|Other names||Blood clot|
|Diagram of a thrombus (blood clot) that has blocked a blood vessel valve|
A thrombus, colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. 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 the 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 entrapped white blood cells and red blood cells (darker).
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, as well as platelets and heparin to prevent further thrombi formation.
Thrombi are classified in three major groups depending on the relative amount of platelets and red blood cells (RBCs). The three major groups are:
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 increase the 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 occurs through injuries that damage the endothelium of the blood vessels, exposing the enzyme called factor VII, a protein normally circulating within the vessels, to the tissue factor, which is a protein encoded by the F3 gene. The platelet activation can potentially cause a cascade, eventually leading to the formation of the thrombus. This process is regulated through thromboregulation.
Blood clot prevention and treatment reduce the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are used to inhibit the formation and growth of existing thrombi, with the former used for acute anticoagulation while the latter is used for long-term anticoagulation. The mechanism of action of heparin and warfarin are different as they work on different pathways of the coagulation cascade. Heparin works by binding to and activating the enzyme inhibitor antithrombin III, an enzyme that acts by inactivating thrombin and factor Xa. In contrast, warfarin works by inhibiting vitamin K epoxide reductase, an enzyme needed to synthesize vitamin K dependent clotting factors II, VII, IX, and X. Bleeding time with heparin and warfarin therapy can be measured with the partial thromboplastin time (PTT) and prothrombin time (PT), respectively.
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 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 , this enzyme has been successfully produced by genetically engineered bacteria and is administered to cardiac patients.
More recent research indicates that tPA could have toxic effects in the central nervous system. In cases of severe stroke, tPA can cross the blood-brain barrier and enter interstitial fluid, where it then increases excitotoxicity, potentially affecting permeability of the blood-brain barrier, and may even cause cerebral hemorrhaging.
Thrombus formation can have one of four outcomes: propagation, embolization, dissolution, and organization and recanalization.