Causes and Treatment of Deep Vein Thrombosis and Blood Clots

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• Blood Clot Causes Overview
• Provoked vs Unprovoked Clots
• Genetic Risk Factors
• Cancer Hypercoagulable Link
• Blood Clot Treatment Options
• Anticoagulation Duration
• Full Transcript

Blood Clot Causes Overview

Blood clots, or thrombosis, form when blood coagulates abnormally inside a blood vessel. Dr. Aric Parnes, MD, a hematology expert, explains that this process is the opposite of a bleeding disorder. The most common location for a problematic clot is in the deep veins of the legs, a condition known as deep venous thrombosis (DVT).

These clots are dangerous because they can break free and travel to the lungs. This causes a pulmonary embolism, a life-threatening condition with a mortality rate of approximately 30%. Dr. Anton Titov, MD, highlights the importance of understanding the root causes to guide effective treatment and prevention strategies.

Provoked vs Unprovoked Clots

Hematologists categorize blood clots as either provoked or unprovoked. Dr. Aric Parnes, MD, defines provoked clots as those with a clear triggering event. Common provokers include major surgery, bone fractures, or extended periods of immobility from hospitalization or long-haul travel.

Unprovoked clots, also called idiopathic thrombosis, lack an obvious cause. This classification is crucial because it directly influences treatment decisions. An unprovoked clot often signals an underlying, persistent hypercoagulable state that may require long-term management.

Genetic Risk Factors

Several inherited genetic mutations significantly increase a person's risk of developing venous thrombosis. Dr. Aric Parnes, MD, details the most common ones. Factor V Leiden (Factor 5 Leiden) is a gene polymorphism prevalent in individuals of Northern European descent.

Another key mutation is the prothrombin 20210 gene mutation, also known as Factor II Mutation. Deficiencies in natural anticoagulant proteins like protein C, protein S, and antithrombin III are also well-established genetic causes of a hypercoagulable state. Dr. Anton Titov, MD, notes that testing for these factors is typically reserved for patients with a personal or strong family history of clots.

Cancer Hypercoagulable Link

A critical cause of unprovoked blood clots is cancer. Dr. Aric Parnes, MD, emphasizes that a hypercoagulable state is a frequent complication of malignancy. Cancer cells can activate the clotting system, making blood more prone to coagulation.

Alarmingly, a deep venous thrombosis can be the first sign of an undiagnosed cancer. Dr. Aric Parnes, MD, states that roughly 20% of patients presenting with a new blood clot in a vein are found to have cancer. This statistic makes a thorough evaluation for malignancy essential in cases of unexplained thrombosis.

Blood Clot Treatment Options

Treating blood clots requires anticoagulant medications, commonly known as blood thinners. Dr. Aric Parnes, MD, outlines the available options. Classic anticoagulants include warfarin (Coumadin), which is often bridged with an injectable heparin initially.

Modern treatment has been revolutionized by direct oral anticoagulants (DOACs). These newer medications include dabigatran (Pradaxa), a direct thrombin (Factor II) inhibitor, and rivaroxaban (Xarelto) and apixaban (Eliquis), which are Factor Xa inhibitors. Dr. Anton Titov, MD, underscores that choosing the right agent is a complex decision best made with a hematology specialist.

Anticoagulation Duration

Determining how long a patient must stay on anticoagulation therapy is a major clinical decision. Dr. Aric Parnes, MD, explains that the cause of the clot dictates the duration. For a provoked clot, such as one after surgery, a short course of 3 months is often sufficient.

The situation is different for unprovoked or idiopathic clots. These events suggest a permanent underlying risk. Therefore, patients with unprovoked deep venous thrombosis or pulmonary embolism may require lifelong anticoagulation therapy. Dr. Aric Parnes, MD, confirms this is a challenging decision that requires careful discussion between the patient and their hematologist.

Full Transcript

Dr. Anton Titov, MD: Blood clots causes include hypercoagulable state in cancer. Twenty percent of patients with newly diagnosed blood clots in veins have cancer. Deep venous thrombosis is the most common blood clot disorder.

What are provoked blood clots? What are unprovoked blood clots? What is Factor V Leiden, protein C and protein S deficiency? How long should anticoagulation last to prevent pulmonary embolism? A top hematology expert explains causes of blood clots and DVT.

Deep venous thrombosis is a frequent sign of hypercoagulable state.

Venous thromboembolism can be caused by unprovoked blood clots and provoked blood clots. Provoked clots are often caused by surgery or a period of immobility. Blood moves slower through the veins and can form a thrombus, or blood clot.

Causes of unprovoked blood clots include cancer, genetic mutations, and birth control pills. Hypercoagulable state could be a first sign of cancer in the body. Blood clots can separate from leg veins and travel to lungs to cause a pulmonary embolism.

Blood clots causes are important to find out. Deep venous thrombosis is just one frequent cause of increased blood clotting.

Dr. Anton Titov, MD: Medical second opinion helps to make sure diagnosis is correct and complete. It helps to choose the best treatment for deep venous thrombosis. A medical second opinion by an experienced hematologist can help identify a cause of unprovoked blood clots.

Dr. Aric Parnes, MD: Genetic mutations that increase risk for blood clot formation are Factor V Leiden thrombophilia, prothrombin 20210 gene mutation, Factor II mutation, protein C deficiency, and protein S deficiency. Women who smoke and take birth control pills with estrogens are at particularly high risk for venous thrombosis, including deep venous thrombosis in leg veins.

Treatment of blood clots requires medical second opinion by a hematologist. Classic anticoagulants like warfarin and new oral anticoagulants such as dabigatran and rivaroxaban are used to treat deep venous thrombosis.

Blood clots causes have to be found before treatment begins. Deep venous thrombosis signals presence of hypercoagulable state. Duration of anticoagulation depends on the cause of blood clot.

Provoked blood clots, such as those after surgery or fracture, require several months of anticoagulation. Unprovoked blood clots often require lifelong anticoagulation.

Dr. Anton Titov, MD: Blood clots sometimes form when they should not form. This is the opposite of bleeding disorders that we discussed previously. Blood clot causes and treatment is one of your clinical and research interests.

Deep venous thrombosis and other blood clotting disorders is a large problem. DVT, blood clots in leg veins, happen.

Dr. Aric Parnes, MD: Sometimes blood clots break off from the leg veins. Then blood clots can travel to lungs and cause pulmonary embolism. Pulmonary embolism has a 30% death rate.

Sometimes blood clots form in a coronary artery. Thrombosis causes myocardial infarction. Blood clots in brain veins cause cerebral venous thrombosis. It is called sagittal sinus thrombosis.

Dr. Anton Titov, MD: Could you please talk about causes of abnormal blood clot formation, thrombosis? How blood clots are diagnosed? What is the best treatment for thrombosis? How to treat deep vein thrombosis and its complications?

Dr. Aric Parnes, MD: We divide thrombosis into venous thrombosis or arterial thrombosis. Hematologist deals primarily with venous thrombosis. The arterial thrombosis is the realm of cardiologists. It causes myocardial infarction, heart attack.

Arterial thrombosis in brain causes strokes. This is in the realm of neurologists. Work of hematologist sometimes overlaps with the domain of cardiology and neurology.

My work primarily focuses on venous thrombosis, for example, clots in the legs. Blood clots can break off from leg veins and travel up to the lungs. This causes a pulmonary embolism.

Dr. Anton Titov, MD: Cancer can also cause blood clots. Deep venous thrombosis could be the first sign of cancer. Cancer also leads to hypercoagulable state, when blood has increased propensity to form clots. Twenty percent of patients with newly diagnosed blood clots in veins have cancer.

Dr. Aric Parnes, MD: That is correct. Blood clots in veins can often be a first sign of cancer in the body. This brings us to hypercoagulable state. It is increased risk of blood clotting.

What kind of patients get thrombosis? Cancer patients are certainly at risk of venous thrombosis. It forms often in deep leg veins. People sometimes cannot move well. Patients are in the hospital. They have increased risk of blood clot formation.

Patients with bone fractures are also at risk of thrombosis because they cannot be very active. Elderly patients are at risk of venous thrombosis for similar reasons. Risk of venous thromboembolism increases in obesity.

Pregnancy also leads to increased risk of deep vein thrombosis. This is because during pregnancy mobility decreases, venous blood circulation in legs worsens, and hormonal balance changes.

Recently we discovered genetic predispositions to venous thrombosis. Factor V Leiden is gene polymorphism common in patients of Northern European ancestry.

Dr. Anton Titov, MD: Factor V Leiden increases risk of deep venous thrombosis and pulmonary embolism and risk of miscarriage in pregnancy.

There is also the prothrombin gene mutation. Prothrombin 20210 gene mutation, Factor II mutation. It also can predispose patients to blood clots in legs and to pulmonary embolism. Risk of baby miscarriage is also increased in pregnant women.

There are also other mutations in clotting cascade that increase risk of venous thromboembolism.

Dr. Aric Parnes, MD: Other genetic cause of increased risk for venous thrombosis is protein C deficiency. Protein S deficiency also causes increased clotting of blood. Antithrombin III deficiency is another genetic mutation that predisposes to deep venous thrombosis.

Most of the time we don't know what causes blood clots to form. We call these unexplained blood clots unprovoked clots. This includes unprovoked deep venous thrombosis.

Testing for cancer is wise in patients with unexplained and unprovoked blood clots. Provoked blood clots can happen after surgical operation or after period of immobility. We also know that cancer treatment can sometimes cause blood clots to form in veins.

Dr. Anton Titov, MD: Long-haul airplane travel also increases risk of venous thrombosis and pulmonary embolism. Women may take birth control pills. They are at increased risk for blood clot formation.

Female hormone estrogen is part of birth control pills. Estrogen increases thrombosis risks.

Dr. Aric Parnes, MD: That's right. One of the most important risks of birth control pills is blood clots. Anybody with known hypercoagulable state should not get estrogen supplementation.

But birth control pills are a very common medication. Sometimes a woman takes birth control pills. Then she develops a blood clot. It is often deep venous thrombosis in legs. We can recognize that risk and stop the medication.

Dr. Anton Titov, MD: Is smoking an additional risk factor for venous thrombosis in women who are on birth control pills?

Dr. Aric Parnes, MD: Yes, it is. We can think about risk for blood clot formation as concept of threshold. A person can accumulate different risk factors for increased blood clotting. Risk factors could be smoking, oral contraception, obesity.

Eventually these risk factors add up. Then the threshold for venous thrombus formation is crossed over. Sometimes we see several risk factors for thrombosis. We try to minimize them.

For example, a woman might have a known protein C deficiency. She could be diagnosed because her mother had a blood clot and genetic tests were done on the daughter. In this situation I will never prescribe oral contraceptive pills to such woman with protein C deficiency.

Dr. Anton Titov, MD: There is a test for protein C deficiency?

Dr. Aric Parnes, MD: Yes, there is. We typically don't test for these causes of thrombosis risks. We do these tests when there is a history of blood clots in the family.

We also do tests to find causes of venous thrombosis in patients who are already diagnosed with a blood clot. Treatment of deep vein thrombosis and other hypercoagulable states is very similar.

We prescribe blood thinners. Warfarin and heparin are classic anticoagulant medications. We also now have many new oral anticoagulants to choose from. We now target clotting Factor II and Factor X.

Dabigatran is a Factor 2 inhibitor. Rivaroxaban and apixaban are factor Xa inhibitors. The data about these new oral anticoagulants is still accumulating.

How long do we need to anticoagulate patients with blood clots? This issue is still in flux. The optimal duration of anticoagulation treatment is still debated.

Sometimes when I was training, patients with the blood clot in the leg would get anticoagulant medication for three to six months. Previously advice for patients with blood clot in the lungs was to receive 6 to 12 months of anticoagulation treatment.

Recent clinical trials showed that 3 months of anticoagulation treatment is good for all of these clots, deep venous thrombosis or pulmonary embolism. But this treatment duration advice is valid only if the cause of these blood clots is known.

To the contrary, some patients have an unprovoked blood clot when the cause of thrombosis is not known. This is idiopathic thrombosis event. Such patients can be permanently at risk for increased blood clotting. Therefore they might need anticoagulant therapy for the rest of their life.

An experienced hematologist should assess each situation carefully.

Dr. Anton Titov, MD: Lifelong anticoagulation treatment is a very big decision for any patient.

Dr. Aric Parnes, MD: Permanent anticoagulation therapy is a very hard decision. Most young patients do not like to hear that.

Dr. Anton Titov, MD: Video interview with top expert in hematology. Hypercoagulable state as first sign of cancer. Unprovoked clots and provoked blood clots.

Blood clots can be caused by cancer. This is hypercoagulable state. Twenty percent of people with newly diagnosed blood clots in veins have cancer. Deep venous thrombosis is the most common blood clot disorder.