Thrombosis (blood clots) Related to Factor V Leiden
One in four people worldwide are dying from conditions caused by blood clots also known as a thrombosis.
The CDC reports that up to 900,000 people in the United States alone are affected by blood clots each year. About 100,000 of those people will die, which is greater than the total number of people who lose their lives each year to AIDS, breast cancer, and motor vehicle crashes combined.
According to the American Heart Association, pulmonary embolism is the most common preventable cause of death among hospital patients in the United States, and yet venous thromboembolism in general – and pulmonary embolism in particular – is often overlooked as a major public health problem.
The potential public health benefit of preventing VTE is considerable. Data from randomized trials involving general surgical patients suggest that adequate prevention measures in high-risk patients can prevent VTE in one of 10 patients – and save the life of about one of 200 patients.
What is Thrombosis
Thrombosis is the formation of a blood clot in a blood vessel. The vessel may be any vein or artery. A blood clot in a vein is called a venous thrombosis or VTE. A blood clot in an artery is called an arterial thrombosis. The clot itself is termed a thrombus.
Once formed, a clot can slow or block normal blood flow and even break loose and travel to an organ. A clot that travels through the circulatory system is called an embolism.
Thrombosis is the cause behind the top three cardiovascular killers today:
- Heart attack – a blood clot in an artery in the heart
- Stroke – a blood clot in an artery in the brain
- Venous thromboembolism – a blood clot in a vein.. the most fatal is a blood clot in the lung known as a pulmonary embolism
Sadly, many times these thrombosis are preventable.
Arterial Thrombosis vs. Venous Thrombosis
There are two main types of blood clots depending on whether the clot develops in a vein or an artery:
- Venous thrombosis is when the blood clot blocks a vein. Veins carry blood from the body back into the heart.
- Arterial thrombosis is when the blood clot blocks an artery. Arteries carry oxygen-rich blood away from the heart to the body.
Venous and arterial thrombosis are variations of similar pathologic mechanisms and both are influenced by acquired or inherited risk factors.
Arterial Thromboembolism
Arterial thrombosis is a blood clot that develops in an artery. It’s dangerous as it can obstruct or stop the flow of blood to major organs, such as the heart or brain. The blockage starves tissues of blood and oxygen. This can result in damage or tissue death known as necrosis.
If a blood clot blocks the arteries leading to part of the heart muscle, it will cause a heart attack. If it blocks an artery in the brain, it will cause a stroke. Less common sites include the kidneys, intestines, and eyes.
To date research studies are finding that having Factor V Leiden does not appear to increase the chances of developing a heart attack or stroke.
Venous Thromboembolism
Almost all thrombosis related to Factor V Leiden present as a venous thrombosis.
Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. It is the third leading vascular diagnosis after heart attack and stroke, affecting between 300,000 to 600,000 Americans each year.
The two most common types of venous thrombosis are a deep vein thrombosis (DVT) and a pulmonary embolism (PE).
Deep vein thrombosis (DVT) is a medical condition that occurs when a blood clot forms in a deep vein. These clots usually develop in the lower leg, thigh, or pelvis, but they can also occur in the arm.
A pulmonary embolism (PE) occurs when a clot breaks loose and travels through the bloodstream to the lungs.
There are many different types of venous thrombosis:
- Deep Vein Thrombosis (DVT)
- Pulmonary Embolism (PE)
- Superficial Venous Thrombosis
- Cerebral Venous Sinus Thrombosis (CVST)
- Dural Sinus Thrombosis (DST)
- Hepatic Vein Thrombosis of the Liver also known as Budd-Chiari Syndrome
- Femoral Vein Thrombosis
- Paget-Schroetter Syndrome (PSS)
- Superior Vena Cava Thrombosis
- Jugular Vein Thrombosis
- Cavernous Sinus Thrombosis of the Sinuses
- Retinal Vein Occlusion of the Eye
- May-Thurner Syndrome
- Portal Vein Thrombosis of the Liver
- Renal Vein Thrombosis of the Kidneys
A venous thrombosis can be categorized as provoked or unprovoked.
Provoked VTE – A provoked VTE refers to a thrombotic event that has been caused by an environmental or acquired known risk factor for VTE. Provoked events may be divided into transient or persistent causes.
- Transient Provoked VTE – A transient variable is expected to resolve after the VTE event, and this has a bearing on treatment and prognosis for recurrence. Examples of transient provoked risk factors include bed rest for more than 3 days, immobility, estrogen therapy, trauma or surgery, pregnancy, or a hip or leg injury.
- Persistent Provoked VTE – Active cancer, congestive heart failure (CHF), obesity, and varicose veins are examples of persistent provoked risk factors.
Unprovoked VTE – An unprovoked VTE refers to a thrombotic event that is not associated with an environmental risk factor. Examples of nonenvironmental risk factors are hereditary thrombophilia like Factor V Leiden, male gender, or older age.
If VTE is provoked by a transient risk factor, there is a lower risk of recurrence after stopping therapy.
Recurrent Venous Thrombosis
Approximately 30% of individuals with an incident of VTE develop recurrent thrombosis within the subsequent 8 years. There are conflicting data on the risk of recurrent VTE associated with Factor V Leiden heterozygosity. The current evidence suggests that it has at most a modest effect on recurrence risk after initial treatment of a first VTE. Several prospective cohort studies of unselected individuals with a first VTE, did not find an increased risk for recurrence in Factor V Leiden heterozygotes. Recently reported follow-up of participants in the Leiden Thrombophilia study also found no increase in recurrence risk. A meta-analysis including 3,104 individuals with a first VTE concluded that a heterozygous mutation is associated with a significantly increased risk for recurrent VTE after a first event with an odds ratio of 1.4. Two systematic reviews found a similar modest but significant increase in recurrence risk (pooled odds ratio = 1.56 and 1.45, respectively). Several studies showed that the reduction in risk during oral anticoagulation is similar in individuals with and without the Factor V Leiden mutation.
The risk for recurrent VTE in Factor V Leiden homozygotes is not well defined but presumed to be higher than in heterozygotes. Prospective follow-up of the Leiden Thrombophilia study reported a 5-year cumulative recurrence rate of 12.5% in a small group of homozygotes not receiving long-term anticoagulation. A systematic review found a 2- to 3-fold increased risk for recurrent VTE in Factor V Leiden homozygotes. Individuals doubly heterozygous for both Factor V Leiden and the prothrombin 20210G>A mutation have a 3- to 9-fold higher risk for recurrence than those with neither mutation and a 3-fold higher risk than individuals heterozygous for Factor V Leiden alone. However, not all studies found a high risk for recurrence in homozygotes and double heterozygotes. In a recent study of thrombophilic families, individuals homozygous for Factor V Leiden or doubly heterozygous for Factor V Leiden and the prothrombin 20210G>A mutations did not have an increased risk for recurrence, even when the analysis was restricted to those with a first idiopathic VTE. Risk estimates were limited by the small number of homozygotes and double heterozygotes included in these studies.
The risk for recurrent VTE is 4- to 5-fold higher in Factor V Leiden heterozygotes with hyperhomocysteinemia than in individuals with a Factor V Leiden allele alone. In contrast, Factor V Leiden heterozygotes with high Factor VIII levels did not have a higher risk for recurrent VTE than individuals without thrombophilia.
Please reference the “Factor V Leiden Research and Resource Library” for more information on each of these types of venous blood clots.