Thrombin–antithrombin complex

Last updated

Thrombin–antithrombin complex (TAT) is a protein complex of thrombin and antithrombin. [1] [2]

Contents

TAT formation

TAT is formed in response to the high thrombin level caused by coagulation following a ruptured vessel. Since thrombin is rapidly bound by antithrombin, TAT is a good measure for thrombin level in the blood. Thrombin can pass the blood-brain barrier, destroying neurons and potentially causing cerebral edemas. [3]

TAT and intracerebral hemorrhage (ICH)

TAT levels were studied in patients with intracranial blood clot removal within 24 hours after intracerebral hemorrhage (ICH) in Fujian from 2006–2008. This study revealed that TAT levels in the plasma and hematoma fluid of these patients are higher than that those of healthy people, and that TAT levels decreased in the patients after surgery and increased in the patients that had a hemorrhage again. The TAT levels correlate with the severity of ICH according to GCS and NIHSS, and so, the study concluded that TAT complex may be useful in the prognosis for post-operative ICH-patients. [3]

Related Research Articles

Bleeding Loss of blood escaping from the circulatory system

Bleeding, also known as a hemorrhage, haemorrhage, or simply blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vagina or anus, or through a wound in the skin. Hypovolemia is a massive decrease in blood volume, and death by excessive loss of blood is referred to as exsanguination. Typically, a healthy person can endure a loss of 10–15% of the total blood volume without serious medical difficulties. The stopping or controlling of bleeding is called hemostasis and is an important part of both first aid and surgery. The use of cyanoacrylate glue to prevent bleeding and seal battle wounds was designed and first used in the Vietnam War. Today many medical treatments use a medical version of "super glue" instead of using traditional stitches used for small wounds that need to be closed at the skin level.

Thrombus blood clot

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.

Coagulation Process by which blood changes from a liquid to a gel, forming a blood clot

Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.

Disseminated intravascular coagulation pathological process characterized by the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body

Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts of the body. As clotting factors and platelets are used up, bleeding may occur. This may include blood in the urine, blood in the stool, or bleeding into the skin. Complications may include organ failure.

Fibrinogen Soluble protein complex in blood plasma and involved in clot formation

Fibrinogen is a glycoprotein complex that circulates in the blood of vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clot. Fibrin clots function primarily to occlude blood vessels to stop bleeding. Fibrin also binds and reduces the activity of thrombin. This activity, sometimes referred to as antithrombin I, limits clotting. Fibrin also mediates blood platelet and endothelial cell spreading, tissue fibroblast proliferation, capillary tube formation, and angiogenesis and thereby promotes revascularization and wound healing.

Thrombin Enzyme in humans

Thrombin is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.

Antithrombin mammalian protein found in Homo sapiens

Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites. α-Antithrombin is the dominant form of antithrombin found in blood plasma and has an oligosaccharide occupying each of its four glycosylation sites. A single glycosylation site remains consistently un-occupied in the minor form of antithrombin, β-antithrombin. Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to factor IIa (Thrombin) and factor Xa.

Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and treatment of venous thromboembolism and in the treatment of myocardial infarction.

Subdural hematoma Hematoma usually associated with traumatic brain injury

A subdural hematoma (SDH) is a type of bleeding in which a collection of blood—usually associated with a traumatic brain injury—gathers between the inner layer of the dura mater and the arachnoid mater of the meninges surrounding the brain. It usually results from tears in bridging veins that cross the subdural space.

Intracranial hemorrhage hemorrhage, or bleeding, within the skull

Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds, subarachnoid bleeds, epidural bleeds, and subdural bleeds.

Factor VII mammalian protein found in Homo sapiens

Factor VII is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class. A recombinant form of human factor VIIa has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market.

Hirudin chemical compound

Hirudin is a naturally occurring peptide in the salivary glands of blood-sucking leeches that has a blood anticoagulant property. This is fundamental for the leeches’ alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy performed by the worm on the host’s skin.

Fresh frozen plasma

Fresh frozen plasma (FFP) is a blood product made from the liquid portion of whole blood. It is used to treat conditions in which there are low blood clotting factors (INR>1.5) or low levels of other blood proteins. It may also be used as the replacement fluid in plasma exchange. Using ABO compatible plasma, while not required, may be recommended. Use as a volume expander is not recommended. It is given by slow injection into a vein.

Intracerebral hemorrhage Type of intracranial bleeding that occurs within the brain tissue itself

Intracerebral hemorrhage (ICH), also known as cerebral bleed, is a type of intracranial bleed that occurs within the brain tissue or ventricles. Symptoms can include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness. Often symptoms get worse over time. Fever is also common. In many cases bleeding is present in both the brain tissue and the ventricles.

The prothrombinase complex consists of the serine protease, Factor Xa, and the protein cofactor, Factor Va. The complex assembles on negatively charged phospholipid membranes in the presence of calcium ions. The prothrombinase complex catalyzes the conversion of prothrombin (Factor II), an inactive zymogen, to thrombin (Factor IIa), an active serine protease. The activation of thrombin is a critical reaction in the coagulation cascade, which functions to regulate hemostasis in the body. To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg271 and the other after Arg320. Although it has been shown that Factor Xa can activate prothrombin when unassociated with the prothrombinase complex, the rate of thrombin formation is severely decreased under such circumstances. The prothrombinase complex can catalyze the activation of prothrombin at a rate 3 x 105-fold faster than can Factor Xa alone. Thus, the prothrombinase complex is required for the efficient production of activated thrombin and also for adequate hemostasis.

Hypoprothrombinemia Human disease

Hypoprothrombinemia is a rare blood disorder in which a deficiency in immunoreactive prothrombin, produced in the liver, results in an impaired blood clotting reaction, leading to an increased physiological risk for spontaneous bleeding. This condition can be observed in the gastrointestinal system, cranial vault, and superficial integumentary system, effecting both the male and female population. Prothrombin is a critical protein that is involved in the process of hemostasis, as well as illustrating procoagulant activities. This condition is characterized as an autosomal recessive inheritance congenital coagulation disorder affecting 1 per 2,000,000 of the population, worldwide, but is also attributed as acquired.

Heparin cofactor II protein-coding gene in the species Homo sapiens

Heparin cofactor II (HCII), a protein encoded by the SERPIND1 gene, is a coagulation factor that inhibits IIa, and is a cofactor for heparin and dermatan sulfate.

Osmotherapy

Osmotherapy is the use of osmotically active substances to reduce the volume of intracranial contents. Osmotherapy serves as the primary medical treatment for cerebral edema. The primary purpose of osmotherapy is to improve elasticity and decrease intracranial volume by removing free water, accumulated as a result of cerebral edema, from brain's extracellular and intracellular space into vascular compartment by creating an osmotic gradient between the blood and brain. Normal serum osmolality ranges from 280-290 mOsm/kg and serum osmolality to cause water removal from brain without much side effects ranges from 300-320 mOsm/kg. Usually, 90 mL of space is created in the intracranial vault by 1.6% reduction in brain water content. Osmotherapy has cerebral dehydrating effects. The main goal of osmotherapy is to decrease intracranial pressure(ICP) by shifting excess fluid from brain. This is accomplished by intravenous administration of osmotic agents which increase serum osmolality in order to shift excess fluid from intracellular or extracellular space of the brain to intravascular compartment. The resulting brain shrinkage effectively reduces intracranial volume and decreases ICP.

Antithrombin III deficiency is a deficiency of antithrombin III. This deficiency may be inherited or acquired. It is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism, and repetitive intrauterine fetal death (IUFD). Hereditary antithrombin deficiency results in a state of increased coagulation which may lead to venous thrombosis. Inheritance is usually autosomal dominant, though a few recessive cases have been noted. The disorder was first described by Egeberg in 1965. The causes of acquired antithrombin deficiency are easier to find than the hereditary deficiency.

Batroxobin, also known as reptilase, is a snake venom enzyme with Venombin A activity produced by Bothrops atrox and Bothrops moojeni, venomous species of pit viper found east of the Andes in South America. It is a hemotoxin which acts as a serine protease similarly to thrombin, and has been the subject of many medical studies as a replacement of thrombin. Different enzymes, isolated from different species of Bothrops, have been called batroxobin, but unless stated otherwise, this article covers the batroxobin produced by B. moojeni, as this is the most studied variety.

References

  1. Lippi G, Cervellin G, Franchini M, Favaloro EJ (2010). "Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future". J. Thromb. Thrombolysis. 30 (4): 459–71. doi:10.1007/s11239-010-0460-x. PMID   20213258.
  2. Zwicker JI, Furie BC, Furie B (2007). "Cancer-associated thrombosis". Crit. Rev. Oncol. Hematol. 62 (2): 126–36. doi:10.1016/j.critrevonc.2007.01.001. PMID   17293122.
  3. 1 2 Wu, C. -H.; Yang, R. -L.; Huang, S. -Y.; Li, H. -Z.; Wang, K. -Y.; Yang, D. -H.; Yan, X. -H.; Xue, X. -H.; Wu, S. -Y. (August 2011). "Analysis of thrombin-antithrombin complex contents in plasma and hematoma fluid of hypertensive intracerebral hemorrhage patients after clot removal: TAT in ICH patients". European Journal of Neurology. 18 (8): 1060–1066. doi:10.1111/j.1468-1331.2010.03336.x. PMID   21244583.