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A thrombus, or colloquially a blood clot, is the final product of the blood coagulation step in hemostasis. Note, a thrombus is a solid or semi-solid mass formed from the constituents of blood within the vascular system during life, whereas a blood clot refers to one that is formed post-mortem. There are two components to a thrombus, aggregated platelets that form a platelet plug, and a mesh of cross-linked fibrin protein. A thrombus is a healthy response to injury intended to prevent bleeding, but can be harmful in thrombosis, when clots obstruct blood flow through healthy blood vessels.
Mural thrombi are thrombi that adhere to the wall of a blood vessel. They occur in large vessels such as heart and aorta, and can restrict blood flow but usually do not block it entirely. They appear grey-red with alternating light and dark lines (known as lines of Zahn) which represent bands of fibrin (lighter) with entrapped white blood cells and red blood cells (darker).
A thrombus occurs when the hemostatic process, which normally occurs in response to injury, becomes activated in an uninjured or slightly injured vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel (termed a mural thrombus). In a small blood vessel, blood flow may be completely cut off (termed an occlusive thrombus), resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is considered an embolus.
Some of the conditions which elevate risk of blood clots developing include atrial fibrillation (a form of cardiac arrhythmia), heart valve replacement, a recent heart attack (also known as a myocardial infarction), extended periods of inactivity (see deep venous thrombosis), and genetic or disease-related deficiencies in the blood's clotting abilities.
Platelet activation can occur through different mechanisms such as a vessel wall breach that exposes collagen, or tissue factor encryption. The platelet activation causes a cascade of further platelet activation eventually causing the formation of the thrombus. This process is regulated through thromboregulation.
Blood clot prevention and treatment reduces the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are often used to inhibit the formation and growth of existing thrombi; the former binds to and activates the enzyme inhibitor antithrombin III, while the latter inhibits vitamin K epoxide reductase, an enzyme needed to synthesize mature clotting factors.
Some treatments have been derived from bacteria. One drug is streptokinase, which is an enzyme secreted by several streptococcal bacteria. This drug is administered intravenously and can be used to dissolve blood clots in coronary vessels. However, streptokinase is nonspecific and can digest almost any protein, which can lead to many secondary problems. Another clot-dissolving enzyme that works faster and is more specific is called tissue plasminogen activator (tPA). This drug is made by transgenic bacteria and it converts plasminogen into the clot-dissolving enzyme plasmin. There are also some anticoagulants that come from animals that work by dissolving fibrin. For example, Haementeria ghilianii, an Amazon leech, produces an enzyme called hementin from its salivary glands. As of 2012[update], this enzyme has now been successfully produced by genetically engineered bacteria and administered to cardiac patients.
A recent multicenter randomized trial (DUET) compared standard catheter-directed thrombolysis (CDT) versus ultrasound-accelerated thrombolysis (USAT, EKOS Corporation) for the treatment of acute peripheral arterial thrombotic occlusions. Results showed that, on average, patients treated with USAT were completed 12 hours sooner than those treated with standard CDT with no increase in "serious adverse events." Plans are underway to commence the DUET II study, which will be a non-randomized trial using the EKOS system with an even lower hourly drug dose with an expectation of further reducing bleeding complications.
Recent research shows that chemicals found in certain foods as onions, apples and oranges could help prevent blood clots. Researchers claim that rutin found in black and green teas also could help prevent the formation of clots and therefore could help in future treatments to protect against strokes and heart attacks.
Virchow's triad describes the pathogenesis of thrombus formation:
Disseminated intravascular coagulation (DIC) involves widespread microthrombi formation throughout the majority of the blood vessels. This is due to excessive consumption of coagulation factors and subsequent activation of fibrinolysis using all of the body's available platelets and clotting factors. The end result is hemorrhaging and ischaemic necrosis of tissue/organs. Causes are septicaemia, acute leukaemia, shock, snake bites, fat emboli from broken bones, or other severe traumas. DIC may also be seen in pregnant females. Treatment involves the use of fresh frozen plasma to restore the level of clotting factors in the blood, platelets and heparin to prevent further thrombi formation.
Thoracic aortic thrombus is a rare pathology that usually originates from an atherosclerotic aortic wall lesion or an aortic aneurysm and is a potential source of visceral, cerebral and peripheral embolism.
Thrombus formation can have one of four outcomes: propagation, embolization, dissolution, and organization and recanalization.
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