as the flow of blood through your veins

Both imaging tests use special dyes to check for blood clots blocking the arteries in the lungs. For thrombophilia, some tests can help identify individuals at higher risk of VTE, allowing for preventative measures or more targeted treatment strategies.¹¹

• Functional tests: For natural blood-thinning proteins (like protein S, protein C, and antithrombin)
• Activated protein C resistance (APCR) Test: This test screens for the Factor V Leiden mutation, a common genetic change that can increase your risk of blood clot
• PCR analysis: This method looks for specific genetic changes, such as the Factor V Leiden mutation or the prothrombin gene mutation
• Lupus anticoagulant and antiphospholipid antibodies tests: These tests help identify Antiphospholipid Syndrome (APS), a condition that can increase the risk of clots in both veins and arteries

How is it managed?

In individuals with thrombophilia, managing and preventing Venous Thromboembolism (VTE) involves strategies like:¹²

General prevention:

• Move around early: Walking soon after surgery or inactivity helps prevent clots
• Compression stockings: Improve blood flow and reduce clot risk
• Leg compression devices: Machines that gently squeeze the legs to improve circulation

Medications to prevent clots:

• Low-molecular-weight heparin (LMWH): A common blood thinner for high-risk individuals
• Warfarin: Another blood thinner that requires regular monitoring
• New Anticoagulants: Pills that prevent clotting without frequent monitoring

Lifestyle and prevention:

• Stay active, wear compression stockings, and drink plenty of water
• Avoid smoking and sitting for long periods

Special considerations:

• Pregnancy: Women with clotting disorders may need LMWH during pregnancy
• After birth: Blood thinners may be required for at least 6 weeks postpartum
• Antiphospholipid syndrome: Women with this condition and past pregnancy losses may need heparin and aspirin

Summary

Venous thromboembolism (VTE) is a serious condition that can lead to deep vein thrombosis (DVT) or pulmonary embolism (PE), especially in people with thrombophilia. Understanding the risk factors such as genetics, lifestyle, and medical conditions helps in prevention and treatment. Early movement, compression stockings, and blood thinners can reduce the risk. Proper diagnosis through blood tests and imaging is crucial for timely treatment. Managing VTE with lifestyle changes and medications can prevent complications. With awareness and adequate care, individuals at risk can take steps to protect their health and reduce the chance of dangerous blood clots.