Thrombin Health Dictionary

An inactive substance in the blood PLASMA that is the precursor of the ENZYME, thrombin, which clots the blood. The conversion occurs when a blood vessel is damaged and the process of blood COAGULATION occurs.... prothrombin

Also known as thrombokinase, this is an ENZYME formed in the preliminary stages of the COAGULATION of blood. It converts the inactive PROTHROMBIN into the enzyme THROMBIN.... thromboplastin

Heparin is one of the naturally produced ANTICOAGULANTS with a rapid e?ect, which is thought to act by neutralising thrombin (see COAGULATION). Inactive when taken orally, it is normally given intravenously – it may be given for a few days, combined with an oral anticoagulant such as warfarin, to initiate anticoagulation. Low-dose heparin may be given by subcutaneous injection for longer periods, for the prophylaxis of DEEP VEIN THROMBOSIS (DVT) or PULMONARY EMBOLISM in ‘high-risk’ patients, such as those with obesity or a history of thrombosis, or post-operatively. If haemorrhage occurs, withdrawal of heparin is usually su?cient, but protamine sulphate is a rapidly active and speci?c antidote. Prolonged treatment with heparin may cause osteoporosis (see under BONE, DISORDERS OF).... heparin

Anticoagulants are drugs which inhibit COAGULATION of the blood. They are used to prevent and treat abnormal clotting of the blood, to treat THROMBOSIS, and sometimes to prevent or treat STROKE or TRANSIENT ISCHAEMIC ATTACKS OR EPISODES (TIA, TIE). Anticoagulant drugs are also prescribed preventively in major surgery to stop abnormal clotting from occurring; HAEMODIALYSIS is another procedure during which these drugs are used. Anticoagulants are also prescribed to prevent thrombi (clots) forming on prosthetic heart valves after heart surgery.

The drugs are much more e?ective in the treatment and prevention of venous clotting – for example, deep vein thrombosis (DVT), see under VEINS, DISEASES OF – than in preventing thrombosis formation in arteries with their fast-?owing blood in which thrombi contain little ?brin (against which the anticoagulants work) and many PLATELETS.

The main anticoagulants now in use are the natural agent HEPARIN (a quick-acting variety and a low-molecular-weight long-acting type); synthetic oral anticoagulants such as WARFARIN and the less-often-used acenocoumarol and PHENINDIONE; and antiplatelet compounds such as ASPIRIN, clopidogrel dipyridamole and ticlopidines. Fondaparinux is an extract of heparin which can be given once daily by injection; ximelagatran, an inhibitor of thrombin, is being trialled as the ?rst new oral anticoagulant since heparin.

Patients taking anticoagulants need careful medical monitoring and they should carry an Anticoagulant Card with instructions about the use of whatever drug they may be receiving – essential information should the individual require treatment for other medical conditions as well as for thrombosis.... anticoagulants

An inherited disorder in which there is a defect of blood-clotting caused by a de?ciency in the formation of thrombin (see COAGULATION).... athrombia

Coagulation of the blood is the process whereby bleeding (or haemorrhage) is normally arrested in the body. Blood starts to clot as soon as the skin (or other tissue) has been cut. Coagulation is part of the process of HAEMOSTASIS which is the arrest of bleeding from an injured or diseased blood vessel. Haemostasis depends on the combined activities of vascular, platelet (see PLATELETS) and PLASMA elements which are o?set by processes to restrict the accumulation of platelets and FIBRIN to the damaged area.

The three-stage process of coagulation is complex, involving many di?erent substances. There are two cascading pathways of biochemical reactions for activating coagulation of blood. The extrinsic pathway is the main physiological mechanism, which is triggered when blood vessels are damaged, usually by trauma or surgery. The intrinsic pathway is activated by internal disruption of the wall of a blood vessel. The basic pattern is broadly the same for both and is summarised simply as follows:

prothrombin + calcium + thromboplastin

thrombin + ?brinogen

?brin

Prothrombin and calcium are normally present in the blood. Thromboplastin is an enzyme which is normally found in the blood platelets and in tissue cells. When bleeding occurs from a blood vessel, there is always some damage to tissue cells and to the blood platelets. As a result of this damage, thromboplastin is released and comes into contact with the prothrombin and calcium in the blood. In the presence of thromboplastin and calcium, prothrombin is converted into thrombin, which in turn interacts with ?brinogen – a protein always present in the blood – to form ?brin. Fibrin consists of needle-shaped crystals which, with the assistance of the blood platelets, form a ?ne network in which the blood corpuscles become enmeshed. This meshwork, or CLOT as it is known, gradually retracts until it forms a tight mass which, unless the tissue injury is very severe or a major artery has been damaged, prevents any further bleeding. It will thus be seen that clotting, or coagulation, does not occur in the healthy blood vessel because there is no thromboplastin present. There is now evidence suggesting that there is an anti-thrombin substance present in the blood in small amounts, and that this substance antagonises any small amounts of thrombin that may be formed as a result of small amounts of thromboplastin being released.

The clotting or coagulation time is the time taken for blood to clot and can be measured under controlled conditions to ensure that it is normal (3–8 minutes). In certain diseases – HAEMOPHILIA, for example – clotting time is greatly extended and the danger of serious haemorrhage enhanced.... coagulation

n. see trophoblast.

d

dabigatran etexilate a drug used for the prevention of venous thromboembolism following hip or knee replacement surgery and for the prevention of stroke and embolism in patients with atrial fibrillation: it directly inhibits the action of *thrombin. The most common side-effect is haemorrhage.... cytotrophoblast

n. the final product of the process of *blood coagulation, produced by the action of the enzyme thrombin on a soluble precursor fibrinogen. The product thus formed (fibrin monomer) links up (polymerizes) with similar molecules to give a fibrous meshwork that forms the basis of a blood clot, which seals off the damaged blood vessel.... fibrin

n. a substance (*coagulation factor), present in blood plasma, that is acted upon by the enzyme thrombin to produce the insoluble protein fibrin in the final stage of *blood coagulation. The normal level of fibrinogen in plasma is 2–4 g/1 (4–6 g/l during pregnancy).... fibrinogen

n. an *anticoagulant present in the salivary glands of *leeches and in certain snake venoms that prevents *blood coagulation by inhibiting the action of the enzyme *thrombin. The anticoagulant bivalirudin is a genetically engineered form of hirudin from the medicinal leech. It is administered by intravenous injection and infusion, in combination with aspirin and clopidogrel, to treat patients with S–T elevation *myocardial infarction who are undergoing primary *percutaneous coronary intervention.... hirudin

A protein that acts as a catalyst for the body’s metabolic processes. The body contains thousands of enzymes, with each cell producing several varieties. The ?rst enzyme was obtained in a reasonably pure state in 1926. Since then, several hundred enzymes have been obtained in pure crystalline form. They are present in the digestive ?uids and in many of the tissues, and are capable of producing in small amounts the transformation on a large scale of various compounds. Examples of enzymes are found in the PTYALIN of saliva and DIASTASE of pancreatic juice which split up starch into sugar; the PEPSIN of the gastric juice and the trypsin of pancreatic juice which break proteins into simpler molecules and eventually into the constituent amino acids; and the thrombin of the blood which causes coagulation.

The diagnosis of certain disorders can be helped by measuring the concentrations of various enzymes in the blood. After a heart attack (myocardial infarction – see HEART, DISEASES OF), raised levels of heart enzymes occur as a result of damage to the cells of the heart muscle. Some inherited diseases such as GALACTOSAEMIA and PHENYLKETONURIA are the result of de?ciencies of certain enzymes.

Enzymes can be a useful part of treatment for some disorders. STREPTOKINASE, for example, is used to treat THROMBOSIS; wound-dressings containing papain from the pawpaw fruit – this contains protein-digesting enzymes – assist in the healing process; and pancreatic enzymes can be of value to patients with malabsorption caused by disorders of the PANCREAS.... enzyme

(blood clotting) the process whereby blood is converted from a liquid to a solid state. The process may be initiated by contact of blood with a foreign surface (intrinsic system) or with damaged tissue (extrinsic system). These systems involve the interaction of a variety of substances (*coagulation factors) and lead to the production of the enzyme thrombin, which converts the soluble blood protein *fibrinogen to the insoluble protein *fibrin, forming the blood clot. Finally, fibrin is broken down by the action of *plasmin. Anticoagulants and tissue plasminogen activators act by inhibiting or activating various pathways in this cascade (see illustration). Blood coagulation is an essential mechanism for the arrest of bleeding (*haemostasis). See also platelet activation.... blood coagulation

the process whereby platelets adhere to collagen released from endothelial cells in damaged blood vessels and aggregate to form a plug. An important metabolic pathway in platelets converts membrane phospholipids to *thromboxane A2 (TXA2), which can activate platelets. ADP, released from platelet granules, and *thrombin are other activators. The adhesive and aggregation reactions of platelets are mediated through surface membrane glycoproteins (Glp), Glp Ib and Glp IIb/IIIa. Aspirin acts as an *antiplatelet drug by irreversibly inhibiting one of the enzymes of this pathway, cyclo-oxygenase. Clopidrogel inhibits the ADP receptor on platelet membranes, and *abciximab blocks platelet aggregation by inhibiting Glp IIb/IIIa (see illustration overleaf).... platelet activation

(PPH) excessive bleeding (>500 ml) from the genital tract after delivery. Primary PPH occurs within 24 hours of delivery; secondary PPH occurs after 24 hours. Major (or atonic) PPH, in which blood loss exceeds 1000 ml, is due to failure of the uterus to contract after delivery. It may be caused by retained products of conception or may occur after a long labour, trauma (e.g. from cervical or vaginal tears), or thrombin deficiency. An emergency hysterectomy may be required. See also B-Lynch brace suture; Rusch catheter.... postpartum haemorrhage

(PT) the time taken for blood clotting to occur in a sample of blood to which calcium and thromboplastin have been added. A prolonged PT (compared with a control sample) indicates a deficiency of *coagulation factors, which – with calcium and thromboplastin – are required for the conversion of prothrombin to thrombin to occur in the final stages of blood coagulation. Measurement of PT is used to control anticoagulant therapy (e.g. with warfarin). See INR.... prothrombin time