Reptilase Time
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Reptilase Time
Reptilase time (RT) is a blood test used to detect deficiency or abnormalities in fibrinogen, especially in cases of heparin contamination. Reptilase, an enzyme found in the venom of Bothrops snakes, has activity similar to thrombin. Unlike thrombin, reptilase is resistant to inhibition by antithrombin III. Thus, the reptilase time is not prolonged in blood samples containing heparin, hirudin, or direct thrombin inhibitors, whereas the thrombin time will be prolonged in these samples. Reptilase also differs from thrombin by releasing fibrinopeptide A, but not fibrinopeptide B, in its cleavage of fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl .... References Blood tests {{pathology-stub ...
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Blood Test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholesterol test, are often grouped together into one test panel called a blood panel or blood work. Blood tests are often used in health care to determine physiological and biochemical states, such as disease, mineral content, pharmaceutical drug effectiveness, and organ function. Typical clinical blood panels include a basic metabolic panel or a complete blood count. Blood tests are also used in drug tests to detect drug abuse. Extraction A venipuncture is useful as it is a minimally invasive way to obtain cells and extracellular fluid ( plasma) from the body for analysis. Blood flows throughout the body, acting as a medium that provides oxygen and nutrients to tissues and carries waste products back to the excretory systems for disposal. Co ...
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Fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all 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. Reduced and/or dysfunctional fibrinogens occur in various congenital and acquired human fibrinogen-related disorders. These disorders represent a group of rare conditions in which individuals may present with severe episodes of pathological bleeding and thrombosis; these conditions are treated by supplementing blood fibrinogen levels an ...
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Heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given intravenously or by injection under the skin. Other uses for its anticoagulant properties include inside blood specimen test tubes and kidney dialysis machines. Common side effects include bleeding, pain at the injection site, and low blood platelets. Serious side effects include heparin-induced thrombocytopenia. Greater care is needed in those with poor kidney function. Heparin is contraindicated for suspected cases of vaccine-induced pro-thrombotic immune thrombocytopenia (VIPIT) secondary to SARS-CoV-2 vaccination, as heparin may further increase the risk of bleeding in an anti-PF4/heparin complex autoimmune manner, in favor of alternative anticoagulant medications (such as arg ...
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Reptilase
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. History Bothrops atrox was described by Carl Linnaeus as early as 1758, but batroxobin, the active compound in its venom, was first described only in 1954 by H. Bruck and G. Salem. In the years following, this first description of batroxobin was shown to have several uses in surgery. Because of the increasing interest in the properties of batroxobin, several studies on its hemostatic effect and ...
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Venom
Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a stinger, in a process called envenomation. Venom is often distinguished from poison, which is a toxin that is passively delivered by being ingested, inhaled, or absorbed through the skin, and toxungen, which is actively transferred to the external surface of another animal via a physical delivery mechanism. Venom has evolved in terrestrial and marine environments and in a wide variety of animals: both predators and prey, and both vertebrates and invertebrates. Venoms kill through the action of at least four major classes of toxin, namely necrotoxins and cytotoxins, which kill cells; neurotoxins, which affect nervous systems; myotoxins, which damage muscles; and haemotoxins, which disrupt blood clotting. Venomous animals cause tens of thousa ...
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Bothrops
''Bothrops'' is a genus of highly venomous pit vipers endemic to Central and South America.McDiarmid RW, Campbell JA, Touré T. 1999. ''Snake Species of the World: A Taxonomic and Geographic Reference, vol. 1''. Herpetologists' League. 511 pp. (series). (volume). The generic name, ''Bothrops'', is derived from the Greek words βόθρος, ''bothros'', meaning "pit", and ώπς, ''ops'', meaning "eye" or "face", together an allusion to the heat-sensitive loreal pit organs. Members of this genus are responsible for more human deaths in the Americas than any other group of venomous snakes.Campbell JA, Lamar WW. 2004. ''The Venomous Reptiles of the Western Hemisphere''. Comstock Publishing Associates, Ithaca and London. 870 pp. 1500 plates. . Currently, 48 species are recognized. Description These snakes range from small, never growing to more than , to large at over in total length. Most are characterized by having a sharp ''canthus rostralis'' and an unelevated snout. The arra ...
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Thrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma-thrombin'') is a serine protease, an enzyme that, in humans, is encoded by the ''F2'' gene. Prothrombin (coagulation factor II) 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. History After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872. Prothrombin was discovered by Pekelharing in 1894. Physiology Synthesis Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly ...
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Antithrombin III
Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 432-amino-acid protein produced by the liver. 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 thrombin, factor IIa (prothrombin) and factor Xa. Nomenclature Antithrombin is also termed antithrombin III (AT III). The designations antithrombin I through to antithrombin IV originate in early studies carried out in the 1950s by Seegers, Johnson and Fell. Antithrombin I (AT I) refers to the absorption of thrombin onto fibrin after thrombin has activated fibrinogen. He ...
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Hirudin
Hirudin is a naturally occurring peptide in the salivary glands of blood-sucking leeches (such as ''Hirudo medicinalis'') that has a blood anticoagulant property. This is fundamental for the leeches’ habit of feeding on blood, since it keeps a host's blood flowing after the worm's initial puncture of the skin. Hirudin (MEROPS I14.001) belongs to a superfamily (MEROPS IM) of protease inhibitors that also includes haemadin (MEROPS I14.002) and antistasin (MEROPS I15). Structure During his years in Birmingham and Edinburgh, John Berry Haycraft had been actively engaged in research and published papers on the coagulation of blood, and in 1884, he discovered that the leech secreted a powerful anticoagulant, which he named hirudin, although it was not isolated until the 1950s, nor its structure fully determined until 1976. Full length hirudin is made up of 65 amino acids. These amino acids are organized into a compact N-terminal domain containing three disulfide bonds and a C-termi ...
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Direct Thrombin Inhibitor
Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting) by directly inhibiting the enzyme thrombin (factor IIa). Some are in clinical use, while others are undergoing clinical development. Several members of the class are expected to replace heparin (and derivatives) and warfarin in various clinical scenarios. Types There are three types of DTIs, dependent on their interaction with the thrombin molecule. ''Bivalent'' DTIs (hirudin and analogs) bind both to the active site and exosite 1, while univalent DTIs bind only to the active site. The third class of inhibitors, which are gaining importance recently, is the allosteric inhibitors. Bivalent Hirudin and derivatives were originally discovered in ''Hirudo medicinalis'': * Hirudin * Bivalirudin (transient inhibition - is cleaved by thrombin) * Lepirudin * Desirudin Univalent Univalent DTIs include: * Argatroban * Inogatran * Melagatran (and its prodrug ximelagatran) * Dabiga ...
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Thrombin Time
The thrombin time (TT), also known as the thrombin clotting time (TCT), is a blood test that measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added. It is used to diagnose blood coagulation disorders and to assess the effectiveness of fibrinolytic therapy. This test is repeated with pooled plasma from normal patients. The difference in time between the test and the 'normal' indicates an abnormality in the conversion of fibrinogen (a soluble protein) to fibrin, an insoluble protein. The thrombin time compares the rate of clot formation to that of a sample of normal pooled plasma. Thrombin is added to the samples of plasma. If the time it takes for the plasma to clot is prolonged, a quantitative (fibrinogen deficiency) or qualitative (dysfunctional fibrinogen) defect is present. In blood samples containing heparin, a substance derived from snake venom called batroxobin (formerly reptilase) is ...
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Fibrinopeptide A
The fibrinopeptides, fibrinopeptide A (FpA) and fibrinopeptide B (FpB), are peptides which are located in the central region of the fibrous glycoprotein fibrinogen (factor I) and are cleaved by the enzyme thrombin (factor IIa) to convert fibrinogen into covalently-linked fibrin (factor IA) monomers. The N-terminal FpA is cleaved from the Aα chains of fibrinogen and FpB from the Bβ chains of fibrinogen, with FpA released before FpB. Subsequent to their formation, fibrin monomers are converted to cross-linked fibrin polymers by the action of thrombin-activated factor XIII (fibrin stabilizing factor), and these fibrin polymers form the backbone of a thrombus (blood clot). Hence, the fibrinopeptides are sensitive markers of fibrinogenesis (fibrin generation), thrombin activity, and coagulation. FpA is a 16-amino acid peptide. The half-life of FpA is very short at approximately 3 to 5 minutes. Hence, FpA levels provide a relatively transient measure of coagulation activ ...
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