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).
|Other names||Blood clot|
|Diagram of a thrombus (blood clot) that has blocked a blood vessel valve|
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 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 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.
Abciximab or Abcixifiban (previously known as c7E3 Fab), a glycoprotein IIb/IIIa receptor antagonist manufactured by Janssen Biologics BV and distributed by Eli Lilly under the trade name ReoPro, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures like angioplasty to prevent platelets from sticking together and causing thrombus (blood clot) formation within the coronary artery. It is a glycoprotein IIb/IIIa inhibitor.While abciximab has a short plasma half-life, due to its strong affinity for its receptor on the platelets, it may occupy some receptors for weeks. In practice, platelet aggregation gradually returns to normal about 96 to 120 hours after discontinuation of the drug. Abciximab is made from the Fab fragments of an immunoglobulin that targets the glycoprotein IIb/IIIa receptor on the platelet membrane.Acetylsalicylic acid/dipyridamole
The combination drug acetylsalicylic acid/dipyridamole (trade names Aggrenox, Asasantin) is a drug combination of:
Acetylsalicylic acid, the analgesic otherwise (but in higher doses) trademarked as Aspirin
Dipyridamole, a drug that inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over short time.The combination acts as an extended release formulation and is primarily used for platelet inhibition in patients suffering, or at risk from, acute coronary events and stroke. Its use has been shown to be better than the use of either dipyridamole or aspirin alone.Antithrombotic
An antithrombotic agent is a drug that reduces the formation of blood clots (thrombi). Antithrombotics can be used therapeutically for prevention (primary prevention, secondary prevention) or treatment of a dangerous blood clot (acute thrombus). In the U.S., the American College of Chest Physicians publishes clinical guidelines for clinicians for the use of these drugs to treat and prevent a variety of diseases.Cerebral infarction
A cerebral infarction is an area of necrotic tissue in the brain resulting from a blockage or narrowing in the arteries supplying blood and oxygen to the brain. The restricted oxygen due to the restricted blood supply causes an ischemic stroke that can result in an infarction if the blood flow is not restored within a relatively short period of time. The blockage can be due to a thrombus, an embolus or an atheromatous stenosis of one or more arteries. Which arteries are problematic will determine which areas of the brain are affected (infarcted). These varying infarcts will produce different symptoms and outcomes. About one third will prove fatal.Coagulopathy
Coagulopathy (also called a bleeding disorder) is a condition in which the blood’s ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur spontaneously or following an injury or medical and dental procedures. Of note, coagulopathies are sometimes erroneously referred to as "clotting disorders"; a clotting disorder is a predisposition to clot formation (thrombus), also known as a hypercoagulable state or thrombophilia.Embolism
An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), or foreign material. An embolism can cause partial or total blockage of blood flow in the affected vessel. Such a blockage (a vascular occlusion) may affect a part of the body distant from the origin of the embolus. An embolism in which the embolus is a piece of thrombus is called a thromboembolism.
An embolism is usually a pathological event, i.e., accompanying illness or injury. Sometimes it is created intentionally for a therapeutic reason, such as to stop bleeding or to kill a cancerous tumor by stopping its blood supply. Such therapy is called embolization.Embolus
An embolus (plural emboli; from the Greek ἔμβολος "wedge", "plug") is an unattached mass that travels through the bloodstream and is capable of clogging arterial capillary beds (create an arterial occlusion) at a site distant from its point of origin. There are a number of different types of emboli, including blood clots, cholesterol plaque or crystals, fat globules, gas bubbles, and foreign bodies.
By contrast there are non-traveling blockages that develop locally from vascular trauma or epithelial pathology and vascular inflammation — such as atheromata and thrombi. However, if a thrombus breaks loose from its genesis site it becomes a thrombo-embolus and if not broken down during transit, may cause embolism(s).The term was coined in 1848 by Rudolf Virchow.Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis. The primary type is a normal body process, whereas secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause.In fibrinolysis, a fibrin clot, the product of coagulation, is broken down. Its main enzyme plasmin cuts the fibrin mesh at various places, leading to the production of circulating fragments that are cleared by other proteases or by the kidney and liver.Left ventricular thrombus
Left ventricular thrombus is a blood clot (thrombus) in the left ventricle of the heart. LVT is a common complication of acute myocardial infarction (AMI). Typically the clot is a mural thrombus, meaning it is on the wall of the ventricle. The primary risk of LVT is the occurrence of cardiac embolism, in which the thrombus detaches from the ventricular wall and travels through the circulation and blocks blood vessels. Blockage can be especially damaging in the heart or brain (stroke).Lines of Zahn
Lines of Zahn are a characteristic of thrombi that appear particularly when formed in the heart or aorta. They have visible and microscopic alternating layers (laminations) of platelets mixed with fibrin, which appear lighter and darker layers of red blood cells. Their presence implies thrombosis at a site of rapid blood flow that happened before death. In veins or smaller arteries, where flow is not as constant, they are less apparent.
They are named after German–Swiss pathologist Friedrich Wilhelm Zahn.Paradoxical embolism
A paradoxical embolism refers to an embolus which is carried from the venous side of circulation to the arterial side, or vice versa. It is a kind of stroke or other form of arterial thrombosis caused by embolism of a thrombus (blood clot), air, tumor, fat, or amniotic fluid of venous origin, which travels to the arterial side through a lateral opening in the heart, such as a patent foramen ovale, or arteriovenous shunts in the lungs.
The opening is typically an atrial septal defect, but can also be a ventricular septal defect.
Paradoxical embolisms represent two percent of arterial emboli.Phosphorylcholine
Phosphorylcholine refers to the functional group derived from phosphocholine. Also not to be confused with phosphatidylcholine.Phosphorylcholine (abbreviated ChoP) is the hydrophilic polar head group of some phospholipids, which is composed of a negatively charged phosphate bonded to a small, positively charged choline group. Phosphorylcholine is part of platelet-activating factor; the phospholipid phosphatidylcholine as well as sphingomyelin, the only phospholipid of the membrane that is not built with a glycerol backbone. Treatment of cell membranes, like those of RBCs, by certain enzymes, like some phospholipase A2 renders the phosphorylcholine moiety exposed to the external aqueous phase, and thus accessible for recognition by the immune system. Antibodies against phosphorylcholine are naturally occurring autoantibodies that are created by CD5+/B-1 B cells and are referred to as non-pathogenic autoantibodies.Taotao (giant panda)
Taotao (Chinese: 涛涛 c. 1972 – April 2, 2008) was a Chinese giant panda. Taotao was China's oldest living giant panda at the time of her death at the age of 36.Taotao was born in the wild in Gansu province, and in October 1994 was brought to the zoo in Jinan in the Shandong province. Taotao never gave birth in captivity, despite the efforts of researchers and zoo keepers.Taotao was considered to be one of the Jinan Zoo's star attractions and was seen by millions of visitors from 1994 to 2008. The Jinan Zoo reportedly bestowed the title of "ambassador of harmonious zoology" on Taotao.Taotao died from brain thrombus and a cerebral hemorrhage on April 2, 2008, at the Jinan Zoo. She had been in declining health since the brain thrombus disease was discovered in February 2008. Taotao lived far beyond the average life expectancy of a giant panda, who usually live to the age of 25 years. Taotao's remains will reportedly be returned to Gansu province.As of 2008, over 200 of the giant pandas that are native to China live in captivity around the world.Tenecteplase
Tenecteplase (sold under the trade name TNKase) is an enzyme used as a thrombolytic drug.
Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain.
Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.
The abbreviation TNK is common for referring to tenecteplase, but abbreviating drug names is not best practice in medicine, and in fact "TNK" is one of the examples given on the Institute for Safe Medication Practices (ISMP) do-not-use list.Thrombogenicity
Thrombogenicity refers to the tendency of a material in contact with the blood to produce a thrombus, or clot. It not only refers to fixed thrombi but also to emboli, thrombi which have become detached and travel through the bloodstream. Thrombogenicity can also encompass events such as the activation of immune pathways and the complement system. All materials are considered to be thrombogenic with the exception of the normal state of endothelial cells which line blood vessels. Certain medical implants appear non-thrombogenic due to high flow rates of blood past the implant, but in reality all are thrombogenic to a degree. Various surface treatments are available to minimize these thrombogenic effects.
A thrombogenic implant will eventually be covered by a fibrous capsule, the thickness of this capsule can be considered one measure of thrombogenicity, and if extreme can lead to the failure of the implant.Thrombophlebitis
Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot).When it occurs repeatedly in different locations, it is known as thrombophlebitis migrans, (migrating thrombophlebitis)Thrombosis
Thrombosis (from Ancient Greek θρόμβωσις thrómbōsis "clotting”) is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.Thrombosis may occur in veins (venous thrombosis) or in arteries (arterial thrombosis). Venous thrombosis leads to congestion of the affected part of the body, while arterial thrombosis (and rarely severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery (ischemia and necrosis). A piece of either an arterial or a venous thrombus can break off as an embolus which can travel through the circulation and lodge somewhere else as an embolism. This type of embolism is known as a thromboembolism. Complications can arise when a venous thromboembolism (commonly called a VTE) lodges in the lung as a pulmonary embolism. An arterial embolus may travel further down the affected blood vessel where it can lodge as an embolism.Thrombus perviousness
Thrombus perviousness is an imaging biomarker which is used to estimate clot permeability from CT imaging. It reflects the ability of artery-occluding thrombi to let fluid seep into and through them. The more pervious a thrombus, the more fluid it lets through. Thrombus perviousness can be measured using radiological imaging routinely performed in the clinical management of acute ischemic stroke: CT scans without intravenous contrast (also called non-contrast CT, in short NCCT) combined with CT scans after intravenously administered contrast fluid (CT-angiography, in short CTA). Pervious thrombi may let more blood pass through to the ischemic brain tissue, and/or have a larger contact surface and histopathology more sensitive for thrombolytic medication. Thus, patients with pervious thrombi may have less brain tissue damage by stroke. The value of thrombus perviousness in acute ischemic stroke treatment is currently being researched.Venous thrombosis
A venous thrombus is a blood clot (thrombus) that forms within a vein. Thrombosis is a term for a blood clot occurring inside a blood vessel. A common type of venous thrombosis is a deep vein thrombosis (DVT), which is a blood clot in the deep veins of the leg. If the thrombus breaks off (embolizes) and flows towards the lungs, it can become a pulmonary embolism (PE), a blood clot in the lungs.
An inflammatory reaction is usually present, mainly in the superficial veins and, for this reason this pathology is called most of the time thrombophlebitis. The inflammatory reaction and the white blood cells play a role in the resolution of venous clots.The initial treatment for venous thromboembolism is typically with either low molecular weight heparin (LMWH) or unfractionated heparin. LMWH appears to have lower rates of side effects; however, both result in similar rates of survival.
Disorders of blood flow