An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which help keep the bite area unclotted long enough for the animal to obtain blood.
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 stop and prevent further bleeding, but can be harmful in thrombosis, when a clot obstructs blood flow through a healthy blood vessel in the circulatory system.
Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and, in the treatment of venous thromboembolism, and the treatment of myocardial infarction.
Coagulation factor VII is a protein involved in coagulation and, in humans, is encoded by gene F7. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa, which in turn activates factor IX and factor X.
Coagulation factor X, or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by F10 gene. It is a serine endopeptidase. Factor X is synthesized in the liver and requires vitamin K for its synthesis.
Hirudin is a naturally occurring peptide in the salivary glands of blood-sucking leeches that has a blood anticoagulant property. This is essential 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.
The prothrombinase enzyme complex consists of factor Xa (a serine protease) and factor Va (a protein cofactor). 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.
Tissue factor pathway inhibitor is a single-chain polypeptide which can reversibly inhibit factor Xa (Xa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the FVIIa-tissue factor complex. TFPI contributes significantly to the inhibition of Xa in vivo, despite being present at concentrations of only 2.5 nM.
Rivaroxaban, sold under the brand name Xarelto among others, is an anticoagulant medication used to treat and prevent blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prevent blood clots in atrial fibrillation and following hip or knee surgery. It is taken by mouth.
Otamixaban (INN) is an experimental injectable anticoagulant direct factor Xa inhibitor that was investigated for the treatment for acute coronary syndrome. In 2013, Sanofi announced that it had ended development of the drug candidate after poor performance in a Phase III clinical trial.
Glossiphoniidae are a family of freshwater proboscis-bearing leeches. These leeches are generally flattened, and have a poorly defined anterior sucker. Most suck the blood of freshwater vertebrates like amphibians, crocodilians and aquatic turtles, but some feed on invertebrates like oligochaetes and freshwater snails instead. Although they prefer other hosts, blood-feeding species will opportunistically feed from humans.
Direct factor Xa inhibitors (xabans) are anticoagulants, used to both treat and prevent blood clots in veins, and prevent stroke and embolism in people with atrial fibrillation (AF).
Haementeria ghilianii, commonly known as the Amazon giant leech, is one of the world's largest species of leeches.
Betrixaban is an oral anticoagulant drug which acts as a direct factor Xa inhibitor. Betrixaban is FDA approved for venous thrombosis prevention in adults hospitalized for an acute illness who are at risk for thromboembolic complications. Compared to other directly acting oral anticoagulants betrixaban has relatively low renal excretion and is not metabolized by CYP3A4.
In molecular biology, haemadin is an anticoagulant peptide synthesised by the Indian leech, Haemadipsa sylvestris. It adopts a secondary structure consisting of five short beta-strands (beta1-beta5), which are arranged in two antiparallel distorted sheets formed by strands beta1-beta4-beta5 and beta2-beta3 facing each other. This beta-sandwich is stabilised by six enclosed cysteines arranged in a [1-2, 3-5, 4-6] disulfide pairing resulting in a disulfide-rich hydrophobic core that is largely inaccessible to bulk solvent. The close proximity of disulfide bonds [3-5] and [4-6] organises haemadin into four distinct loops. The N-terminal segment of this domain binds to the active site of thrombin, inhibiting it.
Darexaban (YM150) is a direct inhibitor of factor Xa created by Astellas Pharma. It is an experimental drug that acts as an anticoagulant and antithrombotic to prevent venous thromboembolism after a major orthopaedic surgery, stroke in patients with atrial fibrillation and possibly ischemic events in acute coronary syndrome. It is used in form of the maleate. The development of darexaban was discontinued in September 2011.
Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. DTIs have undergone rapid development since the 90's. With technological advances in genetic engineering the production of recombinant hirudin was made possible which opened the door to this new group of drugs. Before the use of DTIs the therapy and prophylaxis for anticoagulation had stayed the same for over 50 years with the use of heparin derivatives and warfarin which have some well known disadvantages. DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric and multi-mechanism inhibitors might lead the way to a safer anticoagulant.
Andexanet alfa, sold under the brand name Andexxa among others, is an antidote for the medications rivaroxaban and apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding. It has not been found to be useful for other factor Xa inhibitors. It is given by injection into a vein.
Four drugs from the class of direct Xa inhibitors are marketed worldwide. Rivaroxaban (Xarelto) was the first approved FXa inhibitor to become commercially available in Europe and Canada in 2008. The second one was apixaban (Eliquis), approved in Europe in 2011 and in the United States in 2012. The third one edoxaban was approved in Japan in 2011 and in Europe and the US in 2015. Betrixaban (Bevyxxa) was approved in the US in 2017.
Haementeria is a genus of leeches in the family Glossiphoniidae. The genus was described in 1849 by Filippo De Filippi.
