Coagulation of blood

The coagulation of blood is a complex process during which blood forms solid clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel) whereby a damaged blood vessel wall is covered by a fibrin clot to stop hemorrhage and aid repair of the damaged vessel. Disorders in coagulation can lead to increased hemorrhage and/or thrombosis (formation of a clot or thrombus inside a blood vessel, obstructing the flow of blood through the circulatory system) and embolism (an embolism occurs when an object (the embolus, plural emboli) migrates from one part of the body, through circulation and cause(s) a blockage of a blood vessel in another part of the body..
In brief
In a normal individual, coagulation is initiated within 20 seconds after an injury occurs to the blood vessel damaging the endothelial cells. Platelets immediately form a haemostatic plug at the site of injury. This is called primary haemostasis. Secondary haemostasis then follows—plasma components called coagulation factors respond (in a complex cascade) to form fibrin strands which strengthen the platelet plug. Contrary to popular belief, coagulation from a cut on the skin is not initiated by air or drying out, but by platelets adhering to and activated by collagen in the blood vessel endothelium. The activated platelets then release the contents of their granules, these contain a variety of substances that stimulate further platelet activation and enhance the haemostatic process.
Testing of coagulation
Numerous tests are used to assess the function of the coagulation system:
• Common: aPTT, INR (PT), TCT, bleeding time, D-dimer
• Other: mixing test (whether an abnormality corrects if the patient's plasma is mixed with normal plasma), antiphosholipid antibodies, coagulation factor assays, genetic tests (eg. factor V Leiden, prothrombin mutation G20210A), dilute Russell viper venom test (dRVVT), platelet function tests, thromboelastography (TEG) or thromboelastometry (ROTEG).
History
Theories on the coagulation of blood have existed since antiquity. Physiologist Johannes Müller (1801-1858) described fibrin, the substance of a thrombus. Its soluble precursor, fibrinogen, was thus named by Rudolf Virchow (1821-1902), and isolated chemically by Prosper Sylvain Denis (1799-1863). Alexander Schmidt suggested that the conversion from fibrinogen to fibrin was the result of an enzymatic process, and labeled the hypothetical enzyme "thrombin" and its precursor "prothrombin". Arthus discovered in 1890 that calcium was essential in coagulation.

Platelets were identified in 1865, and their function was elucidated by Giulio Bizzozero in 1882.

The theory that thrombin was generated by the presence of tissue factor was consolidated by Paul Morawitz in 1905. At this stage, it was known that thrombokinase/thromboplastin (factor III) was released by damaged tissues, reacting with prothrombin (II), which, together with calcium (IV), formed thrombin, which converted fibrinogen into fibrin.

The remainder of the biochemical factors in the process of coagulation were largely discovered in the 20th century.

A first clue as to the actual complexity of the system of coagulation was the discovery of proaccelerin (initially and later called Factor V) by Paul Owren (1905-1990) in 1947. He also postulated that its function was the generation of accelerin (Factor VI), which later turned out to be the activated form of V (or Va); hence, VI is not now in active use.

Factor VII (also known as serum prothrombin conversion accelerator or proconvertin, precipitated by barium sulfate) was discovered in a young female patient in 1949 and 1951 by different groups.

Factor VIII turned out to be deficient in the clinically recognised but etiologically elusive hemophilia A; it was identified in the 1950s and is alternatively called antihemophilic globulin due to its capability to correct hemophilia A.

Factor IX was discovered in 1952 in a young patient with hemophilia B named Stephen Christmas (1947-1993). His deficiency was described by Dr. Rosemary Biggs and Professor R.G. MacFarlane in Oxford, UK. The factor is hence called Christmas Factor or Christmas Eve Factor. Christmas lived in Canada, and campaigned for blood transfusion safety until succumbing to transfusion-related AIDS at age 46. An alternative name for the factor is plasma thromboplastin component, given by an independent group in California.

Hageman factor, now known as factor XII, was identified in 1955 in an asymptomatic patient with a prolonged bleeding time named of John Hageman. Factor X, or Stuart-Prower factor, followed, in 1956. This protein was identified in a Ms. Audrey Prower of London, who had a lifelong bleeding tendency. In 1957, an American group identified the same factor in a Mr. Rufus Stuart. Factors XI and XIII were identified in 1953 and 1961, respectively.

The usage of Roman numerals rather than eponyms or systematic names was agreed upon during annual conferences (starting in 1955) of hemostasis experts. This committee evolved into the present-day International Committee on Thrombosis and Hemostasis (ICTH). Assignment of numerals ceased in 1963 after the naming of Factor XIII. The names Fletcher Factor and Fitzgerald Factor were given to further coagulation-related proteins, namely prekallikrein and high molecular weight kininogen respectively.

Factors III and VI are unassigned, as thromboplastin was never identified, and actually turned out to consist of ten further factors, and accelerin was found to be activated Factor V.

All mammals have an extremely closely related blood coagulation process, using a combined cellular and serine protease process. In fact, it is possible for any mammalian coagulation factor to "cleave" its equivalent target in any other mammal. The only nonmammalian animal that uses serine proteases for blood coagulation is the horseshoe crab.