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Blood Clot Formation (Thrombosis)
- What Is Blood Clot Formation (Thrombosis)?
- What Is a Clotting Disorder (Thrombophilia)?
- Incidence of Clotting in the Veins (Venous Thrombosis)
- Causes of Blood Clots
The term thrombosis describes the formation of a blood clot in a blood vessel. The blood vessel can be a vein (venous system) or an artery (arterial system). The symptoms that occur with a clot depend on where the clot occurs, the size of the clot, and whether the clot breaks off and travels to another part of the body (a process called embolization). For example, a blood clot in the leg can break off and travel to the lungs (called a pulmonary embolism) or travel to the brain (called an embolic stroke).
Clots in the veins mainly occur in the extremities, but they can also occur in the veins of internal organs such as the liver, spleen, or intestines. The most common types of clots in the veins are deep vein thrombosis (DVT) and pulmonary embolism (PE). Clots in the arteries can also affect a variety of organs including the brain (stroke), heart (myocardial infarction), or intestines (abdominal angina).
Thrombophilia is a term used to describe a group of conditions in which there is an increased tendency, often repeated and over an extended period of time, for excessive clotting. Inherited or acquired abnormalities of coagulation can increase an individual’s risk of developing a clot. These conditions are prothrombotic (ie, they promote clot formation) and are commonly known as clotting disorders or thrombophilia. For more detailed information on clotting disorders, click here. According to the US Centers for Disease Control and Prevention (CDC),1 between 5% and 8% of the US population has a clotting disorder. Inherited clotting disorders such as deficiencies in antithrombin, protein C or protein S lead to a lifelong increased risk of clots. Identifying an underlying clotting condition clearly has important implications for an individual’s life and medical care.
The risk of blood clots is higher in individuals who have several risk factors for clotting— for example, a person with an inherited clotting condition Factor V Leiden [FVL], protein S deficiency, protein C deficiency, or antithrombin deficiency) who also has other risk factors such as pregnancy, oral contraceptive use, or high levels of homocysteine or factor VIII is at a higher risk for developing a clot than an individual with an isolated or single risk factor.
The precise number of individuals affected by clotting in the veins (venous thrombosis) is unknown. According to the CDC, 300,000 to 600,000 people per year experience DVT or PE.1 Of those who experience a DVT, nearly one third develop postthrombotic syndrome. The symptoms of this chronic disabling condition include swelling, pain, discoloration, and scaling of the affected limb. For some individuals DVT becomes a chronic illness— about 30% of people who have a DVT are at risk of experiencing another clotting episode. It is important to note that many episodes of DVT are preventable and treatable if diagnosed accurately and early.
An estimated 60,000 – 100,000 Americans die of DVT/PE each year.1 Because fewer than 50% of the people with PE have symptoms, some studies suggest that the actual numbers of affected individuals may be much higher.2 Estimates of the number of people with PE are less reliable than those for DVT because many patients with PE are not diagnosed.
Incidence of Blood Clots in Pediatric Populations
Although blood clots are more common in adults, they also can occur in children. The annual incidence in pediatric populations is 0.07 to 0.14 per 10,000 children, or 5.3 per 10,000 pediatric hospital admissions, and 24 per 10,000 neonatal intensive care unit admissions. Newborns and babies younger than 1 year are at greatest risk for childhood clots. Children in neonatal and pediatric intensive care units and those with cancers are particularly at high risk. A second peak occurs in adolescence. Teenage girls have twice the rate of clots as teenage boys. This difference is related to the use of oral contraceptives and pregnancy. Even in the presence of inherited or acquired clotting risk factors, children are less likely than adults to develop clots because they have generally healthy blood vessels.
Clotting diseases without a known cause occur in less than 5% of children compared to approximately 40% of adults. Furthermore, most of the clotting events in children are “triggered,” meaning that children may develop several “temporary” risk factors associated with clotting disorders. Central venous catheters are an important risk factor for development of a clotting event in children, yet account for only a small percent of venous clots among adults. As in adults, children with cancer, trauma/surgery, and systemic lupus erythematosus (SLE) are at increased risk of developing a clot.
The most important inherited conditions contributing to development of clotting events in children include deficiencies of natural anticoagulants such as proteins C and S, and antithrombin. When considered individually, other inherited clotting disorders, such as the factor V Leiden mutation (also called activated protein C [APC] resistance) or the prothrombin 20210 mutation are less important risk factors in children.
The formation of blood clots in the veins is related to three abnormalities commonly known as “Virchow’s triad”. The processes of Virchow’s triad include the following:
- Damage to blood vessels
- Excessive clotting ability (hypercoagulability)
- Pooling of blood (stasis)
Maintaining normal blood flow involves careful coordination of the three main clotting processes— procoagulant (promotes clotting), anticoagulant (prevents clotting), and fibrinolytic (clot breakdown) systems. Over the past 30 years, our understanding of the mechanisms that lead to clotting and clotting disorders and their treatment has significantly improved.
Procoagulant clotting proteins are essential in the starting and progression of normal clot formation. The naturally occurring anticoagulant proteins are needed to regulate clotting once it has started. This clotting process keeps the clot at the area of injury by controlling the procoagulant system. Once a stable clot has formed and bleeding has been controlled, the fibrinolytic system removes the clot and restores the normal structure of the blood vessels.
In clotting diseases, the causes of clotting may be related to increased levels of procoagulants, decreased levels of natural anticoagulants, or defects in the fibrinolytic system. In addition, abnormalities in the blood vessels contribute to development of clots.
Inherited causes of blood clots are related to a genetic (inherited) tendency for clot formation that generally occur at a young age (for example, occurring before 40 or 45 years), with or without an apparent cause, and with a tendency to recur.
Table 1 provides a list of inherited causes of blood clots. For more detailed information on these conditions, click on the individual condition or visit the section on Inherited Causes of Blood Clots.
|Table 1. Inherited Causes of Blood Clots|
|Increased Levels of Procoagulants||Decreased Levels of Anticoagulants||Abnormal Fibrinolysis||Other Inherited Causes|
|Factor V Leiden mutation or activated protein C resistance*||Antithrombin||Plasminogen Deficiency||Paroxysmal Nocturnal Hemoglobinemia|
|Prothrombin 20210 mutation||Protein C||Decreased Levels of Tissue Plasminogen Activator (t-PA)|
|Hyperhomocysteinemia||Protein S||Increased Levels of Plasminogen Activator Inhibitor-1 (PAI-1)|
|FVIII, FIX, FXI, FVII, VWF||Thrombomodulin||Elevated Thrombin-Activatable Fibrinolysis Inhibitor (TAFI)|
|Heparin Cofactor II|
|Tissue Factor Pathway Inhibitor (TFPI)|
|*The Factor V Leiden mutation does not result in increased FV levels but a resistance to the anticoagulant action of activated protein C.|
Acquired Causes of Blood Clots
A variety of factors can contribute to acquired clotting conditions. These factors are summarized in Table 2. To learn more about specific acquired causes of clotting, click on the individual cause or visit the Acquired Causes of Blood Clots section of this website.
Table 2. Acquired Causes of Blood Clots
Want to Learn More?
- Signs and Symptoms of Blood Clots
- Diagnosis of Blood Clots
- Treatment of Blood Clots
- Inherited Causes of Blood Clots
- Acquired Causes of Blood Clots
- Special Considerations for People with Clotting Disorders
- What Can the IHTC Do for You?
- Clotting Disorders FAQs
- Centers for Disease Control and Prevention (CDC). Available at: http://www.cdc.gov/ncbddd/dvt/index.html.
- Heit, JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008;28:370-372.