Thrombosis

Thrombosis (Greek: θρόμβωσις) is the formation of a blood clot (thrombus; Greek: θρόμβος) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin 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 embolus.

Thromboembolism is the combination of thrombosis and its main complication, embolism.

When a thrombus occupies more than 75% of surface area of the lumen of an artery, blood flow to the tissue supplied is reduced enough to cause symptoms because of decreased oxygen (hypoxia) and accumulation of metabolic products like lactic acid. More than 90% obstruction can result in anoxia, the complete deprivation of oxygen, and infarction, a mode of cell death.

Causes
In classical terms, thrombosis is caused by abnormalities in one or more of the following (Virchow's triad):
 * 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 factor 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 stasis which may occur in heart failure or after long periods of sedentary behavior— for example, sitting on a long airplane flight. Also, atrial fibrillation, 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 vein. 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 vein. It most commonly affects leg veins, such as the femoral 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 swelling, pain and redness of the affected area.

Portal vein thrombosis
Portal vein thrombosis is a form of venous thrombosis affecting the hepatic portal vein, which can lead to portal hypertension and reduction of the blood supply to the liver. It usually has a pathological cause such as pancreatitis, cirrhosis, diverticulitis or cholangiocarcinoma.

Renal vein thrombosis
Renal vein thrombosis is the obstruction of the renal vein 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 sepsis, pulmonary embolism, and papilledema. 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 vein or the inferior vena cava. This form of thrombosis presents with abdominal pain, ascites and hepatomegaly. Treatment varies between therapy and surgical intervention by the use of shunts.

Paget-Schroetter disease
Paget-Schroetter disease is the obstruction of an upper extremity vein (such as the axillary vein or subclavian vein) 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 stroke which results from the blockage of the dural venous sinuses by a thrombus. Symptoms may include headache, 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 CT or MRI scan. The majority of persons affected make a full recovery. The mortality rate is 4.3%.

Arterial thrombosis
Arterial thrombosis is the formation of a thrombus within an artery. In most cases, arterial thrombosis follows rupture of atheroma, and is therefore referred to as atherothrombosis.

Another common cause of arterial thrombosis is atrial fibrillation, which causes disturbed blood flow. In addition, it is well known that the direct current cardioversion 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 embolism, potentially causing infarction 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 ischemia, thrombus, embolus (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, vertebral and the circle of Willis. 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 therapy is initiated.

Other sites
Hepatic artery thrombosis usually occurs as a devastating complication after liver transplantation.

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 system (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 embolus, finally lodging in and completely obstructing a blood vessel, which unless treated very quickly will lead to tissue necrosis (an infarction) 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 tissue, 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 fibrillation, for instance, the risk of stroke (calculated on the basis of additional risk factors, such as advanced age and high blood pressure) needs to outweigh the small but known risk of major bleeding associated with the use of warfarin.

In people admitted to hospital, thrombosis is a major cause for complications and occasionally death. In the UK, for instance, the Parliamentary Health Select Committee 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 stockings are widely used, and in severe illness, prolonged immobility and in all orthopedic surgery, professional guidelines recommend low molecular weight heparin (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 filter. In patients with medical rather than surgical illness, LMWH too is known to prevent thrombosis, and in the United Kingdom the Chief Medical Officer has issued guidance to the effect that preventative measures should be used in medical patients, in anticipation of formal guidelines.