Thrombosis

What is Thrombosis?

Thrombosis refers to the development of blood clots within our body’s blood vessels, either in our arteries or veins, which can hinder the normal flow of blood. The free movement of blood relies on a delicate balance between various components of blood like cells, platelets, proteins in the plasma, clotting factors, inflammatory factors, and the lining of the vessel itself. When this balance is disrupted, it can lead to an increased risk of developing a blood clot or various disorders related to blood clotting.

Some patients, owing to certain health conditions, may be at a higher risk of both, developing a clot and bleeding (e.g. with conditions like disseminated intravascular coagulation or cancers). Therefore, diagnosing and managing thrombosis can be complex. Thrombosis can occur in any organ system, and its symptoms may differ depending on the patient’s pre-existing health conditions and other risk factors.

When deciding on the treatment plan, doctors need to consider whether the clot is in the veins or arteries, the severity and duration of the condition, and whether it’s the patient’s first episode or a recurring condition. Other influencing factors include the patient’s family history, whether they smoke, and the stability of their blood circulation. The use and duration of blood-thinning medication or anti clotting drugs rely on a careful assessment of these factors.

In some cases, it might be beneficial to run comprehensive tests to understand inherited or acquired conditions that might result in a higher risk for thrombosis, although this decision can be controversial and typically involves the opinion of a blood disorder specialist or hematologist.

Thrombosis, in both veins and arteries, form the most common reasons for death in developed countries. Conditions like heart attacks and strokes, caused by blood clots, result in most thrombosis-related deaths in the United States. It’s essential for healthcare providers to understand how thrombosis occurs and the factors that can cause it; this can help them accurately diagnose, investigate, and manage this condition.

However, certain specific conditions, like acquired antiphospholipid syndrome (APS) or heparin-induced thrombocytopenia and thrombosis (HITT), can make diagnosing and treatment decisions more complicated. As such, these condition-specific details and managing aspects often fall outside of general understanding and require detailed studies or guidelines from specialized medical organizations.

The guidance is typically centered around understanding the basic functioning of thrombosis in veins and arteries, establishing the risk factors, the investigative procedures needed, and the management strategies for both venous and arterial thrombosis.

What Causes Thrombosis?

Thrombosis is the medical term for a blood clot that forms inside a blood vessel. This could occur due to a combination of several factors, known as “Virchow’s triad.” These factors includes damage to the inside lining of a blood vessel, a higher tendency of your blood to clot (also known as a hypercoagulable state), and blood flow that’s slower than normal.

Damage to the blood vessel lining can have various causes. It can happen directly, such as when a catheter is inserted or due to an injury, or indirectly, such as due to inflammation or changes to the cell structure.

A hypercoagulable state means there’s a higher likelihood for blood clots to form. This could be due to alterations in the blood clotting system, including changes caused by inflammation, thickened blood, or various proteins or factors in your blood that promote clotting.

This heightened tendency to form clots can either be inherited or acquired. Some people are born with a higher risk because of certain genetic mutations, while others may acquire this risk due to certain medications, underlying medical conditions, or lifestyle factors such as unhealthy diet, sedentary lifestyle, and smoking. Certain health conditions like cancer, obesity, and autoimmune disorders can also increase the risk of developing clots.

The third factor, blood stasis, refers to slowed or stagnant blood flow, which can occur due to immobilization (like being bed-bound), being pregnant, or having a previous blood clot. Extended periods of inactivity, as experienced during long flights or car rides, can also contribute to blood stasis.

Vein clots often start with damage to the blood vessel’s inner lining, while artery clots usually start with a buildup of fatty deposits in the arteries (atherosclerosis). Both types of clots can have similar risk factors like older age, obesity, smoking, constant inflammation, and metabolic syndrome. When clotting occurs, doctors will want to know whether the clot was provoked (meaning it has a known cause, like surgery or a broken bone) or unprovoked (meaning it doesn’t have a specific cause). The location and extent of the clot can also impact the treatment approach.

Venous blood clots usually appear as deep vein thromboses (DVTs) or pulmonary embolisms (PEs). These terms reflect where the clot is located: A DVT is a clot in a deep vein of the leg or arm, and a PE is a clot that traveled to the lungs. If a clot develops in less common areas like the brain’s veins or the veins of the eye, other diagnoses or underlying conditions should be considered.

Artery clots can lead to strokes, heart attacks, or diseases affecting the leg arteries. Other less common locations include the kidney, intestine, or eye arteries. Once a clot has occurred, doctors will focus on preventing future clots. This may involve lifestyle changes, controlling other health conditions, and medication.

Finally, age is also a major contributing factor to the development of clotting disorders. Studies have found that older individuals tend to have higher production of clot-promoting factors.

Risk Factors and Frequency for Thrombosis

Thrombosis, or blood clotting, can vary greatly. Factors like whether it’s in the veins or arteries, if it’s the first occurrence or a repeat, or whether it’s caused by something specific can change the rates we see in populations. For venous thromboembolism (VTE), meaning a clot in a vein, we see differing rates across age groups. It’s rarer in children and more common in older individuals. People of European origins more frequently face venous thrombosis as compared to non-Europeans.

Cancer patients also have a higher risk, four to seven times greater, of getting VTE, especially within the first few months after diagnosis. A system called the Ottawa score has been set up to predict the risk of recurrent VTE in cancer patients during the first six months of clot-preventing therapy, taking into account factors like sex, cancer type and stage, and history of VTE.

Pregnancy is a time when there’s especially high risk for thrombosis, with a 5-10 times greater risk due to increased clotting elements in the blood and other pregnancy-related factors. Having a clotting disorder can multiply this risk, and blood clots in the brain are rather common in this group. A condition affecting mainly women is APS, which occurs around 50 times per 100,000 people, where the ratio of female to male is around 5:1.

• The frequency of thrombosis, or blood clotting, changes based on a variety of factors such as where it’s happening, if it’s the first incident or a follow-up, and the reason behind it.
• Annual rates of venous thromboembolism (blood clots in veins) range from 1 per 100,000 children to 1 per 100 adults.
• People with European ancestry tend to have a higher rate of blood clots in veins compared to non-Europeans.
• Cancer patients face a risk of venous thrombosis that’s four to seven times higher than non-cancer patients, particularly within the first few months after a cancer diagnosis.
• The Ottawa score helps predict the risk of blood clots recurring in patients with cancer during the first 6 months of treatment, considering sex, type and stage of cancer, and history of blood clots.
• During pregnancy, the risk of blood clotting can increase 5-10 times due to pregnancy-related changes in the body.
• A blood clotting disorder can increase this risk even further, with blood clots in the brain being particularly common in pregnant women.
• APS, a condition mainly found in women, affects about 50 out of 100,000 people, with a female to male ratio of approximately 5:1.

Signs and Symptoms of Thrombosis

Thrombosis, or the formation of a blood clot, can occur in various areas of the body, each presenting with different signs and symptoms. For instance, deep vein thrombosis (DVT) commonly causes swelling, pain, warmth, and redness in the affected limb. The pain is usually described as ‘crampy,’ and there could be a loss of limb motion, difficulty walking, or pain spreading to other areas like the groin. Additionally, acute pulmonary embolism (PE), a condition where the clot travels to the lungs, may present with chest pain, breathlessness, fatigue, back pain, fainting, and in severe cases, it can even lead to death. Patients with acute PE may also show signs like a fast heart rate, rapid breathing, fever, and low oxygen levels in the blood.

Arterial thrombosis usually impacts the heart or brain. If the clot forms in the coronary arteries of the heart, it could result in intense left-sided chest pain that feels like crushing, along with pain spreading to the left arm or jaw. On the other hand, a clot in one of the cerebral arteries in the brain can lead to symptoms such as sudden weakness on one side, headache, confusion, vision changes, slurred speech, difficulty swallowing, numbness, difficulty walking, or even paralysis of one or more limbs.

Testing for Thrombosis

When you go to the hospital with signs of a possible blood clot, whether in the veins (venous thrombosis) or arteries (arterial thrombosis), the doctor will evaluate you differently depending on where they suspect the blood clot is.

For a suspected venous blood clot, doctors use what is known as modified Wells’ criteria, which assesses the likelihood of the blood clot being present. If these criteria suggest a high possibility of a clot, a test called serum D-dimer is done. D-dimer is a substance found in the blood after a clot has been broken down by the body. A high level of this substance can suggest a clot, but it could also be due to other conditions such as pregnancy, cancer, recent surgery, or an infection. If the D-dimer test is negative, it helps doctors rule out a blood clot and avoid unnecessary further testing or treatment.

However, if the doctor strongly believes you have a venous clot, they will go for imaging tests like CT angiography or V/Q scan, irrespective of the D-dimer levels. These imaging tests give them a better idea of what’s going on in your body. The V/Q scan is sometimes preferred over CT angiography to avoid the potential side effects of CT contrast in people with kidney problems. However, not all hospitals have the ability to perform or analyze V/Q scans so CT angiography is often used.

It is also important to figure out the type and history of the blood clot. Knowing if the clot came suddenly or if you’ve had many before, or whether it was provoked by something specific, guides how the condition is handled. Doctors also consider family history of blood clots or pregnancy issues as these could suggest an increased risk of clot formation.

Testing for a clot-prone state (thrombophilia) is only done if it would change the treatment course. For example, in provoked blood clots, the treatment would be the same whether you have thrombophilia or not, so testing is not necessary – so long as there are no contraindications to long-term anticoagulation treatment, it would be suggested.

Tests to assess clot-prone states may include checking for specific substances in the blood like proteins C and S, antithrombin III, or for certain gene changes associated with clotting disorders. Sometimes, these tests may not be accurate in the acute phase of a blood clot or when on anticoagulation therapy. Therefore, it is usually suggested to wait until 3 months after anticoagulation therapy has ceased to perform the tests.

Cancer can also cause both venous and arterial blood clots. However, extensive cancer examinations are generally not recommended unless other signs indicate a need for such tests. Sometimes, further evaluation for hidden cancer may be required, especially for those over the age of 50 with unprovoked thrombosis.

Arterial blood clots are usually caused by a condition known as atherosclerosis, a hardening and narrowing of the arteries. Diagnostic imaging tests like CT angiography or magnetic resonance angiography are used for these cases. If a heart attack has occurred, a procedure called cardiac catheterization is usually performed.

The therapy for arterial blood clots depends on where the clot is and the patient’s overall health. However, medication to inhibit platelet function is generally recommended. In some cases, treatment with another antiplatelet medication or a minimal dose of anticoagulation may also be needed. Some new medications are also being studied for use in arterial clots.

Treatment Options for Thrombosis

The treatment for blood clots in arteries and veins is different. For blood clots in veins, doctors usually use medicines that thin the blood and slow down its ability to form clots (anticoagulants). For blood clots in arteries, doctors primarily use medicines to stop platelets (small blood cells that help in blood clotting) from clumping together (antiplatelet agents). There are many different combinations of these treatments.

Specialized doctors such as lung doctors (pulmonologists), heart doctors (cardiologists), brain doctors (neurologists), and blood doctors (hematologists) may need to be consulted in certain cases. Society guidelines, from organizations like the American Society of Chest Physicians, American Heart Association, and American Society of Hematology, can provide more specific recommendations based on the exact case and patient’s condition.

Venous thromboembolism, or VTE, is a blood clot in the vein which can cause complications. Its treatment depends on whether the clot has been provoked or unprovoked. Causes for a provoked VTE include reversible or modifiable factors, such as recent surgery, trauma, infection, pregnancy, obesity, use of birth control pills, prolonged immobility, heavy smoking, or underlying cancer. An unprovoked VTE occurs without any clear provoking factor. The treatment of VTE unfolds in three stages: initial, chronic, and extended, and the strategy can vary depending on the specifics of each case.

Guidelines now suggest the use of direct oral anticoagulants (DOACs) over vitamin K antagonists, like warfarin, for most VTE conditions. DOACs include dabigatran, apixaban, edoxaban, and rivaroxaban. These medications directly target certain factors in blood clotting. They’re often preferred because they’re easier to use, carry fewer risks of bleeding and have proven benefits. However, DOACs have to be used with caution in patients with heart diseases and specific disorders where they may worsen the conditions. The main barriers to using DOACs are availability, cost, and patient’s kidney function.

For immediate treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients, anticoagulants like heparin are used initially, followed by oral anticoagulants like warfarin or DOACs for the long term. The duration for which these are given depends on factors such as severity, cause, and recurrence of the clot. Patients with active cancer as a risk factor for blood clots should typically continue this therapy for at least 6 months.

Monitoring the effectiveness and adjusting the dose of these drugs is essential. Heparin can be monitored using a test called partial thromboplastin time (PTT). For warfarin, a test called PT/INR is used to keep the dosage within the effective range. For DOACs, there is no routine blood monitoring required, but taking the medication consistently is essential for its effectiveness.

For hospitalized patients, the American Society of Hematology recommends using a low dose of heparin (UFH or LMWH). If blood thinners can’t be used, or if there’s a high risk of bleeding, mechanical methods like intermittent compression devices and elastic compression stockings, which stimulate blood flow in the legs, can be used.

Beside medicines, endovascular treatment, a minimally invasive procedure that treats clot-related disorders inside the blood vessels, is also used to manage clots. The use of inferior vena cava (IVC) filters, a small device that stops clots from travelling to the lungs, remains controversial and should only be used in certain cases. A detailed analysis of various options keeping in mind the risk and benefits is the key to the selection of these specialized intervention modalities and consultation with a specialist is strongly advised.

What else can Thrombosis be?

When doctors are trying to diagnose a health condition like a thrombosis, which refers to clot formation in a specific location that narrows the vessels, they usually also consider the possibility of an embolism. This is when a clot moves from its original location to somewhere else in the body. For example, in patients who have Deep Vein Thrombosis (DVT), the clot could shift to the lungs, which can result in a Pulmonary Embolism (PE).

It’s crucial to also think about septic emboli, especially in patients who are at risk of a widespread infection, have a history of IV drug use, or are suspected or confirmed to have bacterial endocarditis, a type of heart infection. Another condition that could cause similar symptoms, especially in the arms or legs, is chronic peripheral vascular disease. If doctors believe that this might be the problem, they typically seek a specialist opinion such as from a vascular surgeon.

What to expect with Thrombosis

The outlook for individuals diagnosed with thrombosis, or blood clots, can differ based on the type, location, severity, and the presence of risk factors that could aggravate the condition, as well as a person’s overall health. In addition, if someone has already had one episode of thrombosis, they are more likely to experience it again.

There is a particularly higher risk for recurrence in patients who have had venous thromboembolism (VTE), a condition where a blood clot forms in the deep veins of the body, especially if they have ongoing risk factors. Studies suggest that up to 25% of patients who have experienced this type of blood clot may have it recur within 10 years. This risk is especially high if they have multiple risk factors or an inherited or acquired tendency to form blood clots, known as thrombophilia.

It’s estimated that about 300,000 deaths happen each year in the European Union due to VTE. In the U.S., heart disease remains the most common cause of death. However, individuals with cerebrovascular disease, a group of conditions that affect the flow of blood to the brain, have mortality rates as high as 20% within the first month after suffering a stroke. Unfortunately, up to 30% of the people who survive a stroke could live with permanent disabilities.

As a result, preventing blood clots in both veins and arteries is crucial and understanding the lifestyle changes and the controllable risk factors can be beneficial for patients. This can give them the tools they need to manage their health better.

Possible Complications When Diagnosed with Thrombosis

If not managed correctly from the start, thrombosis can lead to problems. One serious, well-researched issue is post-thrombotic syndrome, a side effect of DVT (Deep Vein Thrombosis). Studies show that 20 to 50% of people with DVT may develop this syndrome within 1 to 2 years. The syndrome is more likely to develop in those with repeated DVT at the same location, people who are overweight, and those not taking their blood thinning medication correctly. Symptoms usually include chronic pain, a heavy feeling, cramps, and swelling worsened by exercise and eased by rest. Research suggests that wearing elastic compression stockings could prevent this syndrome.

Pulmonary hypertension is another problem that may occur due to chronic blood clots blocking the blood vessels in the lungs. Between 0.1% and 9% of people who have had a PE (Pulmonary Embolism) end up with this condition. Unlike other types of pulmonary hypertension, the type resulting from blood clots can be cured via a procedure to remove the clot.

Yet another serious problem related to thrombosis is unplanned bleeding (both inside and outside the brain), which can come as a result of treatment with high-dose blood thinning or antiplatelet medication. Bleeding in the brain can be particularly harmful and even deadly. For patients on warfarin, a type of vitamin K antagonist, the death rate from brain bleeding could be as high as 50%. Patients treated with blood thinning medications due to VTE (Venous Thromboembolism) face a risk of major bleeding of 7.2 events per 100 person-years, a risk of fatal bleeding of 1.31 per 100 person-years, and a fatality rate of 13.4% due to major bleeding. It’s crucial to evaluate the risk of bleeding from blood thinning or antiplatelet medication, and doctors should counsel their patients about this risk and how to avoid risky situations that could lead to bleeding (such as contact sports). Specifically, those at a particularly high risk of bleeding complications include older adults, those with uncontrolled high blood pressure, those taking antiplatelet medication alongside blood thinners, and those taking warfarin.

Complications:

• Post-thrombotic Syndrome
• Pulmonary Hypertension
• Development of chronic blood clots
• Unplanned bleeding
• Bleeding from the brain with potentially severe and lethal results
• Potential fatal bleeding

Preventing Thrombosis

The reasons for formation of blood clots in veins and arteries (known as venous and arterial thrombosis, respectively) can be many and depend on the person’s circumstances or condition. There are certain factors in your lifestyle or health that you can change to reduce the likelihood of developing these clots. You can reduce your risk by adopting healthy habits and actions, which your healthcare provider will guide you on.

People with higher likelihood of blood clotting — for example, those who are taking estrogen (a hormone), pregnant women, or individuals with severe obesity — should be aware of their increased risk. It’s important that you avoid staying still for long periods and make a habit of stretching often. Wearing elastic compression stockings may help. Quitting smoking is highly recommended, as it contributes to better overall health.

If you are taking blood-thinning medicine (aka anticoagulants) or antiplatelet therapy, which are used to prevent blood clots, it’s important to know the associated risks, including serious bleeding. Precautions to prevent falling is advised when you’re on these medications, so you should do everything you can to prevent accidents and injuries that could potentially cause you to bleed.