Coagulation - Knowledge (XXG)

1400: 1408: 3010: 2275:(which behaves more like a platelet disorder except in severe cases), is the most common hereditary bleeding disorder and is characterized as being inherited autosomal recessive or dominant. In this disease, there is a defect in von Willebrand factor (vWF), which mediates the binding of glycoprotein Ib (GPIb) to collagen. This binding helps mediate the activation of platelets and formation of primary hemostasis. 49: 1869: 2127:, a deficiency of factor VIII, which is part of the contact activation pathway, results in an abnormally prolonged aPTT test but a normal PT test. Deficiencies of common pathway factors prothrombin, fibrinogen, FX, and FV will prolong both aPTT and PT. If an abnormal PT or aPTT is present, additional testing will occur to determine which (if any) factor is present as aberrant concentrations. 2417: 5584: 2765: 1142: 2146: 1646:. The initiation phase, mediated by the tissue factor exposure, proceeds via the classic extrinsic pathway and contributes to about 5% of thrombin production. The amplified production of thrombin occurs via the classic intrinsic pathway in the propagation phase; about 95% of thrombin generated will be during this second phase. 2708:

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

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Further, the final common pathway scheme implies that prothrombin is converted to thrombin only when acted upon by the intrinsic or extrinsic pathways, which is an oversimplification. In fact, thrombin is generated by activated platelets at the initiation of the platelet plug, which in turn promotes

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Modern coagulation pathway. Hand-drawn composite from similar drawings presented by Professor Dzung Le, MD, PhD, at UCSD Clinical Chemistry conferences on 14 and 21 October 2014. Original schema from Introduction to Hematology by Samuel I. Rapaport. 2nd ed.; Lippencott: 1987. Dr Le added the factor

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Middeldorp S, Nieuwlaat R, Baumann Kreuziger L, Coppens M, Houghton D, James AH, Lang E, Moll S, Myers T, Bhatt M, Chai-Adisaksopha C, Colunga-Lozano LE, Karam SG, Zhang Y, Wiercioch W, Schünemann HJ, Iorio A. American Society of Hematology 2023 guidelines for management of venous thromboembolism:

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All mammals have an extremely closely related blood coagulation process, using a combined cellular and serine protease process. It is possible for any mammalian coagulation factor to "cleave" its equivalent target in any other mammal. The only non-mammalian animal known to use serine proteases for

1430:(also known as the extrinsic pathway), which both lead to the same fundamental reactions that produce fibrin. It was previously thought that the two pathways of coagulation cascade were of equal importance, but it is now known that the primary pathway for the initiation of blood coagulation is the 1790:

shed from them. Calcium is also required at other points in the coagulation cascade. Calcium ions play a major role in the regulation of coagulation cascade that is paramount in the maintenance of hemostasis. Other than platelet activation, calcium ions are responsible for complete activation of

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rather than eponyms or systematic names was agreed upon during annual conferences (starting in 1955) of hemostasis experts. In 1962, consensus was achieved on the numbering of factors I–XII. This committee evolved into the present-day International Committee on Thrombosis and Hemostasis (ICTH).

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The division of coagulation in two pathways is arbitrary, originating from laboratory tests in which clotting times were measured either after the clotting was initiated by glass, the intrinsic pathway; or clotting was initiated by thromboplastin (a mix of tissue factor and phospholipids), the

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When there is an injury to a blood vessel, the endothelial cells can release various vasoconstrictor substances, such as endothelin and thromboxane, to induce the constriction of the smooth muscles in the vessel wall. This helps reduce blood flow to the site of injury and limits bleeding.

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Moroi M, Induruwa I, Farndale RW, Jung SM. Factor XIII is a newly identified binding partner for platelet collagen receptor GPVI-dimer-An interaction that may modulate fibrin crosslinking. Res Pract Thromb Haemost. 2022 Apr 24;6(3):e12697. doi: 10.1002/rth2.12697. PMID 35494504; PMCID:

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Peetermans M, Vanassche T, Liesenborghs L, Lijnen RH, Verhamme P. Bacterial pathogens activate plasminogen to breach tissue barriers and escape from innate immunity. Crit Rev Microbiol. 2016 Nov;42(6):866-82. doi: 10.3109/1040841X.2015.1080214. Epub 2015 Oct 20. PMID

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are the most commonly used. Warfarin affects the vitamin K-dependent clotting factors (II, VII, IX, X) and protein C and protein S, whereas heparin and related compounds increase the action of antithrombin on thrombin and factor Xa. A newer class of drugs, the

2320:, antithrombin deficiency, and various other genetic deficiencies or variants), particularly in younger patients with family history of thrombosis; however, thrombotic events are more likely when acquired risk factors are superimposed on the inherited state. 1217:: It is a series of enzymatic reactions that lead to the formation of a stable blood clot. The endothelial cells release substances like tissue factor, which triggers the extrinsic pathway of the coagulation cascade. This is called as "secondary hemostasis". 1585:

do not have a bleeding disorder. Instead, contact activation system seems to be more involved in inflammation, and innate immunity. Despite this, interference with the pathway may confer protection against thrombosis without a significant bleeding risk.

1497:, the most important constituent of the coagulation cascade in terms of its feedback activation roles, is released very rapidly. FVIIa circulates in a higher amount than any other activated coagulation factor. The process includes the following steps: 1785:

and prothrombinase complexes to function. Calcium mediates the binding of the complexes via the terminal gamma-carboxy residues on Factor Xa and Factor IXa to the phospholipid surfaces expressed by platelets, as well as procoagulant microparticles or

1639:. Along with the procoagulant and anticoagulant plasma proteins, normal physiologic coagulation requires the presence of two cell types for formation of coagulation complexes: cells that express tissue factor (usually extravascular) and platelets. 1231:(plasma transglutaminase; activated form of fibrin-stabilizing factor) promotes fibrin cross-linking, and subsequent stabilization of fibrin, leading to the formation of a fibrin clot (final blood clot), which temporarily seals the wound to allow 4800:

Andreescu M, Andreescu B. A Review About the Assessment of the Bleeding and Thrombosis Risk for Patients With Myeloproliferative Neoplasms Scheduled for Surgery. Cureus. 2024 Mar 12;16(3):e56008. doi: 10.7759/cureus.56008. PMID 38606222; PMCID:

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The interaction of vWF and GP1b alpha. The GP1b receptor on the surface of platelets allows the platelet to bind to vWF, which is exposed upon damage to vasculature. The vWF A1 domain (yellow) interacts with the extracellular domain of GP1ba

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Dicks AB, Moussallem E, Stanbro M, Walls J, Gandhi S, Gray BH. A Comprehensive Review of Risk Factors and Thrombophilia Evaluation in Venous Thromboembolism. J Clin Med. 2024 Jan 9;13(2):362. doi: 10.3390/jcm13020362. PMID 38256496; PMCID:

1991:, which synthesizes cAMP. cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade. 4675:

Rasmussen KL, Philips M, Tripodi A, Goetze JP. Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini-review. Eur J Haematol. 2020 Jun;104(6):519-525. doi: 10.1111/ejh.13394. Epub 2020 Feb 27. PMID

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Demoy M, Labrousse J, Grand F, Moyrand S, Tuffigo M, Lamarche S, Macchi L. Déficit en facteur XI : actualités et revue de littérature . Ann Biol Clin (Paris). 2024 Jun 5;82(2):225-236. French. doi: 10.1684/abc.2024.1884. PMID

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Immunohemostasis is the integration of immune activation into adaptive clot formation. Immunothrombosis is the pathological result of crosstalk between immunity, inflammation, and coagulation. Mediators of this process include

3624: 4710:/Dorgalaleh A, Favaloro EJ, Bahraini M, Rad F. Standardization of Prothrombin Time/International Normalized Ratio (PT/INR). Int J Lab Hematol. 2021 Feb;43(1):21-28. doi: 10.1111/ijlh.13349. Epub 2020 Sep 26. PMID 32979036. 3337: 4281:

Yong J, Toh CH. Rethinking coagulation: from enzymatic cascade and cell-based reactions to a convergent model involving innate immune activation. Blood. 2023 Dec 21;142(25):2133-2145. doi: 10.1182/blood.2023021166. PMID

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complex, which activates FX to FXa. The minor role that the contact activation pathway has in initiating blood clot formation can be illustrated by the fact that individuals with severe deficiencies of FXII, HMWK, and

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triggers a signaling cascade that results in activation of platelet integrins. Activated integrins mediate tight binding of platelets to the extracellular matrix. This process adheres platelets to the site of injury.

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starts, and these two process are together called "tertiary hemostasis". Activated platelets contract their internal actin and myosin fibrils in their cytoskeleton, which leads to shrinkage of the clot volume.

3209: 2657:(1905–1990) in 1947. He also postulated its function to be 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. 1860:) lead to the formation of PIVKAs (proteins formed in vitamin K absence), which are partially or totally non-gamma carboxylated, affecting the coagulation factors' ability to bind to phospholipid. 1446:

co-factor are activated to become active components that then catalyze the next reaction in the cascade, ultimately resulting in cross-linked fibrin. Coagulation factors are generally indicated by

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Maroney SA, Mast AE. New insights into the biology of tissue factor pathway inhibitor. J Thromb Haemost. 2015 Jun;13 Suppl 1(0 1):S200-7. doi: 10.1111/jth.12897. PMID 26149025; PMCID: PMC4604745.

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The coagulation process occurs in two phases. First is the initiation phase, which occurs in tissue-factor-expressing cells. This is followed by the propagation phase, which occurs on activated

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components (coagulation or clotting factors). The pathway in humans has been the most extensively researched and is the best understood. Disorders of coagulation can result in problems with

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Thrombin then activates other components of the coagulation cascade, including FV and FVIII (which forms a complex with FIX), and activates and releases FVIII from being bound to vWF.

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The view that the coagulation process is a "cascade" or "waterfall" was enunciated almost simultaneously by MacFarlane in the UK and by Davie and Ratnoff in the US, respectively.

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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

1852:. These drugs create a deficiency of reduced vitamin K by blocking VKORC, thereby inhibiting maturation of clotting factors. Vitamin K deficiency from other causes (e.g., in 1154:, the normal bodily process that stops bleeding. Coagulation is a part of an integrated series of haemostatic reactions, involving plasma, platelet, and vascular components. 1891:

that is activated by thrombin into activated protein C (APC). Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein

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in Oxford, UK. The factor is, hence, called Christmas Factor. Christmas lived in Canada and campaigned for blood transfusion safety until succumbing to transfusion-related

3171: 1968:(t-PA), which is synthesized and secreted by endothelium. Plasmin proteolytically cleaves fibrin into fibrin degradation products that inhibit excessive fibrin formation. 2749:. Exemplifying the close links between coagulation and inflammation, the horseshoe crab has a primitive response to injury, carried out by cells known as amoebocytes (or 6100: 3024:

Betts, J Gordon; Desaix, Peter; Johnson, Eddie; Johnson, Jody E; Korol, Oksana; Kruse, Dean; Poe, Brandon; Wise, James; Womble, Mark D; Young, Kelly A (28 July 2023).

1926:) that degrades the serine proteases: thrombin, FIXa, FXa, FXIa, and FXIIa. It is constantly active, but its adhesion to these factors is increased by the presence of 1287:

When the endothelium is damaged, the normally isolated underlying collagen is exposed to circulating platelets, which bind directly to collagen with collagen-specific

3725: 1465:, which act by cleaving downstream proteins. The exceptions are tissue factor, FV, FVIII, FXIII. Tissue factor, FV and FVIII are glycoproteins, and Factor XIII is a 5616: 4351:

Signorelli, Salvatore Santo; Oliveri Conti, Gea; Fiore, Maria; Cangiano, Federica; Zuccarello, Pietro; Gaudio, Agostino; Ferrante, Margherita (26 November 2020).

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Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev. 2003 Sep;17 Suppl 1:S1-5. doi: 10.1016/s0268-960x(03)90000-2. PMID 14697207.

3201: 4823:"Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures" 6008: 1938:(different heparinoids increase affinity to FXa, thrombin, or both). Quantitative or qualitative deficiency of antithrombin (inborn or acquired, e.g., in 2750: 2123:

If a coagulation factor is part of the contact activation or tissue factor pathway, a deficiency of that factor will affect only one of the tests: Thus

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A newer model of coagulation mechanism explains the intricate combination of cellular and biochemical events that occur during the coagulation process

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Platelet plug formation: The adhered platelets aggregate and form a temporary plug to stop bleeding. This process is often called "primary hemostasis".

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Following damage to the blood vessel, FVII leaves the circulation and comes into contact with tissue factor expressed on tissue-factor-bearing cells (

2519:). Also in clinical use are other small molecular compounds that interfere directly with the enzymatic action of particular coagulation factors (the 1876:

Several mechanisms keep platelet activation and the coagulation cascade in check. Abnormalities can lead to an increased tendency toward thrombosis:

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allows for platelets to adhere to the site of injury. Mutations in the genes associated with the glycoprotein Ib-IX-V complex are characteristic of

3057: 1832:(VKORC), reduces vitamin K back to its active form. Vitamin K epoxide reductase is pharmacologically important as a target of anticoagulant drugs 1412:

XI portion based on a paper from about year 2000. Dr. Le's similar drawings presented the development of this cascade over 6 frames, like a comic.

4023: 2379:, to reverse the effects of anticoagulants, and to treat bleeding in people with impaired coagulation factor synthesis or increased consumption. 1899:

and a phospholipid as cofactors, degrades FVa and FVIIIa. Quantitative or qualitative deficiency of either (protein C or protein S) may lead to

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1957, an American group identified the same factor in a Mr. Rufus Stuart. Factors XI and XIII were identified in 1953 and 1961, respectively.

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thrombophilia testing. Blood Adv. 2023 Nov 28;7(22):7101-7138. doi: 10.1182/bloodadvances.2023010177. PMID 37195076; PMCID: PMC10709681.

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Singh, S.; Dodt, J; Volkers, P.; Hethershaw, E.; Philippou, H.; Ivaskevicius, V.; Imhof, D.; Oldenburg, J.; Biswas, A. (5 August 2019).

2222: 2214: 1739: 1690:. Coagulation can physically trap invading microbes in blood clots. Also, some products of the coagulation system can contribute to the 4353:"Platelet-Derived Microparticles (MPs) and Thrombin Generation Velocity in Deep Vein Thrombosis (DVT): Results of a Case–Control Study" 3408: 1539:" complex, which activates FX; and so the cycle continues. ("Tenase" is a contraction of "ten" and the suffix "-ase" used for enzymes.) 5609: 4091:"New insight into the traditional model of the coagulation cascade and its regulation: illustrated review of a three-dimensional view" 2882: 6003: 3586: 5925: 5920: 4821:

Huber J, Stanworth SJ, Doree C, Fortin PM, Trivella M, Brunskill SJ, et al. (November 2019). Cochrane Haematology Group (ed.).

3371:"Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix" 1726:

are involved in the coagulation system. In addition, pathogenic bacteria may secrete agents that alter the coagulation system, e.g.

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are also used for sealing severe injuries quickly (such as in traumatic bleeding secondary to gunshot wounds). Thrombin and fibrin

5406:"Rethinking coagulation: from enzymatic cascade and cell-based reactions to a convergent model involving innate immune activation" 129:. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial 2573: 2479: 2369: 2230: 1264:

into plasmin, which promotes lysis of the fibrin clot; this restores the flow of blood in the damaged/obstructed blood vessels.

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are due to acquired states (older age, surgery, cancer, immobility). Unprovoked venous thrombosis may be related to inherited

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is generated by proteolytic cleavage of plasminogen, a plasma protein synthesized in the liver. This cleavage is catalyzed by

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Macfarlane RG (May 1964). "An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier".

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Giangrande PL (June 2003). "Six characters in search of an author: the history of the nomenclature of coagulation factors".

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The GP1b-IX receptor complex. This protein receptor complex is found on the surface of platelets, and in conjunction with

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and FXII becomes FXIIa. FXIIa converts FXI into FXIa. Factor XIa activates FIX, which with its co-factor FVIIIa form the

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The coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the

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Coagulation defects may cause hemorrhage or thrombosis, and occasionally both, depending on the nature of the defect.

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and A1 domain. This localization of platelets to the extracellular matrix promotes collagen interaction with platelet

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Anticoagulants and anti-platelet agents (together "antithrombotics") are amongst the most commonly used medications.

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are formed that crosslink the fibrin polymers that form from activated monomers. This stabilizes the fibrin network.

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

2241:; however, thrombocytosis may be associated with increased risk of either thrombosis or hemorrhage in patients with 2120:. Many analysers are capable of measuring a "derived fibrinogen" level from the graph of the Prothrombin time clot. 1295:(vWF), which is released from the endothelium and from platelets; vWF forms additional links between the platelets' 1803: 1343: 1320: 1187: 718: 239: 234: 103: 2050:(whether an abnormality corrects if the patient's plasma is mixed with normal plasma), coagulation factor assays, 1953:(TFPI) limits the action of tissue factor (TF). It also inhibits excessive TF-mediated activation of FVII and FX. 1903:(a tendency to develop thrombosis). Impaired action of Protein C (activated Protein C resistance), for example by 5998: 3423: 2668:, precipitated by barium sulfate) was discovered in a young female patient in 1949 and 1951 by different groups. 2500: 2218: 2083: 2051: 1919: 1549: 286: 4156:

Hoffman MM, Monroe DM. Rethinking the coagulation cascade. Curr Hematol Rep. 2005 Sep;4(5):391-6. PMID 16131441.

2282:, there is insufficient production of coagulation factors, possibly increasing risk of bleeding during surgery. 1895:. Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with 2206: 1070: 2553: 1389:

aid in aggregation of adjacent platelets, forming a platelet plug and thereby completing primary hemostasis).

3347: 102:, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves 4771: 2778: 5588: 2569: 188:

There are 13 traditional clotting factors, as named below, and other substances necessary for coagulation:

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Gene Mayer, Ph.D. Immunology Section of Microbiology and Immunology On-line. University of South Carolina

3587:"Primary and secondary hemostasis, regulators of coagulation, and fibrinolysis: Understanding the basics" 2288:

is the pathological development of blood clots. These clots may break free and become mobile, forming an

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Activated platelets release the contents of stored granules into the blood plasma. The granules include

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cascade, resulting in increased calcium concentration in the platelets' cytosol. The calcium activates

4881: 2116:(TCT). Measurement of the exact amount of fibrinogen present in the blood is generally done using the 1194:, activate platelets in the bloodstream, leading to attachment of platelets' membrane receptors (e.g. 5980: 5458: 5264: 5213: 4423: 3474: 2032: 1691: 1296: 1248: 1199: 939: 922: 743: 2166:

Platelet disorders are either congenital or acquired. Examples of congenital platelet disorders are

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was used in some forms of major surgery to decrease bleeding risk and the need for blood products.

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Deficiencies of fibrinogen (quantitative or qualitative) will prolong PT, aPTT, thrombin time, and

2071: 1719: 1288: 1214: 1109: 993: 893: 5633: 5535: 5386: 5288: 5237: 5186: 5132: 4993: 4917: 4195: 3567: 3233:"Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue" 2620: 1747: 1220: 1202:

proteins (e.g. von Willebrand factor) on cell membranes of damaged endothelial cells and exposed

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Required for coagulation factors to bind to phospholipids, which were formerly known as factor IV

157: 4727: 2647: 4528:"A Comprehensive Review of Risk Factors and Thrombophilia Evaluation in Venous Thromboembolism" 4050:"Contact system revisited: an interface between inflammation, coagulation, and innate immunity" 1407: 6018: 5975: 5564: 5527: 5484: 5427: 5378: 5329: 5280: 5229: 5178: 5097: 5056: 4958: 4909: 4901: 4852: 4741: 4731: 4658: 4648: 4612: 4608: 4559: 4508: 4457: 4439: 4392: 4374: 4333: 4315: 4233: 4187: 4120: 4071: 4015: 4005: 3948: 3900: 3890: 3863: 3836: 3818: 3777: 3759: 3717: 3690: 3672: 3662: 3596: 3559: 3551: 3510: 3492: 3443: 3400: 3392: 3307: 3299: 3260: 3252: 3153: 3135: 3029: 2988: 2949: 2939: 2907: 2874: 2864: 2839: 2690: 2451: 2441: 2402: 2309: 1931: 1695: 1675: 1328: 1045: 6031: 6026: 5556: 5519: 5474: 5466: 5417: 5368: 5360: 5319: 5272: 5221: 5170: 5124: 5087: 5048: 4985: 4948: 4893: 4842: 4834: 4640: 4600: 4549: 4539: 4498: 4488: 4447: 4431: 4382: 4364: 4323: 4305: 4179: 4110: 4102: 4061: 3855: 3826: 3808: 3767: 3680: 3654: 3541: 3500: 3482: 3435: 3382: 3291: 3244: 3143: 3125: 2980: 2829: 2821: 2597: 2351: 2098: 2008: 1988: 1466: 1355: 1351: 1273: 1161: 901: 756: 472:

Activates factors IX, X; increases rate of catalytic conversion of prothrombin into thrombin

4726:(8th ed.). Oxford, England; Hoboken, New Jersey: Wiley-Blackwell Publishers. pp. 3649:

Weisel, John W.; Litvinov, Rustem I. (2017). "Fibrin Formation, Structure and Properties".

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A first clue as to the actual complexity of the system of coagulation was the discovery of

2427:. The drug prevents this protein from activating the coagulation pathway by inhibiting its 6133: 5698: 5677: 5663: 5255:

Davie EW, Ratnoff OD (September 1964). "Waterfall sequence for intrinsic blood clotting".

4259: 3018: 3009: 2783: 2770: 2694: 2398: 2384: 2317: 2059: 1927: 1904: 1888: 1699: 1462: 1439: 1304: 1300: 1244: 4183: 1164:(vasospasm or vascular spasm): Here, this refers to contraction of smooth muscles in the 953:

Mediates thrombin adhesion to phospholipids and stimulates degradation of factor X by ZPI

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Hoffman M, Monroe DM (February 2007). "Coagulation 2006: a modern view of hemostasis".

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Paulus, MC; Drent, M; Kouw, IWK; Balvers, MGJ; Bast, A; van Zanten, ARH (1 July 2024).

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Decreased platelet numbers (thrombocytopenia) is due to insufficient production (e.g.,

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Various substances are required for the proper functioning of the coagulation cascade:

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The coagulation cascade of secondary hemostasis has two initial pathways which lead to

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Dicks, AB; Moussallem, E; Stanbro, M; Walls, J; Gandhi, S; Gray, BH (9 January 2024).

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Blanchette, V. S.; Brandão, L. R.; Breakey, V. R.; Revel-Vilk, S. (22 December 2016).

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pathways both activate the "final common pathway" of factor X, thrombin and fibrin.

1473:. The coagulation cascade is therefore classically divided into three pathways. The 1342:), which, in turn, activate additional platelets. The granules' contents activate a 6128: 6046: 5892: 5857: 5241: 4838: 3968: 2459: 2365: 2266: 2262: 2258: 2202:, and leads to a similar bleeding pattern; its milder forms are relatively common. 2124: 1976: 1915: 1774: 1723: 1662: 1655: 1502: 1443: 1228: 1165: 875: 638: 563: 519: 141:

formation. Platelets immediately form a plug at the site of injury; this is called

126: 48: 5276: 4252: 3463:"Von Willebrand protein binds to extracellular matrices independently of collagen" 2674:

turned out to be deficient in the clinically recognized but etiologically elusive

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Numerous medical tests are used to assess the function of the coagulation system:

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The activation of FX (to form FXa) by TF-FVIIa is almost immediately inhibited by

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Arthus M, Pagès C (1890). "Nouvelle theorie chimique de la coagulation du sang".

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Cofactor for activated protein C (APC, inactive when bound to C4b-binding protein

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Theories on the coagulation of blood have existed since antiquity. Physiologist

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Proceedings of the National Academy of Sciences of the United States of America

3439: 1868: 6112: 5816: 5778: 5738: 5733: 5723: 5560: 5364: 5349:"Structure and function of coagulogen, a clottable protein in horseshoe crabs" 4745: 3904: 3813: 2760: 2693:(1947–1993). His deficiency was described by Dr. Rosemary Biggs and Professor 2561: 2524: 2516: 2508: 2471: 2416: 2392: 2376: 2343: 2285: 2254: 2238: 2150: 2016: 1603: 1573: 1382: 1378: 1151: 816: 788: 654: 451: 223: 177: 99: 5422: 5405: 4905: 4443: 4378: 4319: 4310: 4019: 3822: 3763: 3676: 3555: 3496: 3396: 3303: 3256: 3139: 2953: 2878: 2652: 2082:

The contact activation (intrinsic) pathway is initiated by activation of the

1750:, triggering procoagulant and proinflammatory responses such as formation of 5915: 5872: 5867: 5862: 5748: 5743: 5451:

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences

5076:"Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet" 4167: 2576:

suggested that the conversion from fibrinogen to fibrin is the result of an

2504: 2475: 2410: 2112:

The quantitative and qualitative screening of fibrinogen is measured by the

1896: 1884: 1849: 1823: 1819: 1815: 1799: 1727: 1607: 1316: 1060: 946: 929: 912: 738: 734: 730: 709: 618: 535: 273: 5568: 5531: 5523: 5488: 5431: 5382: 5333: 5284: 5233: 5182: 5101: 5060: 4962: 4913: 4856: 4721: 4662: 4563: 4512: 4461: 4396: 4337: 4191: 4124: 4075: 3884: 3840: 3721: 3694: 3447: 3279: 3232: 3157: 2843: 1702:. In addition, some of the products of the coagulation system are directly 1381:. The activated platelets change shape from spherical to stellate, and the 5583: 5447:"Biochemical principle of Limulus test for detecting bacterial endotoxins" 4477:"Vitamin K: a potential missing link in critical illness-a scoping review" 3999: 3781: 3563: 3514: 3487: 3404: 3311: 3264: 2979:

Lillicrap, D.; Key, Nigel; Makris, Michael; Denise, O'Shaughnessy (2009).

2933: 2736:

Factor VI is unassigned, as accelerin was found to be activated Factor V.

2503:, is under development; some members are already in clinical use (such as 2292:

or grow to such a size that occludes the vessel in which it developed. An

6078: 5811: 5801: 5796: 4599:

David Lillicrap; Nigel Key; Michael Makris; Denise O'Shaughnessy (2009).

4369: 2593: 2581: 2557: 2536: 2532: 2491: 2487: 2305: 2301: 2297: 2293: 2289: 2106: 2024: 1837: 1833: 1807: 1778: 1660:

Eventually, blood clots are reorganized and resorbed by a process termed

1643: 1553: 1494: 1470: 1370: 1224: 1203: 1117: 722: 579: 373: 269: 169: 145:

occurs simultaneously: additional coagulation factors beyond factor VII (

111: 95: 58: 17: 5470: 5052: 4544: 3130: 1434:(extrinsic) pathway. The pathways are a series of reactions, in which a 6063: 5905: 5128: 4989: 4882:"Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP)" 2495: 2455: 2347: 2055: 2028: 1961: 1935: 1770: 1667: 1635: 1435: 165: 5594: 5039:

Shapiro SS (October 2003). "Treating thrombosis in the 21st century".

4976:

Schmidt A (1872). "Neue Untersuchungen über die Faserstoffgerinnung".

4066: 4049: 3295: 1141: 5830: 5687: 5225: 3528:

Vermylen, Jos; Verstraete, Marc; Fuster, Valentin (1 December 1986).

2825: 2577: 2428: 1923: 1782: 1622: 1577: 1536: 1505:

fibroblasts and leukocytes), forming an activated complex (TF-FVIIa).

1458: 1418: 1121: 557: 513: 173: 161: 138: 115: 87: 4089:

Troisi R, Balasco N, Autiero I, Sica F, Vitagliano L (August 2023).

3530:"Role of platelet activation and fibrin formation in thrombogenesis" 2145: 1887:

is a major physiological anticoagulant. It is a vitamin K-dependent

1710:, an amino acid produced by platelets during coagulation, can cause 1606:

to fibrin, it also activates Factors VIII and V and their inhibitor

847:

Supports reciprocal activation of factors XII, XI, and prekallikrein

149:) respond in a cascade to form fibrin strands, which strengthen the 2209:

or other bone marrow disorders), destruction by the immune system (

1493:(TF) pathway is to generate a "thrombin burst", a process by which 1130:* Vitamin K is required for biosynthesis of these clotting factors 971:

Degrades factors X (in presence of protein Z) and XI (independently

5672: 5667: 4720:

Hughes-Jones, N. C.; Wickramasinghe, S. N.; Hatton, Chris (2008).

4687:"Prothrombin Time Test and INR (PT/INR): MedlinePlus Medical Test" 3461:

Wagner, D. D.; Urban-Pickering, M.; Marder, V. J. (January 1984).

2415: 2358:

are used surgically to treat bleeding and to thrombose aneurysms.

2144: 1867: 1711: 1625:

complex until it is down-regulated by the anticoagulant pathways.

1406: 1398: 1140: 83: 3083:"Gamma-Glutamyl Carboxylase - an overview | ScienceDirect Topics" 2093:

The tissue factor (extrinsic) pathway is initiated by release of

1907:

or high levels of FVIII, also may lead to a thrombotic tendency.

5692: 4639:. Methods in Molecular Biology. Vol. 992. pp. 181–92. 2698: 2355: 1791:

several coagulation factors, including coagulation Factor XIII.

323:

Co-factor of factor VIIa, which was formerly known as factor III

164:, coagulation involves both cellular components (platelets) and 6082: 5598: 3795:

Yau, Jonathan W.; Teoh, Hwee; Verma, Subodh (19 October 2015).

679:

Intrinsic; initiates clotting in vitro; also activates plasmin

3369:

Charo, I. F.; Bekeart, L. S.; Phillips, D. R. (25 July 1987).

2596:

were identified in 1865, and their function was elucidated by

2592:

discovered in 1890 that calcium was essential in coagulation.

2097:(a specific cellular lipoprotein), and can be measured by the 1694:

by their ability to increase vascular permeability and act as

91: 5878:

Protein Z-related protease inhibitor (ZPI) (inhibits FX, FXI)

4004:(4th ed.). London: Blackwell Science. pp. 241–243. 2678:; it was identified in the 1950s and is alternatively called 1535:

FVIIIa is the co-factor of FIXa, and together they form the "

3889:(2nd ed.). Scion Publishing Limited. pp. 334–336. 3653:. Subcellular Biochemistry. Vol. 82. pp. 405–456. 3172:"Coagulation Cascade: What Is It, Steps, and More | Osmosis" 2938:. Chichester, West Sussex, UK: Wiley-Blackwell. p. 91. 1291:

surface receptors. This adhesion is strengthened further by

5708: 3536:. Symposium on Thrombosis and Antithrombotic Therapy—1986. 2615:(factor III) is released by damaged tissues, reacting with 1872:

Coagulation with arrows for negative and positive feedback.

704:

Common pathway; stabilizes fibrin; slows down fibrinolysis

121:

Coagulation begins almost instantly after an injury to the

4048:

Long AT, Kenne E, Jung R, Fuchs TA, Renné T (March 2016).

3748:"Endothelial injury, vasoconstriction, and its prevention" 1511:

FVII is itself activated by thrombin, FXIa, FXII, and FXa.

30:

This article is about blood clotting. For other uses, see

3343:

Rheumatology (6th edition) | Thromboxane A2 - an overview

2685:

Factor IX was discovered in 1952 in a young patient with

2603:

The theory that thrombin is generated by the presence of

4253:

Immunology – Chapter One: Innate (non-specific) immunity

3592:

SickKids Handbook of Pediatric Thrombosis and Hemostasis

2105:

value) to monitor dosing of oral anticoagulants such as

1856:) or impaired vitamin K metabolism in disease (e.g., in 1223:

formation: Near the end of the extrinsic pathway, after

988:

Plasminogen deficiency type I (ligneous conjunctivitis)

3998:

Hoffbrand, A. V.; Pettit, J. E; Moss, P. A. H. (2002).

2335:"Coagulant (drug)" redirects here. For other uses, see 5883:

Tissue factor pathway inhibitor (TFPI) (inhibits FIII)

5763: 2395:

is sometimes used in the treatment of major bleeding.

1983:) is released by endothelium and activates platelet G 2908:"Coagulation Factor Tests: MedlinePlus Medical Test" 2753:) which serve both hemostatic and immune functions. 2253:

The best-known coagulation factor disorders are the

985:

Converts to plasmin, lyses fibrin and other proteins

6045: 6017: 5989: 5966: 5957: 5891: 5848: 5787: 5762: 5707: 5641: 5632: 5115:Morawitz P (1905). "Die Chemie der Blutgerinnung". 4095:

Research and Practice in Thrombosis and Haemostasis

2368:is used to improve platelet function by activating 2101:(PT) test. PT results are often reported as ratio ( 1987:protein-linked receptors. This, in turn, activates 65: 41: 5949:Thrombin-activatable fibrinolysis inhibitor (TAFI) 4941:Arteriosclerosis, Thrombosis, and Vascular Biology 3617:"Coagulation Cascade: What Is It, Steps, and More" 2375:Coagulation factor concentrates are used to treat 2265:(factor IX deficiency or "Christmas disease") and 1814:residues on factors II, VII, IX and X, as well as 1666:. The main enzyme responsible for this process is 729:residues on factors II, VII, IX and X, as well as 6009:Activated protein C–protein C inhibitor (APC–PCI) 2808:Furie, Barbara C.; Furie, Bruce (December 2005). 2701:at age 46. An alternative name for the factor is 2556:(1801–1858) described fibrin, the substance of a 2194:). Most are rare. They predispose to hemorrhage. 4937:"A new generation of oral direct anticoagulants" 4880:Kaufmann, J. E.; Vischer, U. M. (1 April 2003). 2932:Schmaier, Alvin H.; Lazarus, Hillard M. (2011). 2269:(factor XI deficiency, mild bleeding tendency). 2070:(dRVVT), miscellaneous platelet function tests, 1552:begins with formation of the primary complex on 1469:. The coagulation factors circulate as inactive 1227:completes conversion of fibrinogen into fibrin, 662:Activates XI, VII, prekallikrein and plasminogen 5858:Antithrombin (inhibits FII, FIX, FX, FXI, FXII) 5010:Schmidt A. Zur Blutlehre. Leipzig: Vogel, 1892. 4232:. Oxford: Blackwell Science. pp. 243–245. 3854:Nigel Key; Michael Makris; et al. (2009). 3716:, Treasure Island (FL): StatPearls Publishing, 2705:, given by an independent group in California. 2682:due to its capability to correct hemophilia A. 2391:are commonly used coagulation factor products. 1426:(also known as the intrinsic pathway), and the 1283:Platelet activation and platelet plug formation 512:Co-factor of factor IX with which it forms the 463:Serum Prothrombin Conversion Accelerator (SPCA) 4635:Stang, LJ; Mitchell, LG (2013). "Fibrinogen". 2789:Post-vaccination embolic and thrombotic events 2580:process, and labeled the hypothetical enzyme " 2409:reduced bleeding rate. Before its withdrawal, 2362:is used to treated gastrointestinal bleeding. 1085:Inactivates tPA and urokinase (endothelial PAI 900:Inhibits factor IIa, cofactor for heparin and 393:Co-factor of factor X with which it forms the 6094: 5610: 5156: 5154: 5152: 5150: 5148: 5146: 4575: 4573: 3938: 3936: 3934: 3932: 3930: 3928: 3926: 3644: 3642: 3534:Journal of the American College of Cardiology 3338:"Chapter 23 - Inflammation and its mediators" 3231:Gordon, S. G.; Mielicki, W. P. (March 1997). 2902: 2900: 2198:is due to deficiency or abnormal function of 1104:Plasminogen activator inhibitor-1 deficiency 1088:Plasminogen activator inhibitor-1 deficiency 808:Activates XII and prekallikrein; cleaves HMWK 8: 5549:Hematology/Oncology Clinics of North America 5308:"The nomenclature of blood clotting factors" 4223: 4221: 3708:LaPelusa, Andrew; Dave, Heeransh D. (2023), 3595:. Karger Medical and Scientific Publishers. 1150:Physiology of blood coagulation is based on 883:Inhibits factors IIa, Xa, IXa, XIa, and XIIa 748:Phytyl-substituted naphthoquinone derivative 4978:Pflügers Archiv für die gesamte Physiologie 4827:The Cochrane Database of Systematic Reviews 4043: 4041: 3651:Fibrous Proteins: Structures and Mechanisms 3077: 3075: 3028:. Houston: OpenStax CNX. 18.5 Homeostasis. 2233:). An increase in platelet count is called 2027:count, platelet function testing (often by 192:Coagulation factors and related substances 6101: 6087: 6079: 5963: 5638: 5617: 5603: 5595: 4168:"Remodeling the blood coagulation cascade" 2611:in 1905. At this stage, it was known that 1239:, while the clot's outer part is shed off. 1023:Inhibits plasmin, kallikrein, and thrombin 114:, as well as deposition and maturation of 47: 5926:Plasminogen activator inhibitor-2 (PAI-2) 5921:Plasminogen activator inhibitor-1 (PAI-1) 5788: 5478: 5421: 5372: 5323: 5091: 4952: 4846: 4553: 4543: 4502: 4492: 4451: 4386: 4368: 4327: 4309: 4114: 4065: 3830: 3812: 3771: 3684: 3545: 3504: 3486: 3386: 3147: 3129: 2833: 2646:(initially and later called Factor V) by 1686:The coagulation system overlaps with the 1157:Hemostasis consists of four main stages: 811:Prekallikrein/Fletcher factor deficiency 776:Binds to VIII, mediates platelet adhesion 137:, which ultimately leads to cross-linked 5642: 4772:"Disseminated Intravascular Coagulation" 4630: 4628: 4292:Palta, A.; Palta, S.; Saroa, R. (2014). 3883:Watson, M. S.; Pallister, C. J. (2010). 3797:"Endothelial cell control of thrombosis" 2863:(2nd ed.). Elsevier. pp. 3–5. 2662:serum prothrombin conversion accelerator 2568:(1821–1902), and isolated chemically by 1718:by acting as a cationic detergent. Many 301:Common pathway; converted into thrombin 190: 146: 143:primary hemostasis. Secondary hemostasis 2800: 1905:having the "Leiden" variant of Factor V 1602:Thrombin functions not only to convert 1403:The classical blood coagulation pathway 5719:High-molecular-weight kininogen (HMWK) 4172:Journal of Thrombosis and Thrombolysis 3947:. Scion Publishing. pp. 336–347. 3114:"The unexhausted potential of E. coli" 3060:from the original on 12 September 2023 2393:Recombinant activated human factor VII 2227:disseminated intravascular coagulation 1946:Tissue factor pathway inhibitor (TFPI) 1802:is an essential factor to the hepatic 1744:pathogen-associated molecular patterns 1544:Contact activation pathway (intrinsic) 1457:The coagulation factors are generally 626:Plasma thromboplastin antecedent (PTA) 255:Common pathway; converted into fibrin 38: 5404:Yong, J; Toh, CH (21 December 2023). 4886:Journal of Thrombosis and Haemostasis 4054:Journal of Thrombosis and Haemostasis 3979:from the original on 11 December 2016 3627:from the original on 8 September 2023 3411:from the original on 15 October 2023. 3182:from the original on 8 September 2023 2814:The Journal of Clinical Investigation 1454:appended to indicate an active form. 1235:until its inner part is dissolved by 550:plasma thromboplastin component (PTC) 272:, factors I, V, VII, VIII, XI, XIII, 7: 5353:Cellular and Molecular Life Sciences 5312:Canadian Medical Association Journal 4776:The Lecturio Medical Concept Library 4752:from the original on 8 February 2022 4294:"Overview of the coagulation system" 4206:from the original on 8 February 2022 4026:from the original on 8 February 2022 3911:from the original on 8 February 2022 3237:Blood Coagulation & Fibrinolysis 3112:Blount, Zachary D. (25 March 2015). 2960:from the original on 8 February 2022 1740:damage-associated molecular patterns 964:Protein Z-related protease inhibitor 695:Congenital factor XIIIa/b deficiency 6004:Thrombin–antithrombin complex (TAT) 5041:The New England Journal of Medicine 4603:Practical Hemostasis and Thrombosis 4357:Vascular Health and Risk Management 3858:Practical Hemostasis and Thrombosis 3375:The Journal of Biological Chemistry 2983:Practical Hemostasis and Thrombosis 2521:directly acting oral anticoagulants 2405:inhibit fibrinolysis and lead to a 2223:paroxysmal nocturnal hemoglobinuria 2215:thrombotic thrombocytopenic purpura 1521:FXa and its co-factor FVa form the 228:Forms fibrin threads in blood clots 57:showing the central role played by 27:Process of formation of blood clots 5911:Tissue plasminogen activator (tPA) 5868:Protein S (cofactor for protein C) 5508:"A cell-based model of hemostasis" 5506:Hoffman M, Monroe DM (June 2001). 4184:10.1023/B:THRO.0000014588.95061.28 3728:from the original on 12 March 2023 3318:from the original on 2 August 2022 3089:. 9 September 2023. Archived from 1377:, increasing its affinity to bind 1120:; linked to thrombosis in various 25: 5347:Osaki T, Kawabata S (June 2004). 4782:from the original on 12 July 2021 3422:Watson, Steve P. (1 April 2009). 3280:"Physiology of blood coagulation" 2987:. Wiley-Blackwell. pp. 1–5. 2627:, which converts fibrinogen into 2337:Coagulant (drug) (disambiguation) 2237:, which may lead to formation of 2068:dilute Russell's viper venom time 1485:Tissue factor pathway (extrinsic) 1438:(inactive enzyme precursor) of a 1243:After the fibrin clot is formed, 1094:Plasminogen activator inhibitor-2 1078:Plasminogen activator inhibitor-1 5582: 5175:10.1046/j.1365-2141.2003.04333.x 5093:10.1111/j.1365-2141.2006.06036.x 4898:10.1046/j.1538-7836.2003.00190.x 3943:Pallister CJ, Watson MS (2010). 3249:10.1097/00001721-199703000-00001 3212:from the original on 11 May 2023 3202:"VWF gene: MedlinePlus Genetics" 3013: This article incorporates 3008: 2885:from the original on 10 May 2017 2763: 2480:glycoprotein IIb/IIIa inhibitors 2370:arginine vasopressin receptor 1A 2231:heparin-induced thrombocytopenia 2088:activated partial thromboplastin 1629:Cell-based scheme of coagulation 919:Inactivates factors Va and VIIIa 717:Essential factor to the hepatic 268:Its active form (IIa) activates 5999:Prothrombin fragment 1+2 (F1+2) 5659:Platelet membrane glycoproteins 2731:high-molecular-weight kininogen 2703:plasma thromboplastin component 2381:Prothrombin complex concentrate 2211:immune thrombocytopenic purpura 1951:Tissue factor pathway inhibitor 1781:membrane) are required for the 1558:high-molecular-weight kininogen 1516:tissue factor pathway inhibitor 907:Heparin cofactor II deficiency 831:High-molecular-weight kininogen 527:Platelets and endothelial cells 5863:Protein C (inhibits FV, FVIII) 5163:British Journal of Haematology 5080:British Journal of Haematology 4839:10.1002/14651858.CD012745.pub2 3862:. Wiley-Blackwell. p. 2. 2360:Hemostatic Powder Spray TC-325 1752:neutrophil extracellular traps 1614:). By activating Factor XIII, 1508:TF-FVIIa activates FIX and FX. 604:Congenital Factor X deficiency 401:Activated protein C resistance 368:Entire process of coagulation 1: 5277:10.1126/science.145.3638.1310 4298:Indian Journal of Anaesthesia 3752:Texas Heart Institute Journal 3547:10.1016/S0735-1097(86)80002-X 3428:Current Pharmaceutical Design 3388:10.1016/S0021-9258(18)61053-1 2188:delta storage pool deficiency 2086:, and can be measured by the 1101:Inactivates tPA and urokinase 506:Antihemophilic globulin (AHG) 4645:10.1007/978-1-62703-339-8_14 4607:. Wiley-Blackwell. pp. 4532:Journal of Clinical Medicine 3801:BMC Cardiovascular Disorders 3659:10.1007/978-3-319-49674-0_13 2810:"Thrombus formation in vivo" 2613:thrombokinase/thromboplastin 2304:and often leads to ischemic 2249:Coagulation factor disorders 2176:glycoprotein Ib-IX-V complex 1966:tissue plasminogen activator 1354:, which, in turn, activates 1258:tissue plasminogen activator 1175:Activation of platelets and 1031:Tissue plasminogen activator 429:(activated form of factor V) 365:Diet, platelets, bone matrix 206:Associated genetic disorders 32:Coagulation (disambiguation) 5739:Factor XII (Hageman factor) 5653:von Willebrand factor (vWF) 5306:Wright IS (February 1962). 4166:Hoffman, M. (August 2003). 3050:"Prothrombin thrombophilia" 2935:Concise guide to hematology 2857:Michelson, Alan D. (2006). 2619:(II), which, together with 2257:. The three main forms are 2243:myeloproliferative neoplasm 2052:antiphospholipid antibodies 1934:) or the administration of 1829:Vitamin K epoxide reductase 887:Antithrombin III deficiency 597:Activates factor II, forms 503:Antihemophilic factor (AHF) 331:Damaged cells and platelets 184:List of coagulation factors 160:throughout biology. In all 53:Blood coagulation pathways 6181: 6059:-antiplasmin complex (PAP) 5774:Factor III (tissue factor) 5512:Thrombosis and Haemostasis 4954:10.1161/ATVBAHA.111.242834 4494:10.1186/s13054-024-05001-2 4436:10.1038/s41598-019-47815-z 4107:10.1016/j.rpth.2023.102160 3540:(6, Supplement 2): 2B–9B. 3440:10.2174/138161209787846702 3358:– via ScienceDirect. 2660:Factor VII (also known as 2501:direct thrombin inhibitors 2439: 2334: 2296:is said to occur when the 2261:(factor VIII deficiency), 2168:Glanzmann's thrombasthenia 1942:) leads to thrombophilia. 1804:gamma-glutamyl carboxylase 1746:, which are recognized by 1653: 1599:more platelet activation. 1550:contact activation pathway 1424:contact activation pathway 1321:platelet-activating factor 1271: 1188:platelet activating factor 1116:Pathological activator of 870:with fibronectin deposits 719:gamma-glutamyl carboxylase 556:Activates factor X, forms 240:Familial renal amyloidosis 235:Congenital afibrinogenemia 82:, is the process by which 29: 6119: 5561:10.1016/j.hoc.2006.11.004 5365:10.1007/s00018-004-3396-5 4228:Hoffbrand, A. V. (2002). 3814:10.1186/s12872-015-0124-z 2745:blood coagulation is the 2560:. Its soluble precursor, 2486:. Of the anticoagulants, 2308:of tissue. Most cases of 2219:hemolytic-uremic syndrome 2213:), or consumption (e.g., 2084:contact activation system 1920:serine protease inhibitor 1766:Calcium and phospholipids 1525:complex, which activates 1422:formation. These are the 1303:. Binding of collagen to 1129: 692:Crosslinks fibrin threads 689:Fibrin-stabilizing factor 287:Prothrombin thrombophilia 46: 5981:β-Thromboglobulin (β-TG) 5423:10.1182/blood.2023021166 5022:Arch Physiol Norm Pathol 4311:10.4103/0019-5049.144643 3973:Clotbase.bicnirrh.res.in 3710:"Physiology, Hemostasis" 3026:Anatomy & Physiology 2207:myelodysplastic syndrome 2172:Bernard–Soulier syndrome 2155:Bernard–Soulier syndrome 2011:(also used to determine 1670:, which is regulated by 1348:-linked protein receptor 1071:Quebec platelet disorder 613:Extrinsic and intrinsic 560:complex with factor VIII 411:Extrinsic and intrinsic 362:Inorganic ions in plasma 5976:Platelet factor 4 (PF4) 5873:Protein Z (inhibits FX) 5807:Prothrombin (factor II) 5445:Iwanaga, S (May 2007). 4258:21 October 2014 at the 2779:Agglutination (biology) 2680:antihemophilic globulin 2118:Clauss fibrinogen assay 2021:Clauss fibrinogen assay 1880:Protein C and Protein S 1007:Antiplasmin deficiency 629:Antihemophilic factor C 544:Antihemophilic factor B 500:Antihemophilic factor A 6032:Fibrinopeptide B (FpB) 6027:Fibrinopeptide A (FpA) 5699:Glycoprotein VI (GPVI) 5664:Glycoprotein Ib (GPIb) 5524:10.1055/s-0037-1615947 5074:Brewer DB (May 2006). 4935:Soff GA (March 2012). 2432: 2273:Von Willebrand disease 2196:Von Willebrand disease 2180:gray platelet syndrome 2158: 2114:thrombin clotting time 2058:, genetic tests (e.g. 2019:testing (often by the 1889:serine protease enzyme 1873: 1716:Gram-positive bacteria 1413: 1404: 1254:Plasminogen activators 1206:at the site of injury. 1147: 904:("minor antithrombin") 864:Mediates cell adhesion 780:von Willebrand disease 156:Coagulation is highly 135:coagulation factor VII 131:platelet tissue factor 6139:Platelet adhesiveness 5850:Anticoagulant factors 5817:Fibrinogen (factor I) 5812:Thrombin (factor IIa) 5684:Glycoprotein IIb/IIIa 5678:Glycoprotein IX (GP9) 5645:(platelet activation) 4230:Essential haematology 4001:Essential Haematology 3746:Loscalzo, J. (1995). 3488:10.1073/pnas.81.2.471 3278:Bloom, A. L. (1990). 2584:" and its precursor " 2570:Prosper Sylvain Denis 2425:coagulation factor Xa 2419: 2200:von Willebrand factor 2148: 2076:euglobulin lysis time 1871: 1682:Role in immune system 1566:FXII (Hageman factor) 1489:The main role of the 1428:tissue factor pathway 1410: 1402: 1387:glycoprotein IIb/IIIa 1375:glycoprotein IIb/IIIa 1293:von Willebrand factor 1196:glycoprotein IIb/IIIa 1182:Platelet activation: 1144: 1067:Activates plasminogen 1038:Activates plasminogen 823:Activates plasminogen 770:von Willebrand factor 667:Hereditary angioedema 601:complex with factor V 524:Plasma protein factor 477:factor VII deficiency 427:old name of factor Va 317:tissue thromboplastin 289:(Prothrombin G20210A) 6037:Fibrin monomers (FM) 5893:Fibrinolytic factors 5711:(contact activation) 5591:at Wikimedia Commons 4370:10.2147/VHRM.S236286 3969:"Coagulation Factor" 3017:available under the 2607:was consolidated by 2564:, was thus named by 2452:Anti-platelet agents 2278:In acute or chronic 2033:thrombodynamics test 1720:acute-phase proteins 1692:innate immune system 1610:(in the presence of 1590:Final common pathway 1297:glycoprotein Ib/IX/V 1237:fibrinolytic enzymes 1200:extracellular matrix 1172:(blood vessel wall). 957:Protein Z deficiency 940:Protein S deficiency 923:Protein C deficiency 851:Kininogen deficiency 744:Vitamin K deficiency 588:Stuart-Prower factor 432:accelerin (formerly) 5991:Thrombin generation 5968:Platelet activation 5959:Coagulation markers 5634:Coagulation factors 5626:Coagulation cascade 5471:10.2183/pjab.83.110 5463:2007PJAB...83..110I 5269:1964Sci...145.1310D 5263:(3638): 1310–1312. 5218:1964Natur.202..498M 5053:10.1056/NEJMe038152 4545:10.3390/jcm13020362 4428:2019NatSR...911324S 3479:1984PNAS...81..471W 3350:on 9 September 2023 3131:10.7554/eLife.05826 3093:on 9 September 2023 2635:Coagulation factors 2548:Initial discoveries 2389:fresh frozen plasma 2346:chemicals, such as 2074:(TEG or Sonoclot), 2072:thromboelastography 2066:mutation G20210A), 1748:toll-like receptors 1595:extrinsic pathway. 1450:, with a lowercase 1393:Coagulation cascade 1289:glycoprotein Ia/IIa 1215:Coagulation cascade 1184:Platelet activators 1110:Cancer procoagulant 894:Heparin cofactor II 635:Activates factor IX 328:Lipoprotein mixture 193: 110:and aggregation of 6160:Coagulation system 5831:Fibrin (factor Ia) 5643:Primary hemostasis 5129:10.1007/BF02321003 4990:10.1007/BF01612263 4416:Scientific Reports 3290:(Suppl 1): 14–29. 2433: 2429:enzymatic activity 2423:drug bound to the 2162:Platelet disorders 2159: 2090:time (aPTT) test. 1995:Medical assessment 1874: 1696:chemotactic agents 1676:plasmin inhibitors 1672:plasmin activators 1479:contact activation 1414: 1405: 1369:then modifies the 1148: 784:Blood glycoprotein 191: 6147: 6146: 6076: 6075: 6072: 6071: 6019:Fibrin generation 5844: 5843: 5764:Extrinsic pathway 5709:Intrinsic pathway 5587:Media related to 5416:(25): 2133–2145. 5359:(11): 1257–1265. 5212:(4931): 498–499. 5047:(18): 1762–1764. 4737:978-1-4051-8050-4 4654:978-1-62703-338-1 4618:978-1-4051-8460-1 4239:978-0-632-05153-3 4067:10.1111/jth.13235 4011:978-0-632-05153-3 3954:978-1-904842-39-2 3896:978-1-904842-39-2 3869:978-1-4051-8460-1 3668:978-3-319-49672-6 3602:978-3-318-03026-6 3434:(12): 1358–1372. 3381:(21): 9935–9938. 3296:10.1159/000216159 3035:978-1-947172-04-3 2994:978-1-4051-8460-1 2945:978-1-4051-9666-6 2870:978-0-08-046586-9 2820:(12): 3355–3362. 2691:Stephen Christmas 2574:Alexander Schmidt 2478:; the parenteral 2442:Antiplatelet drug 2403:aminocaproic acid 2352:hemostatic agents 2310:venous thrombosis 1932:glycosaminoglycan 1777:(constituents of 1385:cross-links with 1329:platelet factor 4 1260:(t-PA), activate 1134: 1133: 1046:hyperfibrinolysis 838:Fitzgerald factor 73: 72: 16:(Redirected from 6172: 6103: 6096: 6089: 6080: 5964: 5639: 5619: 5612: 5605: 5596: 5586: 5572: 5543: 5493: 5492: 5482: 5442: 5436: 5435: 5425: 5401: 5395: 5394: 5376: 5344: 5338: 5337: 5327: 5303: 5297: 5296: 5252: 5246: 5245: 5226:10.1038/202498a0 5201: 5195: 5194: 5158: 5141: 5140: 5112: 5106: 5105: 5095: 5071: 5065: 5064: 5036: 5030: 5029: 5017: 5011: 5008: 5002: 5001: 4973: 4967: 4966: 4956: 4932: 4926: 4925: 4877: 4871: 4867: 4861: 4860: 4850: 4833:(11): CD012745. 4818: 4812: 4808: 4802: 4798: 4792: 4791: 4789: 4787: 4768: 4762: 4761: 4759: 4757: 4717: 4711: 4708: 4702: 4701: 4699: 4697: 4683: 4677: 4673: 4667: 4666: 4632: 4623: 4622: 4606: 4596: 4590: 4587: 4581: 4577: 4568: 4567: 4557: 4547: 4523: 4517: 4516: 4506: 4496: 4472: 4466: 4465: 4455: 4407: 4401: 4400: 4390: 4372: 4348: 4342: 4341: 4331: 4313: 4289: 4283: 4279: 4273: 4269: 4263: 4250: 4244: 4243: 4225: 4216: 4215: 4213: 4211: 4163: 4157: 4154: 4148: 4144: 4138: 4135: 4129: 4128: 4118: 4086: 4080: 4079: 4069: 4045: 4036: 4035: 4033: 4031: 3995: 3989: 3988: 3986: 3984: 3965: 3959: 3958: 3940: 3921: 3920: 3918: 3916: 3880: 3874: 3873: 3861: 3851: 3845: 3844: 3834: 3816: 3792: 3786: 3785: 3775: 3743: 3737: 3736: 3735: 3733: 3705: 3699: 3698: 3688: 3646: 3637: 3636: 3634: 3632: 3613: 3607: 3606: 3582: 3576: 3575: 3549: 3525: 3519: 3518: 3508: 3490: 3458: 3452: 3451: 3419: 3413: 3412: 3390: 3366: 3360: 3359: 3357: 3355: 3346:. Archived from 3334: 3328: 3327: 3325: 3323: 3275: 3269: 3268: 3228: 3222: 3221: 3219: 3217: 3198: 3192: 3191: 3189: 3187: 3168: 3162: 3161: 3151: 3133: 3109: 3103: 3102: 3100: 3098: 3079: 3070: 3069: 3067: 3065: 3046: 3040: 3039: 3012: 3005: 2999: 2998: 2986: 2976: 2970: 2969: 2967: 2965: 2929: 2923: 2922: 2920: 2918: 2904: 2895: 2894: 2892: 2890: 2854: 2848: 2847: 2837: 2826:10.1172/JCI26987 2805: 2773: 2768: 2767: 2766: 2733:, respectively. 2656: 2598:Giulio Bizzozero 2482:are used during 2239:thromboembolisms 2099:prothrombin time 1989:adenylyl cyclase 1700:phagocytic cells 1572:is converted to 1467:transglutaminase 1463:serine proteases 1352:protein kinase C 1274:Vasoconstriction 1268:Vasoconstriction 1247:occurs and then 1162:Vasoconstriction 1004:Inhibits plasmin 902:dermatan sulfate 714:Clotting vitamin 701:Liver, platelets 670: 547:Christmas factor 408:Liver, platelets 209:Type of molecule 194: 98:. It results in 78:, also known as 51: 39: 21: 6180: 6179: 6175: 6174: 6173: 6171: 6170: 6169: 6150: 6149: 6148: 6143: 6134:Clot retraction 6115: 6107: 6077: 6068: 6058: 6041: 6013: 5985: 5953: 5943: 5934: 5887: 5840: 5783: 5766:(tissue factor) 5765: 5758: 5710: 5703: 5644: 5628: 5623: 5579: 5546: 5505: 5502: 5500:Further reading 5497: 5496: 5444: 5443: 5439: 5403: 5402: 5398: 5346: 5345: 5341: 5305: 5304: 5300: 5254: 5253: 5249: 5203: 5202: 5198: 5160: 5159: 5144: 5114: 5113: 5109: 5073: 5072: 5068: 5038: 5037: 5033: 5019: 5018: 5014: 5009: 5005: 4975: 4974: 4970: 4934: 4933: 4929: 4879: 4878: 4874: 4868: 4864: 4820: 4819: 4815: 4809: 4805: 4799: 4795: 4785: 4783: 4770: 4769: 4765: 4755: 4753: 4738: 4719: 4718: 4714: 4709: 4705: 4695: 4693: 4691:medlineplus.gov 4685: 4684: 4680: 4674: 4670: 4655: 4634: 4633: 4626: 4619: 4598: 4597: 4593: 4588: 4584: 4578: 4571: 4525: 4524: 4520: 4474: 4473: 4469: 4409: 4408: 4404: 4350: 4349: 4345: 4291: 4290: 4286: 4280: 4276: 4270: 4266: 4260:Wayback Machine 4251: 4247: 4240: 4227: 4226: 4219: 4209: 4207: 4165: 4164: 4160: 4155: 4151: 4145: 4141: 4136: 4132: 4088: 4087: 4083: 4047: 4046: 4039: 4029: 4027: 4012: 3997: 3996: 3992: 3982: 3980: 3967: 3966: 3962: 3955: 3942: 3941: 3924: 3914: 3912: 3897: 3882: 3881: 3877: 3870: 3853: 3852: 3848: 3794: 3793: 3789: 3745: 3744: 3740: 3731: 3729: 3707: 3706: 3702: 3669: 3648: 3647: 3640: 3630: 3628: 3621:www.osmosis.org 3615: 3614: 3610: 3603: 3584: 3583: 3579: 3527: 3526: 3522: 3460: 3459: 3455: 3421: 3420: 3416: 3368: 3367: 3363: 3353: 3351: 3336: 3335: 3331: 3321: 3319: 3277: 3276: 3272: 3230: 3229: 3225: 3215: 3213: 3206:medlineplus.gov 3200: 3199: 3195: 3185: 3183: 3176:www.osmosis.org 3170: 3169: 3165: 3111: 3110: 3106: 3096: 3094: 3081: 3080: 3073: 3063: 3061: 3048: 3047: 3043: 3036: 3023: 3006: 3002: 2995: 2978: 2977: 2973: 2963: 2961: 2946: 2931: 2930: 2926: 2916: 2914: 2912:medlineplus.gov 2906: 2905: 2898: 2888: 2886: 2871: 2856: 2855: 2851: 2807: 2806: 2802: 2797: 2784:Antihemorrhagic 2771:Medicine portal 2769: 2764: 2762: 2759: 2742: 2718: 2695:R.G. MacFarlane 2650: 2637: 2554:Johannes Müller 2550: 2545: 2448: 2440:Main articles: 2438: 2399:Tranexamic acid 2385:cryoprecipitate 2340: 2331: 2326: 2318:factor V Leiden 2251: 2164: 2140: 2138:Role in disease 2060:factor V Leiden 1997: 1986: 1982: 1974: 1959: 1948: 1928:heparan sulfate 1913: 1882: 1866: 1797: 1768: 1760: 1706:. For example, 1684: 1658: 1652: 1631: 1592: 1546: 1487: 1440:serine protease 1395: 1368: 1364: 1359: 1356:phospholipase A 1347: 1341: 1336: 1305:glycoprotein VI 1301:glycoprotein VI 1285: 1276: 1270: 1249:clot resolution 1245:clot retraction 1139: 1055: 1016: 997: 844: 805:Fletcher factor 792: 787:Blood vessels' 761:dietary sources 760: 754: 665: 632: 594: 553: 509: 469: 435: 428: 426: 390: 354: 320: 292: 244: 186: 86:changes from a 61: 35: 28: 23: 22: 15: 12: 11: 5: 6178: 6176: 6168: 6167: 6162: 6152: 6151: 6145: 6144: 6142: 6141: 6136: 6131: 6126: 6120: 6117: 6116: 6108: 6106: 6105: 6098: 6091: 6083: 6074: 6073: 6070: 6069: 6067: 6066: 6061: 6056: 6051: 6049: 6043: 6042: 6040: 6039: 6034: 6029: 6023: 6021: 6015: 6014: 6012: 6011: 6006: 6001: 5995: 5993: 5987: 5986: 5984: 5983: 5978: 5972: 5970: 5961: 5955: 5954: 5952: 5951: 5946: 5944:-Macroglobulin 5941: 5937: 5932: 5928: 5923: 5918: 5913: 5908: 5903: 5897: 5895: 5889: 5888: 5886: 5885: 5880: 5875: 5870: 5865: 5860: 5854: 5852: 5846: 5845: 5842: 5841: 5839: 5838: 5833: 5828: 5814: 5809: 5804: 5799: 5793: 5791: 5789:Common pathway 5785: 5784: 5782: 5781: 5776: 5770: 5768: 5760: 5759: 5757: 5756: 5751: 5746: 5741: 5736: 5731: 5726: 5721: 5715: 5713: 5705: 5704: 5702: 5701: 5696: 5690: 5681: 5675: 5670: 5655: 5649: 5647: 5636: 5630: 5629: 5624: 5622: 5621: 5614: 5607: 5599: 5593: 5592: 5578: 5577:External links 5575: 5574: 5573: 5544: 5518:(6): 958–965. 5501: 5498: 5495: 5494: 5437: 5396: 5339: 5318:(8): 373–374. 5298: 5247: 5196: 5169:(5): 703–712. 5142: 5117:Ergebn Physiol 5107: 5086:(3): 251–258. 5066: 5031: 5012: 5003: 4968: 4947:(3): 569–574. 4927: 4892:(4): 682–689. 4872: 4862: 4813: 4803: 4793: 4763: 4736: 4712: 4703: 4678: 4668: 4653: 4624: 4617: 4591: 4582: 4569: 4518: 4467: 4402: 4343: 4304:(5): 515–523. 4284: 4274: 4264: 4245: 4238: 4217: 4178:(1–2): 17–20. 4158: 4149: 4139: 4130: 4081: 4060:(3): 427–437. 4037: 4010: 3990: 3960: 3953: 3922: 3895: 3875: 3868: 3846: 3787: 3758:(2): 180–184. 3738: 3700: 3667: 3638: 3608: 3601: 3577: 3520: 3473:(2): 471–475. 3453: 3414: 3361: 3329: 3270: 3223: 3193: 3163: 3104: 3071: 3041: 3034: 3000: 2993: 2971: 2944: 2924: 2896: 2869: 2849: 2799: 2798: 2796: 2793: 2792: 2791: 2786: 2781: 2775: 2774: 2758: 2755: 2747:horseshoe crab 2741: 2738: 2722:Roman numerals 2717: 2714: 2636: 2633: 2566:Rudolf Virchow 2549: 2546: 2544: 2541: 2437: 2436:Anticoagulants 2434: 2330: 2327: 2325: 2322: 2314:thrombophilias 2250: 2247: 2235:thrombocytosis 2192:dense granules 2184:alpha granules 2163: 2160: 2139: 2136: 2132:reptilase time 2080: 2079: 2036: 1996: 1993: 1984: 1980: 1973: 1970: 1958: 1955: 1947: 1944: 1912: 1909: 1893:thrombomodulin 1881: 1878: 1865: 1862: 1796: 1793: 1767: 1764: 1759: 1756: 1683: 1680: 1654:Main article: 1651: 1648: 1630: 1627: 1616:covalent bonds 1612:thrombomodulin 1591: 1588: 1545: 1542: 1541: 1540: 1533: 1530: 1523:prothrombinase 1519: 1512: 1509: 1506: 1486: 1483: 1448:Roman numerals 1394: 1391: 1366: 1362: 1357: 1345: 1339: 1334: 1284: 1281: 1272:Main article: 1269: 1266: 1241: 1240: 1218: 1212: 1211: 1210: 1207: 1192:thromboxane A2 1173: 1138: 1135: 1132: 1131: 1127: 1126: 1124: 1114: 1112: 1106: 1105: 1102: 1099: 1096: 1090: 1089: 1086: 1083: 1080: 1074: 1073: 1068: 1065: 1063: 1057: 1056: 1054: 1053: 1048: 1041: 1039: 1036: 1033: 1027: 1026: 1024: 1021: 1019: 1017:-Macroglobulin 1014: 1009: 1008: 1005: 1002: 1000: 995: 990: 989: 986: 983: 981: 975: 974: 972: 969: 966: 960: 959: 954: 951: 949: 943: 942: 937: 934: 932: 926: 925: 920: 917: 915: 909: 908: 905: 898: 896: 890: 889: 884: 881: 879: 872: 871: 868:Glomerulopathy 865: 862: 860: 854: 853: 848: 845: 843: 842: 839: 835: 833: 827: 826: 824: 821: 819: 813: 812: 809: 806: 803: 797: 796: 794: 785: 782: 777: 774: 772: 766: 765: 762: 752:Gut microbiota 749: 746: 741: 715: 712: 706: 705: 702: 699: 698:Plasma protein 696: 693: 690: 687: 681: 680: 677: 674: 673:Plasma protein 671: 663: 660: 659:Hageman factor 657: 651: 650: 647: 644: 643:Plasma protein 641: 636: 633: 631: 630: 627: 623: 621: 615: 614: 611: 608: 605: 602: 599:prothrombinase 595: 593: 592: 589: 585: 583: 576: 575: 572: 569: 568:Plasma protein 566: 561: 554: 552: 551: 548: 545: 541: 539: 532: 531: 528: 525: 522: 517: 510: 508: 507: 504: 501: 497: 495: 489: 488: 485: 482: 481:Plasma protein 479: 473: 470: 468: 467: 464: 461: 457: 455: 448: 447: 445: 442: 439: 436: 434: 433: 430: 419: 417: 413: 412: 409: 406: 405:Plasma protein 403: 398: 395:prothrombinase 391: 389: 388: 385: 382: 378: 376: 370: 369: 366: 363: 360: 358: 355: 353: 352: 349: 346: 342: 340: 336: 335: 332: 329: 326: 324: 321: 319: 318: 315: 309: 307: 303: 302: 299: 296: 295:Plasma protein 293: 291: 290: 284: 278: 276: 266: 261: 257: 256: 253: 250: 248:Plasma protein 245: 243: 242: 237: 231: 229: 226: 221: 217: 216: 213: 210: 207: 204: 201: 198: 185: 182: 71: 70: 67: 63: 62: 52: 44: 43: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 6177: 6166: 6163: 6161: 6158: 6157: 6155: 6140: 6137: 6135: 6132: 6130: 6127: 6125: 6122: 6121: 6118: 6114: 6111: 6104: 6099: 6097: 6092: 6090: 6085: 6084: 6081: 6065: 6062: 6060: 6053: 6052: 6050: 6048: 6044: 6038: 6035: 6033: 6030: 6028: 6025: 6024: 6022: 6020: 6016: 6010: 6007: 6005: 6002: 6000: 5997: 5996: 5994: 5992: 5988: 5982: 5979: 5977: 5974: 5973: 5971: 5969: 5965: 5962: 5960: 5956: 5950: 5947: 5945: 5938: 5936: 5929: 5927: 5924: 5922: 5919: 5917: 5914: 5912: 5909: 5907: 5904: 5902: 5899: 5898: 5896: 5894: 5890: 5884: 5881: 5879: 5876: 5874: 5871: 5869: 5866: 5864: 5861: 5859: 5856: 5855: 5853: 5851: 5847: 5837: 5834: 5832: 5829: 5826: 5822: 5818: 5815: 5813: 5810: 5808: 5805: 5803: 5800: 5798: 5795: 5794: 5792: 5790: 5786: 5780: 5777: 5775: 5772: 5771: 5769: 5767: 5761: 5755: 5752: 5750: 5747: 5745: 5742: 5740: 5737: 5735: 5732: 5730: 5729:Prekallikrein 5727: 5725: 5722: 5720: 5717: 5716: 5714: 5712: 5706: 5700: 5697: 5694: 5691: 5689: 5685: 5682: 5679: 5676: 5674: 5671: 5669: 5665: 5662: 5660: 5656: 5654: 5651: 5650: 5648: 5646: 5640: 5637: 5635: 5631: 5627: 5620: 5615: 5613: 5608: 5606: 5601: 5600: 5597: 5590: 5585: 5581: 5580: 5576: 5570: 5566: 5562: 5558: 5554: 5550: 5545: 5541: 5537: 5533: 5529: 5525: 5521: 5517: 5513: 5509: 5504: 5503: 5499: 5490: 5486: 5481: 5476: 5472: 5468: 5464: 5460: 5456: 5452: 5448: 5441: 5438: 5433: 5429: 5424: 5419: 5415: 5411: 5407: 5400: 5397: 5392: 5388: 5384: 5380: 5375: 5370: 5366: 5362: 5358: 5354: 5350: 5343: 5340: 5335: 5331: 5326: 5321: 5317: 5313: 5309: 5302: 5299: 5294: 5290: 5286: 5282: 5278: 5274: 5270: 5266: 5262: 5258: 5251: 5248: 5243: 5239: 5235: 5231: 5227: 5223: 5219: 5215: 5211: 5207: 5200: 5197: 5192: 5188: 5184: 5180: 5176: 5172: 5168: 5164: 5157: 5155: 5153: 5151: 5149: 5147: 5143: 5138: 5134: 5130: 5126: 5122: 5118: 5111: 5108: 5103: 5099: 5094: 5089: 5085: 5081: 5077: 5070: 5067: 5062: 5058: 5054: 5050: 5046: 5042: 5035: 5032: 5027: 5023: 5016: 5013: 5007: 5004: 4999: 4995: 4991: 4987: 4983: 4979: 4972: 4969: 4964: 4960: 4955: 4950: 4946: 4942: 4938: 4931: 4928: 4923: 4919: 4915: 4911: 4907: 4903: 4899: 4895: 4891: 4887: 4883: 4876: 4873: 4866: 4863: 4858: 4854: 4849: 4844: 4840: 4836: 4832: 4828: 4824: 4817: 4814: 4807: 4804: 4797: 4794: 4781: 4777: 4773: 4767: 4764: 4751: 4747: 4743: 4739: 4733: 4729: 4725: 4724: 4716: 4713: 4707: 4704: 4692: 4688: 4682: 4679: 4672: 4669: 4664: 4660: 4656: 4650: 4646: 4642: 4638: 4631: 4629: 4625: 4620: 4614: 4610: 4605: 4604: 4595: 4592: 4586: 4583: 4576: 4574: 4570: 4565: 4561: 4556: 4551: 4546: 4541: 4537: 4533: 4529: 4522: 4519: 4514: 4510: 4505: 4500: 4495: 4490: 4486: 4482: 4481:Critical Care 4478: 4471: 4468: 4463: 4459: 4454: 4449: 4445: 4441: 4437: 4433: 4429: 4425: 4421: 4417: 4413: 4406: 4403: 4398: 4394: 4389: 4384: 4380: 4376: 4371: 4366: 4362: 4358: 4354: 4347: 4344: 4339: 4335: 4330: 4325: 4321: 4317: 4312: 4307: 4303: 4299: 4295: 4288: 4285: 4278: 4275: 4268: 4265: 4261: 4257: 4254: 4249: 4246: 4241: 4235: 4231: 4224: 4222: 4218: 4205: 4201: 4197: 4193: 4189: 4185: 4181: 4177: 4173: 4169: 4162: 4159: 4153: 4150: 4143: 4140: 4134: 4131: 4126: 4122: 4117: 4112: 4108: 4104: 4101:(6): 102160. 4100: 4096: 4092: 4085: 4082: 4077: 4073: 4068: 4063: 4059: 4055: 4051: 4044: 4042: 4038: 4025: 4021: 4017: 4013: 4007: 4003: 4002: 3994: 3991: 3978: 3974: 3970: 3964: 3961: 3956: 3950: 3946: 3939: 3937: 3935: 3933: 3931: 3929: 3927: 3923: 3910: 3906: 3902: 3898: 3892: 3888: 3887: 3879: 3876: 3871: 3865: 3860: 3859: 3850: 3847: 3842: 3838: 3833: 3828: 3824: 3820: 3815: 3810: 3806: 3802: 3798: 3791: 3788: 3783: 3779: 3774: 3769: 3765: 3761: 3757: 3753: 3749: 3742: 3739: 3727: 3723: 3719: 3715: 3711: 3704: 3701: 3696: 3692: 3687: 3682: 3678: 3674: 3670: 3664: 3660: 3656: 3652: 3645: 3643: 3639: 3626: 3622: 3618: 3612: 3609: 3604: 3598: 3594: 3593: 3588: 3581: 3578: 3573: 3569: 3565: 3561: 3557: 3553: 3548: 3543: 3539: 3535: 3531: 3524: 3521: 3516: 3512: 3507: 3502: 3498: 3494: 3489: 3484: 3480: 3476: 3472: 3468: 3464: 3457: 3454: 3449: 3445: 3441: 3437: 3433: 3429: 3425: 3418: 3415: 3410: 3406: 3402: 3398: 3394: 3389: 3384: 3380: 3376: 3372: 3365: 3362: 3349: 3345: 3344: 3339: 3333: 3330: 3317: 3313: 3309: 3305: 3301: 3297: 3293: 3289: 3285: 3281: 3274: 3271: 3266: 3262: 3258: 3254: 3250: 3246: 3242: 3238: 3234: 3227: 3224: 3211: 3207: 3203: 3197: 3194: 3181: 3177: 3173: 3167: 3164: 3159: 3155: 3150: 3145: 3141: 3137: 3132: 3127: 3123: 3119: 3115: 3108: 3105: 3092: 3088: 3087:ScienceDirect 3084: 3078: 3076: 3072: 3059: 3055: 3051: 3045: 3042: 3037: 3031: 3027: 3022: 3020: 3016: 3011: 3004: 3001: 2996: 2990: 2985: 2984: 2975: 2972: 2959: 2955: 2951: 2947: 2941: 2937: 2936: 2928: 2925: 2913: 2909: 2903: 2901: 2897: 2884: 2880: 2876: 2872: 2866: 2862: 2861: 2853: 2850: 2845: 2841: 2836: 2831: 2827: 2823: 2819: 2815: 2811: 2804: 2801: 2794: 2790: 2787: 2785: 2782: 2780: 2777: 2776: 2772: 2761: 2756: 2754: 2752: 2748: 2740:Other species 2739: 2737: 2734: 2732: 2728: 2727:prekallikrein 2723: 2720:The usage of 2715: 2713: 2710: 2706: 2704: 2700: 2696: 2692: 2688: 2683: 2681: 2677: 2673: 2669: 2667: 2663: 2658: 2654: 2649: 2645: 2640: 2634: 2632: 2630: 2626: 2622: 2618: 2614: 2610: 2609:Paul Morawitz 2606: 2605:tissue factor 2601: 2599: 2595: 2591: 2587: 2583: 2579: 2575: 2572:(1799–1863). 2571: 2567: 2563: 2559: 2555: 2547: 2542: 2540: 2538: 2534: 2530: 2526: 2522: 2518: 2514: 2510: 2506: 2502: 2497: 2493: 2490:(and related 2489: 2485: 2481: 2477: 2473: 2469: 2465: 2461: 2457: 2453: 2447: 2446:Anticoagulant 2443: 2435: 2430: 2426: 2422: 2418: 2414: 2412: 2408: 2404: 2400: 2396: 2394: 2390: 2386: 2382: 2378: 2373: 2371: 2367: 2363: 2361: 2357: 2353: 2349: 2345: 2338: 2333: 2329:Procoagulants 2328: 2323: 2321: 2319: 2315: 2311: 2307: 2303: 2299: 2295: 2291: 2287: 2283: 2281: 2280:liver failure 2276: 2274: 2270: 2268: 2264: 2260: 2256: 2248: 2246: 2244: 2240: 2236: 2232: 2228: 2224: 2220: 2216: 2212: 2208: 2203: 2201: 2197: 2193: 2189: 2185: 2181: 2177: 2173: 2169: 2161: 2156: 2152: 2147: 2143: 2137: 2135: 2133: 2128: 2126: 2121: 2119: 2115: 2110: 2108: 2104: 2100: 2096: 2095:tissue factor 2091: 2089: 2085: 2077: 2073: 2069: 2065: 2061: 2057: 2053: 2049: 2045: 2044:bleeding time 2041: 2037: 2034: 2030: 2026: 2022: 2018: 2014: 2010: 2006: 2002: 2001: 2000: 1994: 1992: 1990: 1978: 1971: 1969: 1967: 1963: 1956: 1954: 1952: 1945: 1943: 1941: 1937: 1933: 1929: 1925: 1921: 1917: 1910: 1908: 1906: 1902: 1901:thrombophilia 1898: 1894: 1890: 1886: 1879: 1877: 1870: 1863: 1861: 1859: 1858:liver failure 1855: 1854:malabsorption 1851: 1847: 1846:phenprocoumon 1843: 1842:acenocoumarol 1839: 1835: 1831: 1830: 1825: 1821: 1817: 1813: 1812:glutamic acid 1809: 1805: 1801: 1794: 1792: 1789: 1788:microvesicles 1784: 1780: 1776: 1775:phospholipids 1772: 1765: 1763: 1757: 1755: 1753: 1749: 1745: 1741: 1735: 1733: 1732:streptokinase 1729: 1725: 1721: 1717: 1713: 1709: 1705: 1704:antimicrobial 1701: 1697: 1693: 1689: 1688:immune system 1681: 1679: 1677: 1673: 1669: 1665: 1664: 1657: 1649: 1647: 1645: 1640: 1638: 1637: 1628: 1626: 1624: 1619: 1617: 1613: 1609: 1605: 1600: 1596: 1589: 1587: 1584: 1583:prekallikrein 1579: 1575: 1571: 1570:Prekallikrein 1567: 1563: 1562:prekallikrein 1559: 1555: 1551: 1543: 1538: 1534: 1531: 1528: 1524: 1520: 1517: 1513: 1510: 1507: 1504: 1500: 1499: 1498: 1496: 1492: 1491:tissue factor 1484: 1482: 1480: 1476: 1475:tissue factor 1472: 1468: 1464: 1460: 1455: 1453: 1449: 1445: 1441: 1437: 1433: 1432:tissue factor 1429: 1425: 1421: 1420: 1409: 1401: 1397: 1392: 1390: 1388: 1384: 1380: 1376: 1372: 1360: 1353: 1349: 1337: 1333:thromboxane A 1330: 1326: 1322: 1318: 1314: 1309: 1306: 1302: 1298: 1294: 1290: 1282: 1280: 1275: 1267: 1265: 1263: 1259: 1255: 1250: 1246: 1238: 1234: 1233:wound healing 1230: 1226: 1222: 1219: 1216: 1213: 1208: 1205: 1201: 1197: 1193: 1189: 1185: 1181: 1180: 1178: 1177:platelet plug 1174: 1171: 1167: 1163: 1160: 1159: 1158: 1155: 1153: 1143: 1136: 1128: 1125: 1123: 1119: 1115: 1113: 1111: 1108: 1107: 1103: 1100: 1097: 1095: 1092: 1091: 1087: 1084: 1081: 1079: 1076: 1075: 1072: 1069: 1066: 1064: 1062: 1059: 1058: 1052: 1051:Thrombophilia 1049: 1047: 1043: 1042: 1040: 1037: 1034: 1032: 1029: 1028: 1025: 1022: 1020: 1018: 1011: 1010: 1006: 1003: 1001: 999: 992: 991: 987: 984: 982: 980: 977: 976: 973: 970: 967: 965: 962: 961: 958: 955: 952: 950: 948: 945: 944: 941: 938: 935: 933: 931: 928: 927: 924: 921: 918: 916: 914: 911: 910: 906: 903: 899: 897: 895: 892: 891: 888: 885: 882: 880: 877: 874: 873: 869: 866: 863: 861: 859: 856: 855: 852: 849: 846: 840: 837: 836: 834: 832: 829: 828: 825: 822: 820: 818: 815: 814: 810: 807: 804: 802: 801:Prekallikrein 799: 798: 795: 790: 786: 783: 781: 778: 775: 773: 771: 768: 767: 763: 758: 753: 750: 747: 745: 742: 740: 736: 732: 728: 727:glutamic acid 724: 720: 716: 713: 711: 708: 707: 703: 700: 697: 694: 691: 688: 686: 683: 682: 678: 675: 672: 668: 664: 661: 658: 656: 653: 652: 648: 645: 642: 640: 637: 634: 628: 625: 624: 622: 620: 617: 616: 612: 609: 606: 603: 600: 596: 591:Stuart factor 590: 587: 586: 584: 581: 578: 577: 573: 570: 567: 565: 562: 559: 555: 549: 546: 543: 542: 540: 537: 534: 533: 529: 526: 523: 521: 518: 515: 511: 505: 502: 499: 498: 496: 494: 491: 490: 486: 483: 480: 478: 474: 471: 466:Stable factor 465: 462: 459: 458: 456: 453: 450: 449: 446: 443: 440: 437: 431: 424: 421: 420: 418: 415: 414: 410: 407: 404: 402: 399: 396: 392: 386: 384:labile factor 383: 380: 379: 377: 375: 372: 371: 367: 364: 361: 359: 356: 350: 347: 344: 343: 341: 338: 337: 333: 330: 327: 325: 322: 316: 314: 313:Tissue factor 311: 310: 308: 305: 304: 300: 297: 294: 288: 285: 283: 282:Thrombophilia 280: 279: 277: 275: 271: 267: 265: 262: 259: 258: 254: 251: 249: 246: 241: 238: 236: 233: 232: 230: 227: 225: 222: 219: 218: 214: 211: 208: 205: 202: 199: 196: 195: 189: 183: 181: 179: 175: 171: 167: 166:proteinaceous 163: 159: 154: 152: 151:platelet plug 148: 144: 140: 136: 132: 128: 125:that lines a 124: 119: 117: 113: 109: 105: 101: 97: 93: 89: 85: 81: 77: 68: 64: 60: 56: 50: 45: 40: 37: 33: 19: 6129:Fibrinolysis 6123: 6109: 6064:D-Dimer (DD) 6047:Fibrinolysis 5935:-Antiplasmin 5657: 5552: 5548: 5515: 5511: 5457:(4): 110–9. 5454: 5450: 5440: 5413: 5409: 5399: 5356: 5352: 5342: 5315: 5311: 5301: 5260: 5256: 5250: 5209: 5205: 5199: 5166: 5162: 5120: 5116: 5110: 5083: 5079: 5069: 5044: 5040: 5034: 5025: 5021: 5015: 5006: 4981: 4977: 4971: 4944: 4940: 4930: 4889: 4885: 4875: 4865: 4830: 4826: 4816: 4806: 4801:PMC11007487. 4796: 4784:. Retrieved 4775: 4766: 4754:. Retrieved 4722: 4715: 4706: 4694:. Retrieved 4690: 4681: 4671: 4636: 4602: 4594: 4585: 4580:PMC10816375. 4535: 4531: 4521: 4484: 4480: 4470: 4422:(1): 11324. 4419: 4415: 4405: 4360: 4356: 4346: 4301: 4297: 4287: 4277: 4267: 4248: 4229: 4208:. Retrieved 4175: 4171: 4161: 4152: 4142: 4133: 4098: 4094: 4084: 4057: 4053: 4028:. Retrieved 4000: 3993: 3981:. Retrieved 3972: 3963: 3944: 3913:. Retrieved 3885: 3878: 3857: 3849: 3804: 3800: 3790: 3755: 3751: 3741: 3730:, retrieved 3713: 3703: 3650: 3629:. Retrieved 3620: 3611: 3591: 3580: 3537: 3533: 3523: 3470: 3466: 3456: 3431: 3427: 3417: 3378: 3374: 3364: 3352:. Retrieved 3348:the original 3342: 3332: 3320:. Retrieved 3287: 3283: 3273: 3243:(2): 73–86. 3240: 3236: 3226: 3214:. Retrieved 3205: 3196: 3184:. Retrieved 3175: 3166: 3121: 3117: 3107: 3095:. Retrieved 3091:the original 3086: 3064:11 September 3062:. Retrieved 3053: 3044: 3025: 3007: 3003: 2982: 2974: 2962:. Retrieved 2934: 2927: 2915:. Retrieved 2911: 2887:. Retrieved 2859: 2852: 2817: 2813: 2803: 2743: 2735: 2719: 2716:Nomenclature 2711: 2707: 2702: 2687:hemophilia B 2684: 2679: 2676:hemophilia A 2670: 2666:proconvertin 2665: 2661: 2659: 2644:proaccelerin 2643: 2641: 2638: 2628: 2624: 2623:(IV), forms 2616: 2612: 2602: 2551: 2460:dipyridamole 2449: 2406: 2397: 2374: 2366:Desmopressin 2364: 2350:, and other 2341: 2332: 2324:Pharmacology 2284: 2277: 2271: 2267:hemophilia C 2263:hemophilia B 2259:hemophilia A 2252: 2204: 2165: 2141: 2129: 2125:hemophilia A 2122: 2117: 2111: 2092: 2081: 2020: 1998: 1977:Prostacyclin 1975: 1972:Prostacyclin 1960: 1949: 1916:Antithrombin 1914: 1911:Antithrombin 1883: 1875: 1836:and related 1827: 1806:that adds a 1798: 1769: 1761: 1736: 1724:inflammation 1685: 1663:fibrinolysis 1661: 1659: 1656:Fibrinolysis 1650:Fibrinolysis 1641: 1634: 1632: 1620: 1601: 1597: 1593: 1547: 1529:to thrombin. 1488: 1478: 1474: 1456: 1451: 1444:glycoprotein 1431: 1427: 1423: 1417: 1415: 1396: 1310: 1286: 1277: 1242: 1229:factor XIIIa 1166:tunica media 1156: 1149: 998:-Antiplasmin 876:Antithrombin 721:that adds a 639:Hemophilia C 564:Hemophilia B 520:Hemophilia A 460:Proconvertin 422: 381:Proaccelerin 348:Calcium ions 187: 155: 147:listed below 142: 127:blood vessel 120: 94:, forming a 79: 75: 74: 54: 36: 6124:Coagulation 6110:Coagulation 5901:Plasminogen 5836:Factor XIII 5754:Factor VIII 5589:Coagulation 5555:(1): 1–11. 5123:: 307–422. 4984:: 413–538. 4723:Haematology 4637:Haemostasis 4363:: 489–495. 4147:PMC9035508. 3945:Haematology 3886:Haematology 3284:Haemostasis 3216:8 September 3186:8 September 3097:9 September 3054:MedlinePlus 2672:Factor VIII 2651: [ 2617:prothrombin 2586:prothrombin 2529:rivaroxaban 2513:bivalirudin 2484:angioplasty 2468:clopidogrel 2464:ticlopidine 2421:Rivaroxaban 2342:The use of 2255:hemophilias 2190:(deficient 2182:(deficient 2064:prothrombin 2048:mixing test 1940:proteinuria 1708:beta-lysine 1527:prothrombin 1262:plasminogen 1221:Fibrin clot 1179:formation: 1170:endothelium 1035:t-PA or TPA 979:Plasminogen 858:Fibronectin 793:bone marrow 685:Factor XIII 493:Factor VIII 475:Congenital 387:Ac-globulin 264:Prothrombin 215:Pathway(s) 197:Number/Name 123:endothelium 76:Coagulation 42:Coagulation 6154:Categories 6113:physiology 5779:Factor VII 5734:Kallikrein 5724:Bradykinin 5028:: 739–746. 4756:8 February 4746:1058077604 4538:(2): 362. 4487:(1): 212. 4210:8 February 4030:8 February 3915:8 February 3905:1023165019 3732:15 October 3714:StatPearls 3631:15 October 3354:15 October 3322:15 October 3124:: e05826. 2964:8 February 2889:8 February 2795:References 2648:Paul Owren 2562:fibrinogen 2525:dabigatran 2517:dabigatran 2509:argatroban 2472:ticagrelor 2377:hemophilia 2286:Thrombosis 2174:(abnormal 2017:fibrinogen 1864:Regulators 1604:fibrinogen 1574:kallikrein 1383:fibrinogen 1379:fibrinogen 1256:, such as 1186:, such as 1152:hemostasis 1137:Physiology 817:Kallikrein 789:endothelia 764:Extrinsic 655:Factor XII 649:Intrinsic 574:Intrinsic 530:Intrinsic 487:Extrinsic 452:Factor VII 423:Unassigned 334:Extrinsic 306:Factor III 260:Factor II* 224:Fibrinogen 200:Synonym(s) 178:thrombosis 170:hemorrhage 104:activation 100:hemostasis 96:blood clot 69:Beneficial 6055:Plasmin-α 5916:Urokinase 5749:Factor IX 5744:Factor XI 4906:1538-7836 4811:38702892. 4676:32049377. 4444:2045-2322 4379:1176-6344 4320:0019-5049 4282:37890148. 4272:26485450. 4020:898998816 3823:1471-2261 3764:0730-2347 3677:0306-0225 3556:0735-1097 3497:0027-8424 3397:0021-9258 3304:0301-0147 3257:0957-5235 3140:2050-084X 3019:CC BY 4.0 2954:779160978 2879:909782638 2860:Platelets 2751:hemocytes 2600:in 1882. 2594:Platelets 2578:enzymatic 2505:lepirudin 2492:coumarins 2476:prasugrel 2411:aprotinin 2344:adsorbent 1897:protein S 1885:Protein C 1850:dicumarol 1838:coumarins 1824:Protein Z 1820:Protein C 1816:Protein S 1810:group to 1800:Vitamin K 1795:Vitamin K 1758:Cofactors 1728:coagulase 1644:platelets 1608:protein C 1373:membrane 1317:serotonin 1168:layer of 1061:Urokinase 1044:Familial 947:Protein Z 930:Protein S 913:Protein C 739:Protein Z 735:Protein C 731:Protein S 725:group to 710:Vitamin K 619:Factor XI 536:Factor IX 416:Factor VI 339:Factor IV 274:protein C 270:platelets 158:conserved 112:platelets 18:Coagulate 5802:Factor V 5797:Factor X 5569:17258114 5540:18681597 5532:11434702 5489:24019589 5432:37890148 5391:24537601 5383:15170505 5374:11138774 5334:14008442 5293:34111840 5285:14173416 5234:14167839 5191:22694905 5183:12780784 5137:84003009 5102:16643426 5061:14585945 4998:37273997 4963:22345595 4922:30749769 4914:12871401 4857:31778223 4780:Archived 4750:Archived 4696:28 April 4663:23546714 4564:38256496 4555:10816375 4513:38956732 4504:11218309 4462:31383913 4397:33273818 4338:25535411 4256:Archived 4204:Archived 4200:19974377 4192:14760207 4125:37727847 4116:10506138 4076:26707513 4024:Archived 3977:Archived 3909:Archived 3841:26481314 3726:archived 3722:31424847 3695:28101869 3625:Archived 3572:23789418 3448:19355974 3409:Archived 3316:Archived 3210:Archived 3180:Archived 3158:25807083 3058:Archived 3021:license. 2958:Archived 2917:27 April 2883:Archived 2844:16322780 2757:See also 2625:thrombin 2582:thrombin 2558:thrombus 2537:edoxaban 2533:apixaban 2488:warfarin 2454:include 2407:de facto 2348:zeolites 2306:necrosis 2302:ischemia 2298:thrombus 2294:embolism 2107:warfarin 2025:platelet 2003:Common: 1936:heparins 1840:such as 1834:warfarin 1808:carboxyl 1779:platelet 1714:of many 1560:(HMWK), 1554:collagen 1495:thrombin 1471:zymogens 1442:and its 1371:integrin 1225:thrombin 1204:collagen 1118:factor X 723:carboxyl 669:type III 580:Factor X 374:Factor V 220:Factor I 203:Function 174:bruising 108:adhesion 80:clotting 59:thrombin 5906:Plasmin 5480:3756735 5459:Bibcode 5325:1848865 5265:Bibcode 5257:Science 5242:4214940 5214:Bibcode 4848:6993082 4786:12 July 4453:6683118 4424:Bibcode 4388:7705281 4329:4260295 3832:4617895 3807:: 130. 3782:7647603 3686:5536120 3564:3537069 3515:6320190 3475:Bibcode 3405:2440865 3312:2083865 3265:9518049 3149:4373459 2835:1297262 2621:calcium 2543:History 2496:heparin 2456:aspirin 2316:(e.g., 2290:embolus 2186:), and 2056:D-dimer 2038:Other: 2029:PFA-100 1962:Plasmin 1957:Plasmin 1771:Calcium 1668:plasmin 1636:in vivo 1518:(TFPI). 1503:stromal 1461:called 1459:enzymes 1436:zymogen 1323:(PAF), 1146:(blue). 1122:cancers 757:E. coli 607:Protein 516:complex 397:complex 351:Ca ions 345:Calcium 162:mammals 55:in vivo 5693:GPIIIa 5567: 5538: 5530: 5487: 5477: 5430: 5389: 5381: 5371: 5332: 5322: 5291: 5283: 5240: 5232: 5206:Nature 5189: 5181: 5135: 5100: 5059: 4996: 4961: 4920: 4912: 4904: 4855: 4845: 4744: 4734: 4730:–166. 4661: 4651: 4615: 4562: 4552: 4511: 4501: 4460: 4450: 4442: 4395: 4385: 4377: 4336: 4326: 4318: 4236: 4198: 4190: 4123: 4113: 4074: 4018: 4008: 3983:20 May 3951: 3903: 3893: 3866: 3839: 3829: 3821: 3780: 3773:325239 3770: 3762: 3720: 3693: 3683: 3675: 3665: 3599: 3570: 3562: 3554: 3513: 3506:344699 3503: 3495: 3446: 3403: 3395: 3310: 3302: 3263: 3255: 3156: 3146: 3138: 3032: 2991: 2952: 2942: 2877: 2867: 2842: 2832: 2689:named 2629:fibrin 2590:Arthus 2535:, and 2494:) and 2078:(ELT). 1924:serpin 1848:, and 1783:tenase 1623:tenase 1578:tenase 1564:, and 1537:tenase 1419:fibrin 1365:). 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