Thrombosis is the formation of a
blood clotA thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...
(
thrombus; Greek: θρόμβος) inside a
blood vesselThe blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
, obstructing the flow of
bloodBlood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
through the
circulatory systemThe circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
. When a blood vessel is injured, the body uses platelets (thrombocytes) and
fibrinFibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
to form a blood clot to prevent blood loss. Alternatively, even when a blood vessel is not injured, blood clots may form in the body if the proper conditions present themselves. If the clotting is too severe and the clot breaks free, the traveling clot is now known as an
embolusAn embolus is any detached, itinerant intravascular mass carried by circulation, which is capable of clogging arterial capillary beds at a site distant from its point of origin.By contrast there are non-traveling blockages that develop locally from vascular trauma or...
.
Thromboembolism is the combination of thrombosis and its main complication,
embolismIn medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
.
When a thrombus occupies more than 75% of surface area of the
lumenA lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
of an artery, blood flow to the tissue supplied is reduced enough to cause symptoms because of decreased
oxygenOxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
(
hypoxiaHypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
) and accumulation of metabolic products like
lactic acidLactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
. More than 90% obstruction can result in
anoxiaThe term anoxia means a total decrease in the level of oxygen, an extreme form of hypoxia or "low oxygen". The terms anoxia and hypoxia are used in various contexts:* Anoxic waters* Anoxic event* Dead zone or hypoxic zones...
, the complete deprivation of oxygen, and
infarctionIn medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
, a mode of
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
death.
Causes
In classical terms, thrombosis is caused by abnormalities in one or more of the following (
Virchow's triadVirchow's triad describes the three broad categories of factors that are thought to contribute to thrombosis.*Hypercoagulability*Hemodynamic changes *Endothelial injury/dysfunction...
):
- The composition of the blood (hypercoagulability or thrombophilia)
- Quality of the vessel wall (endothelial cell injury)
- Nature of the blood flow (stasis, turbulence)
Hypercoagulability
Hypercoagulability is caused by, for example, genetic deficiencies or autoimmune disorders.
Endothelial cell injury
Causes of injury to the vessel's wall include trauma, surgery, infection or turbulent flow at bifurcations. The main mechanism is exposure of
tissue factorTissue factor, also called platelet tissue factor, factor III, thrombokinase, or CD142 is a protein present in subendothelial tissue, platelets, and leukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. An incorrect synonym is thromboplastin...
to the blood coagulation system.
Disturbed blood flow
Causes of disturbed blood flow include stagnation of blood flow past the point of injury, or
venous stasisVenous stasis, or venostasis, is a condition of slow blood flow in the veins, usually of the legs. A patient with venous stasis might be more vulnerable to the formation of blood clot, especially in the deep veins of the legs, called deep vein thrombosis .Causes include long periods of immobility...
which may occur in heart failure or after long periods of sedentary behavior— for example, sitting on a long airplane flight. Also,
atrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
, causes stagnant blood in the left atrium (LA) or left atrial appendage (LAA), and can lead to a thromboembolism. Cancers or malignancies such as leukemia may cause increased risk of thrombosis by e.g. external compression on a blood vessel or (more rarely) extension into the vasculature (for example, renal cell cancers extending into the renal veins). Also, treatments for cancer (radiation, chemotherapy) often cause additional hypercoagulability.
Classification
There are two distinct forms of thrombosis, each of which can be presented by several subtypes.
Venous thrombosis
Venous thrombosis is the formation of a thrombus (blood clot) within a
veinIn the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
. There are several diseases which can be classified under this category:
Deep vein thrombosis
Deep vein thrombosis (DVT) is the formation of a blood clot within a
deep veinDeep vein is a term used to describe a vein that is deep in the body. It is used to differentiate deep veins from veins which are close to the surface, also known as superficial veins....
. It most commonly affects leg veins, such as the
femoral veinIn the human body, the femoral vein is a blood vessel that accompanies the femoral artery in the femoral sheath. It begins at the adductor canal and is a continuation of the popliteal vein...
. Three factors are important in the formation of a blood clot within a deep vein—these are the rate of blood flow, the thickness of the blood and qualities of the vessel wall. Classical signs of DVT include
swellingIn medical parlance, swelling is the transient enlargement or protuberance in the body and may include tumors. According to cause, it may be congenital, traumatic, inflammatory, neoplastic or miscellaneous....
, pain and redness of the affected area.
Portal vein thrombosis
Portal vein thrombosis is a form of venous thrombosis affecting the
hepatic portal veinThe hepatic portal vein is not a true vein, because it does not conduct blood directly to the heart. It is a vessel in the abdominal cavity that drains blood from the gastrointestinal tract and spleen to capillary beds in the liver...
, which can lead to portal
hypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and reduction of the blood supply to the liver. It usually has a pathological cause such as
pancreatitisPancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
,
cirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
,
diverticulitisDiverticulitis is a common digestive disease particularly found in the large intestine. Diverticulitis develops from diverticulosis, which involves the formation of pouches on the outside of the colon...
or
cholangiocarcinomaCholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
.
Renal vein thrombosis
Renal vein thrombosis is the obstruction of the
renal veinThe renal veins are veins that drain the kidney. They connect the kidney to the inferior vena cava.It is usually singular to each kidney, except in the condition "multiple renal veins".It also divides into 2 divisions upon entering the kidney:...
by a thrombus. This tends to lead to reduced drainage from the kidney. Anticoagulation therapy is the treatment of choice.
Jugular vein thrombosis
Jugular vein thrombosis is a condition that may occur due to infection, intravenous drug use or malignancy. Jugular vein thrombosis can have a varying list of complications, including:
systemic sepsisSepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
,
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
, and
papilledemaPapilledema is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare....
. Though characterized by a sharp pain at the site of the vein, it can prove difficult to diagnose, because it can occur at random.
Budd-Chiari syndrome
Budd-Chiari syndrome is the blockage of the
hepatic veinIn human anatomy, the hepatic veins are the blood vessels that drain de-oxygenated blood from the liver and blood cleaned by the liver into the inferior vena cava....
or the
inferior vena cavaThe inferior vena cava , also known as the posterior vena cava, is the large vein that carries de-oxygenated blood from the lower half of the body into the right atrium of the heart....
. This form of thrombosis presents with
abdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
,
ascitesAscites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
and
hepatomegalyHepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
. Treatment varies between therapy and surgical intervention by the use of
shuntShunt may refer to:* Shunt - a hole or passage allowing fluid to move from one part of the body to another* Shunt - a device allowing electrical current to pass around a point in a circuit...
s.
Paget-Schroetter disease
Paget-Schroetter disease is the obstruction of an upper extremity vein (such as the
axillary veinIn human anatomy, the axillary vein is a large blood vessel that conveys blood from the lateral aspect of the thorax, axilla and upper limb toward the heart...
or
subclavian veinThe subclavian veins are two large veins, one on either side of the body. Their diameter is approximately that of the smallest finger.-Path:Each subclavian vein is a continuation of the axillary vein and runs from the outer border of the first rib to the medial border of anterior scalene muscle...
) by a thrombus. The condition usually comes to light after vigorous exercise and usually presents in younger, otherwise healthy people. Men are affected more than women.
Cerebral venous sinus thrombosis
Cerebral venous sinus thrombosis (CVST) is a rare form of
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
which results from the blockage of the
dural venous sinusesThe dural venous sinuses are venous channels found between layers of dura mater in the brain...
by a thrombus. Symptoms may include
headacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body and seizures. The diagnosis is usually made with a
CTX-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
or
MRI scanMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
. The majority of persons affected make a full recovery. The
mortality rateMortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
is 4.3%.
Arterial thrombosis
Arterial thrombosis is the formation of a thrombus within an
arteryArteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
. In most cases, arterial thrombosis follows rupture of
atheromaIn pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
, and is therefore referred to as
atherothrombosis.
Another common cause of arterial thrombosis is
atrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
, which causes disturbed blood flow. In addition, it is well known that the direct current
cardioversionCardioversion is a medical procedure by which an abnormally fast heart rate or cardiac arrhythmia is converted to a normal rhythm, using electricity or drugs. Synchronized electrical cardioversion uses a therapeutic dose of electric current to the heart, at a specific moment in the cardiac cycle...
of atrial fibrillation carries a great risk of thromboembolism, especially if persisting more than 48 hours. Thromboembolism strikes approximately 5% of cases not receiving anticoagulant therapy. The mechanism and pathogenesis of thromboembolism after cardioversion is not completely understood.
Arterial thrombosis can embolize and is a major cause of
arterial embolismArterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery and blocks the flow of blood, the major type of embolus being a blood clot...
, potentially causing
infarctionIn medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
of almost any organ in the body.
Stroke
A stroke is the rapid decline of brain function due to a disturbance in the supply of blood to the brain. This can be due to
ischemiaIn medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, thrombus,
embolusAn embolus is any detached, itinerant intravascular mass carried by circulation, which is capable of clogging arterial capillary beds at a site distant from its point of origin.By contrast there are non-traveling blockages that develop locally from vascular trauma or...
(a lodged particle) or hemorrhage (a bleed). In thrombotic stroke, a thrombus (blood clot) usually forms around atherosclerotic plaques. Since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower. Thrombotic stroke can be divided into two categories—large vessel disease and small vessel disease. The former affects vessels such as the internal carotids,
vertebralThe vertebral arteries are major arteries of the neck. They branch from the subclavian arteries and merge to form the single midline basilar artery in a complex called the vertebrobasilar system, which supplies blood to the posterior part of the circle of Willis and thus significant portions of the...
and the
circle of WillisThe Circle of Willis is a circle of arteries that supply blood to the brain...
. The latter can affect smaller vessels such as the branches of the circle of Willis.
Myocardial infarction
Myocardial infarction (MI) is caused by an infarct (death of tissue due to ischemia), often due to the obstruction of a coronary artery by a thrombus. MI can quickly become fatal if emergency medical treatment is not received promptly. If diagnosed within 12 hours of the initial episode (attack) then
thrombolytic therapyThrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...
is initiated.
Other sites
Hepatic artery thrombosis usually occurs as a devastating complication after
liver transplantationLiver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...
.
An arterial embolus can also form in the limbs.
Embolization
If a bacterial infection is present at the site of thrombosis, the thrombus may break down, spreading particles of infected material throughout the
circulatory systemThe circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
(pyemia, septic embolus) and setting up metastatic abscesses wherever they come to rest. Without an infection, the thrombus may become detached and enter circulation as an
embolusIn medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
, finally lodging in and completely obstructing a blood vessel, which unless treated very quickly will lead to tissue necrosis (an
infarctionIn medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
) in the area past the occlusion. If the occlusion is in the coronary artery, myocardial ischaemia is likely to occur, whereby cardiac myocytes cannot function properly due to lack of oxygen. This lack of oxygen is then likely to result in a myocardial infarction.
Most thrombi, however, become
organized into fibrous tissueFibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
, and the thrombosed vessel is gradually recanalized.
Prevention
Thrombosis and embolism can be partially prevented with anticoagulants in those deemed at risk. One of the most common types of venous thrombosis is deep vein thrombosis (DVT), which is a blood clot in one of the deep veins of the body.
Arterial thrombosis often occurs in arteries that supply the heart, resulting in a heart attack. It can also occur in the arteries of the brain, causing a stroke.
Sometimes, part, or all, of a blood clot can come away from its original site and travel through the bloodstream. If this occurs, the clot can become lodged in another part of the body. This is known as an embolism. A blood clot that lodges in one of the lungs is called a pulmonary embolism.
Generally, a risk-benefit analysis is required, as all anticoagulants lead to a small increase in the risk of major bleeding. In
atrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
, for instance, the risk of
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
(calculated on the basis of additional risk factors, such as advanced age and
high blood pressureHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
) needs to outweigh the small but known risk of major bleeding associated with the use of
warfarinWarfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
.
In people admitted to hospital, thrombosis is a major cause for complications and occasionally death. In the UK, for instance, the Parliamentary
Health Select CommitteeThe Health Select Committee is one of the Select Committees of the British House of Commons. It oversees the operations of the Department of Health and its associated bodies.-Membership:...
heard in 2005 that the annual rate of death due to hospital-acquired thrombosis was 25,000. Hence
thromboprophylaxis (prevention of thrombosis) is increasingly emphasized. In patients admitted for surgery, graded
compression stockingsCompression stockings and socks are specialised hosiery items designed to increase blood circulation. Their main theraputic purpose is to provide graduated pressure on the lower leg and foot and, in some cases, the thigh, to alleviate circulatory problems such as edema, phlebitis and...
are widely used, and in severe illness, prolonged immobility and in all
orthopedic surgeryOrthopedic surgery or orthopedics is the branch of surgery concerned with conditions involving the musculoskeletal system...
, professional guidelines recommend
low molecular weight heparinIn medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
(LMWH) administration, mechanical calf compression or (if all else is contraindicated and the patient has recently suffered deep vein thrombosis) the insertion of a
vena cava filterAn inferior vena cava filter, also IVC filter or Greenfield Filter a type of vascular filter, is a medical device that is implanted by interventional radiologists or vascular surgeons into the inferior vena cava to prevent fatal pulmonary emboli .IVC filters are used in case of contraindication to...
. In patients with medical rather than surgical illness, LMWH too is known to prevent thrombosis, and in the
United KingdomThe United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
the Chief Medical Officer has issued guidance to the effect that preventative measures should be used in medical patients, in anticipation of formal guidelines.