Coagulation - Knowledge (XXG)

1389: 1397: 2999: 2264:(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. 38: 1858: 2116:, 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. 2406: 5573: 2754: 1131: 2135: 1635:. 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. 2697:

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

1419:(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 1779:

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

2309:, 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. 1206:: 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". 1574:

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.

1486:, 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: 1774:

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

1628:. 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. 1220:(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 4789:

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:

1980:, 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. 4664:

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

3613: 4699:/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. 3326: 4270:

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.

3198: 2646:(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. 1849:) 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. 1435:

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

1841:. 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 1143:, the normal bodily process that stops bleeding. Coagulation is a part of an integrated series of haemostatic reactions, involving plasma, platelet, and vascular components. 1880:

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

3160: 1957:(t-PA), which is synthesized and secreted by endothelium. Plasmin proteolytically cleaves fibrin into fibrin degradation products that inhibit excessive fibrin formation. 2738:. 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 6089: 3013:

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).

1915:) 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 1276:

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

3714: 1454:, 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 5605: 4340:

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.

3190: 4812:"Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures" 5997: 1927:(different heparinoids increase affinity to FXa, thrombin, or both). Quantitative or qualitative deficiency of antithrombin (inborn or acquired, e.g., in 2739: 2112:

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 (

2508:). Also in clinical use are other small molecular compounds that interfere directly with the enzymatic action of particular coagulation factors (the 1865:

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

3046: 1821:(VKORC), reduces vitamin K back to its active form. Vitamin K epoxide reductase is pharmacologically important as a target of anticoagulant drugs 1401:

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.

4012: 2368:, to reverse the effects of anticoagulants, and to treat bleeding in people with impaired coagulation factor synthesis or increased consumption. 1888:

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).

2211: 2203: 1728: 1679:. Coagulation can physically trap invading microbes in blood clots. Also, some products of the coagulation system can contribute to the 4342:"Platelet-Derived Microparticles (MPs) and Thrombin Generation Velocity in Deep Vein Thrombosis (DVT): Results of a Case–Control Study" 3397: 1528:" complex, which activates FX; and so the cycle continues. ("Tenase" is a contraction of "ten" and the suffix "-ase" used for enzymes.) 5598: 4080:"New insight into the traditional model of the coagulation cascade and its regulation: illustrated review of a three-dimensional view" 2871: 5992: 3575: 5914: 5909: 4810:

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

3360:"Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix" 1715:

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

5395:"Rethinking coagulation: from enzymatic cascade and cell-based reactions to a convergent model involving innate immune activation" 118:. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial 2562: 2468: 2358: 2219: 1253:

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.

2230:; however, thrombocytosis may be associated with increased risk of either thrombosis or hemorrhage in patients with 2109:. Many analysers are capable of measuring a "derived fibrinogen" level from the graph of the Prothrombin time clot. 1284:(vWF), which is released from the endothelium and from platelets; vWF forms additional links between the platelets' 1792: 1332: 1309: 1176: 707: 228: 223: 92: 2039:(whether an abnormality corrects if the patient's plasma is mixed with normal plasma), coagulation factor assays, 1942:(TFPI) limits the action of tissue factor (TF). It also inhibits excessive TF-mediated activation of FVII and FX. 1892:(a tendency to develop thrombosis). Impaired action of Protein C (activated Protein C resistance), for example by 5987: 3412: 2657:, precipitated by barium sulfate) was discovered in a young female patient in 1949 and 1951 by different groups. 2489: 2207: 2072: 2040: 1908: 1538: 275: 4145:

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

2271:, there is insufficient production of coagulation factors, possibly increasing risk of bleeding during surgery. 1884:. Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with 2195: 1059: 2542: 1378:

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

3336: 91:, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves 4760: 2767: 5577: 2558: 177:

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

3576:"Primary and secondary hemostasis, regulators of coagulation, and fibrinolysis: Understanding the basics" 2277:

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

1281: 1242: 1184: 1172: 1001: 758: 655: 465: 4401:"Structure functional insights into calcium binding during the activation of coagulation factor XIII A" 1660: 1339:

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

4870: 2105:(TCT). Measurement of the exact amount of fibrinogen present in the blood is generally done using the 1183:, activate platelets in the bloodstream, leading to attachment of platelets' membrane receptors (e.g. 5969: 5447: 5253: 5202: 4412: 3463: 2021: 1680: 1285: 1237: 1188: 928: 911: 732: 2155:

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

2060: 1708: 1277: 1203: 1098: 982: 882: 5622: 5524: 5375: 5277: 5226: 5175: 5121: 4982: 4906: 4184: 3556: 3222:"Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue" 2609: 1736: 1209: 1191:

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

146: 4716: 2636: 4517:"A Comprehensive Review of Risk Factors and Thrombophilia Evaluation in Venous Thromboembolism" 4039:"Contact system revisited: an interface between inflammation, coagulation, and innate immunity" 1396: 6007: 5964: 5553: 5516: 5473: 5416: 5367: 5318: 5269: 5218: 5167: 5086: 5045: 4947: 4898: 4890: 4841: 4730: 4720: 4647: 4637: 4601: 4597: 4548: 4497: 4446: 4428: 4381: 4363: 4322: 4304: 4222: 4176: 4109: 4060: 4004: 3994: 3937: 3889: 3879: 3852: 3825: 3807: 3766: 3748: 3706: 3679: 3661: 3651: 3585: 3548: 3540: 3499: 3481: 3432: 3389: 3381: 3296: 3288: 3249: 3241: 3142: 3124: 3018: 2977: 2938: 2928: 2896: 2863: 2853: 2828: 2679: 2440: 2430: 2391: 2298: 1920: 1684: 1664: 1317: 1034: 6020: 6015: 5545: 5508: 5463: 5455: 5406: 5357: 5349: 5308: 5261: 5210: 5159: 5113: 5076: 5037: 4974: 4937: 4882: 4831: 4823: 4629: 4589: 4538: 4528: 4487: 4477: 4436: 4420: 4371: 4353: 4312: 4294: 4168: 4099: 4091: 4050: 3844: 3815: 3797: 3756: 3669: 3643: 3530: 3489: 3471: 3424: 3371: 3280: 3233: 3132: 3114: 2969: 2818: 2810: 2586: 2340: 2087: 1997: 1977: 1455: 1344: 1340: 1262: 1150: 890: 745: 461:

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

4715:(8th ed.). Oxford, England; Hoboken, New Jersey: Wiley-Blackwell Publishers. pp. 3638:

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

2416:. The drug prevents this protein from activating the coagulation pathway by inhibiting its 6122: 5687: 5666: 5652: 5244:

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

4248: 3007: 2998: 2772: 2759: 2683: 2387: 2373: 2306: 2048: 1916: 1893: 1877: 1688: 1451: 1428: 1293: 1289: 1233: 4172: 1153:(vasospasm or vascular spasm): Here, this refers to contraction of smooth muscles in the 942:

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.

1462:. The coagulation cascade is therefore classically divided into three pathways. The 1331:), which, in turn, activate additional platelets. The granules' contents activate a 6117: 6035: 5881: 5846: 5230: 4827: 3957: 2448: 2354: 2255: 2251: 2247: 2191:, and leads to a similar bleeding pattern; its milder forms are relatively common. 2113: 1965: 1904: 1763: 1712: 1651: 1644: 1491: 1432: 1217: 1154: 864: 627: 552: 508: 130:

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

115: 37: 5265: 4241: 3452:"Von Willebrand protein binds to extracellular matrices independently of collagen" 2663:

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

1988:

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

3428: 1857: 6101: 5805: 5767: 5727: 5722: 5712: 5549: 5353: 5338:"Structure and function of coagulogen, a clottable protein in horseshoe crabs" 4734: 3893: 3802: 2749: 2682:(1947–1993). His deficiency was described by Dr. Rosemary Biggs and Professor 2550: 2513: 2505: 2497: 2460: 2405: 2381: 2365: 2332: 2274: 2243: 2227: 2139: 2005: 1592: 1562: 1371: 1367: 1140: 805: 777: 643: 440: 212: 166: 88: 5411: 5394: 4894: 4432: 4367: 4308: 4299: 4008: 3811: 3752: 3665: 3544: 3485: 3385: 3292: 3245: 3128: 2942: 2867: 2641: 2071:

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

1739:, triggering procoagulant and proinflammatory responses such as formation of 5904: 5861: 5856: 5851: 5737: 5732: 5440:

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

5065:"Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet" 4156: 2565:

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

2493: 2464: 2399: 2101:

The quantitative and qualitative screening of fibrinogen is measured by the

1885: 1873: 1838: 1812: 1808: 1804: 1788: 1716: 1596: 1305: 1049: 935: 918: 901: 727: 723: 719: 698: 607: 524: 262: 5557: 5520: 5512: 5477: 5420: 5371: 5322: 5273: 5222: 5171: 5090: 5049: 4951: 4902: 4845: 4710: 4651: 4552: 4501: 4450: 4385: 4326: 4180: 4113: 4064: 3873: 3829: 3710: 3683: 3436: 3268: 3221: 3146: 2832: 1691:. In addition, some of the products of the coagulation system are directly 1370:. The activated platelets change shape from spherical to stellate, and the 5572: 5436:"Biochemical principle of Limulus test for detecting bacterial endotoxins" 4466:"Vitamin K: a potential missing link in critical illness-a scoping review" 3988: 3770: 3552: 3503: 3476: 3393: 3300: 3253: 2968:

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

2922: 2725:

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

2492:, is under development; some members are already in clinical use (such as 2281:

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

6067: 5800: 5790: 5785: 4588:

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

4358: 2582: 2570: 2546: 2525: 2521: 2480: 2476: 2294: 2290: 2286: 2282: 2278: 2095: 2013: 1826: 1822: 1796: 1767: 1649:

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

1632: 1542: 1483: 1459: 1359: 1213: 1192: 1106: 711: 568: 362: 258: 158: 134:

occurs simultaneously: additional coagulation factors beyond factor VII (

100: 84: 47: 5459: 5041: 4533: 3119: 1423:(extrinsic) pathway. The pathways are a series of reactions, in which a 6052: 5894: 5117: 4978: 4871:"Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP)" 2484: 2444: 2336: 2044: 2017: 1950: 1924: 1759: 1656: 1624: 1424: 154: 5583: 5028:

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

4965:

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

4055: 4038: 3284: 1130: 5819: 5676: 5214: 3517:

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

2814: 2566: 2417: 1912: 1771: 1611: 1566: 1525: 1494:

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

1447: 1407: 1110: 546: 502: 162: 150: 127: 104: 76: 4078:

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

3519:"Role of platelet activation and fibrin formation in thrombogenesis" 2134: 1876:

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

1699:, an amino acid produced by platelets during coagulation, can cause 1595:

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

836:

Supports reciprocal activation of factors XII, XI, and prekallikrein

138:) respond in a cascade to form fibrin strands, which strengthen the 2198:

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

1482:(TF) pathway is to generate a "thrombin burst", a process by which 1119:* Vitamin K is required for biosynthesis of these clotting factors 960:

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

5661: 5656: 4709:

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

4676:"Prothrombin Time Test and INR (PT/INR): MedlinePlus Medical Test" 3450:

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

2404: 2347:

are used surgically to treat bleeding and to thrombose aneurysms.

2133: 1856: 1700: 1614:

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

1395: 1387: 1129: 72: 3072:"Gamma-Glutamyl Carboxylase - an overview | ScienceDirect Topics" 2082:

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

1896:

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

5681: 4628:. Methods in Molecular Biology. Vol. 992. pp. 181–92. 2687: 2344: 1780:

several coagulation factors, including coagulation Factor XIII.

312:

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

153:, coagulation involves both cellular components (platelets) and 6071: 5587: 3784:

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

668:

Intrinsic; initiates clotting in vitro; also activates plasmin

3358:

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

2585:

were identified in 1865, and their function was elucidated by

2581:

discovered in 1890 that calcium was essential in coagulation.

2086:(a specific cellular lipoprotein), and can be measured by the 1683:

by their ability to increase vascular permeability and act as

80: 5867:

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

3993:(4th ed.). London: Blackwell Science. pp. 241–243. 2667:; it was identified in the 1950s and is alternatively called 1524:

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

3878:(2nd ed.). Scion Publishing Limited. pp. 334–336. 3642:. Subcellular Biochemistry. Vol. 82. pp. 405–456. 3161:"Coagulation Cascade: What Is It, Steps, and More | Osmosis" 2927:. Chichester, West Sussex, UK: Wiley-Blackwell. p. 91. 1280:

surface receptors. This adhesion is strengthened further by

5697: 3525:. Symposium on Thrombosis and Antithrombotic Therapy—1986. 2604:(factor III) is released by damaged tissues, reacting with 1861:

Coagulation with arrows for negative and positive feedback.

693:

Common pathway; stabilizes fibrin; slows down fibrinolysis

110:

Coagulation begins almost instantly after an injury to the

4037:

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

3737:"Endothelial injury, vasoconstriction, and its prevention" 1500:

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

19:

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

3332:

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

2674:

Factor IX was discovered in 1952 in a young patient with

2592:

The theory that thrombin is generated by the presence of

4242:

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

3581:

SickKids Handbook of Pediatric Thrombosis and Hemostasis

2094:

value) to monitor dosing of oral anticoagulants such as

1845:) or impaired vitamin K metabolism in disease (e.g., in 1212:

formation: Near the end of the extrinsic pathway, after

977:

Plasminogen deficiency type I (ligneous conjunctivitis)

3987:

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

2324:"Coagulant (drug)" redirects here. For other uses, see 5872:

Tissue factor pathway inhibitor (TFPI) (inhibits FIII)

5752: 2384:

is sometimes used in the treatment of major bleeding.

1972:) is released by endothelium and activates platelet G 2897:"Coagulation Factor Tests: MedlinePlus Medical Test" 2742:) which serve both hemostatic and immune functions. 2242:

The best-known coagulation factor disorders are the

974:

Converts to plasmin, lyses fibrin and other proteins

6034: 6006: 5978: 5955: 5946: 5880: 5837: 5776: 5751: 5696: 5630: 5621: 5104:Morawitz P (1905). "Die Chemie der Blutgerinnung". 4084:

Research and Practice in Thrombosis and Haemostasis

2357:is used to improve platelet function by activating 2090:(PT) test. PT results are often reported as ratio ( 1976:protein-linked receptors. This, in turn, activates 54: 30: 5938:Thrombin-activatable fibrinolysis inhibitor (TAFI) 4930:Arteriosclerosis, Thrombosis, and Vascular Biology 3606:"Coagulation Cascade: What Is It, Steps, and More" 2364:Coagulation factor concentrates are used to treat 2254:(factor IX deficiency or "Christmas disease") and 1803:residues on factors II, VII, IX and X, as well as 1655:. The main enzyme responsible for this process is 718:residues on factors II, VII, IX and X, as well as 5998:Activated protein C–protein C inhibitor (APC–PCI) 2797:Furie, Barbara C.; Furie, Bruce (December 2005). 2690:at age 46. An alternative name for the factor is 2545:(1801–1858) described fibrin, the substance of a 2183:). Most are rare. They predispose to hemorrhage. 4926:"A new generation of oral direct anticoagulants" 4869:Kaufmann, J. E.; Vischer, U. M. (1 April 2003). 2921:Schmaier, Alvin H.; Lazarus, Hillard M. (2011). 2258:(factor XI deficiency, mild bleeding tendency). 2059:(dRVVT), miscellaneous platelet function tests, 1541:begins with formation of the primary complex on 1458:. The coagulation factors circulate as inactive 1216:completes conversion of fibrinogen into fibrin, 651:Activates XI, VII, prekallikrein and plasminogen 5847:Antithrombin (inhibits FII, FIX, FX, FXI, FXII) 4999:Schmidt A. Zur Blutlehre. Leipzig: Vogel, 1892. 4221:. Oxford: Blackwell Science. pp. 243–245. 3843:Nigel Key; Michael Makris; et al. (2009). 3705:, Treasure Island (FL): StatPearls Publishing, 2694:, given by an independent group in California. 2671:due to its capability to correct hemophilia A. 2380:are commonly used coagulation factor products. 1415:(also known as the intrinsic pathway), and the 1272:Platelet activation and platelet plug formation 501:Co-factor of factor IX with which it forms the 452:Serum Prothrombin Conversion Accelerator (SPCA) 4624:Stang, LJ; Mitchell, LG (2013). "Fibrinogen". 2778:Post-vaccination embolic and thrombotic events 2569:process, and labeled the hypothetical enzyme " 2398:reduced bleeding rate. Before its withdrawal, 2351:is used to treated gastrointestinal bleeding. 1074:Inactivates tPA and urokinase (endothelial PAI 889:Inhibits factor IIa, cofactor for heparin and 382:Co-factor of factor X with which it forms the 6083: 5599: 5145: 5143: 5141: 5139: 5137: 5135: 4564: 4562: 3927: 3925: 3923: 3921: 3919: 3917: 3915: 3633: 3631: 3523:Journal of the American College of Cardiology 3327:"Chapter 23 - Inflammation and its mediators" 3220:Gordon, S. G.; Mielicki, W. P. (March 1997). 2891: 2889: 2187:is due to deficiency or abnormal function of 1093:Plasminogen activator inhibitor-1 deficiency 1077:Plasminogen activator inhibitor-1 deficiency 797:Activates XII and prekallikrein; cleaves HMWK 8: 5538:Hematology/Oncology Clinics of North America 5297:"The nomenclature of blood clotting factors" 4212: 4210: 3697:LaPelusa, Andrew; Dave, Heeransh D. (2023), 3584:. Karger Medical and Scientific Publishers. 1139:Physiology of blood coagulation is based on 872:Inhibits factors IIa, Xa, IXa, XIa, and XIIa 737:Phytyl-substituted naphthoquinone derivative 4967:Pflügers Archiv für die gesamte Physiologie 4816:The Cochrane Database of Systematic Reviews 4032: 4030: 3640:Fibrous Proteins: Structures and Mechanisms 3066: 3064: 3017:. Houston: OpenStax CNX. 18.5 Homeostasis. 2222:). An increase in platelet count is called 2016:count, platelet function testing (often by 181:Coagulation factors and related substances 6090: 6076: 6068: 5952: 5627: 5606: 5592: 5584: 4157:"Remodeling the blood coagulation cascade" 2600:in 1905. At this stage, it was known that 1228:, while the clot's outer part is shed off. 1012:Inhibits plasmin, kallikrein, and thrombin 103:, as well as deposition and maturation of 36: 5915:Plasminogen activator inhibitor-2 (PAI-2) 5910:Plasminogen activator inhibitor-1 (PAI-1) 5777: 5467: 5410: 5361: 5312: 5080: 4941: 4835: 4542: 4532: 4491: 4481: 4440: 4375: 4357: 4316: 4298: 4103: 4054: 3819: 3801: 3760: 3673: 3534: 3493: 3475: 3375: 3136: 3118: 2822: 2635:(initially and later called Factor V) by 1675:The coagulation system overlaps with the 1146:Hemostasis consists of four main stages: 800:Prekallikrein/Fletcher factor deficiency 765:Binds to VIII, mediates platelet adhesion 126:, which ultimately leads to cross-linked 5631: 4761:"Disseminated Intravascular Coagulation" 4619: 4617: 4281:Palta, A.; Palta, S.; Saroa, R. (2014). 3872:Watson, M. S.; Pallister, C. J. (2010). 3786:"Endothelial cell control of thrombosis" 2852:(2nd ed.). Elsevier. pp. 3–5. 2651:serum prothrombin conversion accelerator 2557:(1821–1902), and isolated chemically by 1707:by acting as a cationic detergent. Many 290:Common pathway; converted into thrombin 179: 135: 132:primary hemostasis. Secondary hemostasis 2789: 1894:having the "Leiden" variant of Factor V 1591:Thrombin functions not only to convert 1392:The classical blood coagulation pathway 5708:High-molecular-weight kininogen (HMWK) 4161:Journal of Thrombosis and Thrombolysis 3936:. Scion Publishing. pp. 336–347. 3103:"The unexhausted potential of E. coli" 3049:from the original on 12 September 2023 2382:Recombinant activated human factor VII 2216:disseminated intravascular coagulation 1935:Tissue factor pathway inhibitor (TFPI) 1791:is an essential factor to the hepatic 1733:pathogen-associated molecular patterns 1533:Contact activation pathway (intrinsic) 1446:The coagulation factors are generally 615:Plasma thromboplastin antecedent (PTA) 244:Common pathway; converted into fibrin 27: 5393:Yong, J; Toh, CH (21 December 2023). 4875:Journal of Thrombosis and Haemostasis 4043:Journal of Thrombosis and Haemostasis 3968:from the original on 11 December 2016 3616:from the original on 8 September 2023 3400:from the original on 15 October 2023. 3171:from the original on 8 September 2023 2803:The Journal of Clinical Investigation 1443:appended to indicate an active form. 1224:until its inner part is dissolved by 539:plasma thromboplastin component (PTC) 261:, factors I, V, VII, VIII, XI, XIII, 7: 5342:Cellular and Molecular Life Sciences 5301:Canadian Medical Association Journal 4765:The Lecturio Medical Concept Library 4741:from the original on 8 February 2022 4283:"Overview of the coagulation system" 4195:from the original on 8 February 2022 4015:from the original on 8 February 2022 3900:from the original on 8 February 2022 3226:Blood Coagulation & Fibrinolysis 3101:Blount, Zachary D. (25 March 2015). 2949:from the original on 8 February 2022 1729:damage-associated molecular patterns 953:Protein Z-related protease inhibitor 684:Congenital factor XIIIa/b deficiency 5993:Thrombin–antithrombin complex (TAT) 5030:The New England Journal of Medicine 4592:Practical Hemostasis and Thrombosis 4346:Vascular Health and Risk Management 3847:Practical Hemostasis and Thrombosis 3364:The Journal of Biological Chemistry 2972:Practical Hemostasis and Thrombosis 2510:directly acting oral anticoagulants 2394:inhibit fibrinolysis and lead to a 2212:paroxysmal nocturnal hemoglobinuria 2204:thrombotic thrombocytopenic purpura 1510:FXa and its co-factor FVa form the 217:Forms fibrin threads in blood clots 46:showing the central role played by 16:Process of formation of blood clots 5900:Tissue plasminogen activator (tPA) 5857:Protein S (cofactor for protein C) 5497:"A cell-based model of hemostasis" 5495:Hoffman M, Monroe DM (June 2001). 4173:10.1023/B:THRO.0000014588.95061.28 3717:from the original on 12 March 2023 3307:from the original on 2 August 2022 3078:. 9 September 2023. Archived from 1366:, increasing its affinity to bind 1109:; linked to thrombosis in various 14: 5336:Osaki T, Kawabata S (June 2004). 4771:from the original on 12 July 2021 3411:Watson, Steve P. (1 April 2009). 3269:"Physiology of blood coagulation" 2976:. Wiley-Blackwell. pp. 1–5. 2616:, which converts fibrinogen into 2326:Coagulant (drug) (disambiguation) 2226:, which may lead to formation of 2057:dilute Russell's viper venom time 1474:Tissue factor pathway (extrinsic) 1427:(inactive enzyme precursor) of a 1232:After the fibrin clot is formed, 1083:Plasminogen activator inhibitor-2 1067:Plasminogen activator inhibitor-1 5571: 5164:10.1046/j.1365-2141.2003.04333.x 5082:10.1111/j.1365-2141.2006.06036.x 4887:10.1046/j.1538-7836.2003.00190.x 3932:Pallister CJ, Watson MS (2010). 3238:10.1097/00001721-199703000-00001 3201:from the original on 11 May 2023 3191:"VWF gene: MedlinePlus Genetics" 3002: This article incorporates 2997: 2874:from the original on 10 May 2017 2752: 2469:glycoprotein IIb/IIIa inhibitors 2359:arginine vasopressin receptor 1A 2220:heparin-induced thrombocytopenia 2077:activated partial thromboplastin 1618:Cell-based scheme of coagulation 908:Inactivates factors Va and VIIIa 706:Essential factor to the hepatic 257:Its active form (IIa) activates 5988:Prothrombin fragment 1+2 (F1+2) 5648:Platelet membrane glycoproteins 2720:high-molecular-weight kininogen 2692:plasma thromboplastin component 2370:Prothrombin complex concentrate 2200:immune thrombocytopenic purpura 1940:Tissue factor pathway inhibitor 1770:membrane) are required for the 1547:high-molecular-weight kininogen 1505:tissue factor pathway inhibitor 896:Heparin cofactor II deficiency 820:High-molecular-weight kininogen 516:Platelets and endothelial cells 5852:Protein C (inhibits FV, FVIII) 5152:British Journal of Haematology 5069:British Journal of Haematology 4828:10.1002/14651858.CD012745.pub2 3851:. Wiley-Blackwell. p. 2. 2349:Hemostatic Powder Spray TC-325 1741:neutrophil extracellular traps 1603:). By activating Factor XIII, 1497:TF-FVIIa activates FIX and FX. 593:Congenital Factor X deficiency 390:Activated protein C resistance 357:Entire process of coagulation 1: 5266:10.1126/science.145.3638.1310 4287:Indian Journal of Anaesthesia 3741:Texas Heart Institute Journal 3536:10.1016/S0735-1097(86)80002-X 3417:Current Pharmaceutical Design 3377:10.1016/S0021-9258(18)61053-1 2177:delta storage pool deficiency 2075:, and can be measured by the 1090:Inactivates tPA and urokinase 495:Antihemophilic globulin (AHG) 4634:10.1007/978-1-62703-339-8_14 4596:. Wiley-Blackwell. pp. 4521:Journal of Clinical Medicine 3790:BMC Cardiovascular Disorders 3648:10.1007/978-3-319-49674-0_13 2799:"Thrombus formation in vivo" 2602:thrombokinase/thromboplastin 2293:and often leads to ischemic 2238:Coagulation factor disorders 2165:glycoprotein Ib-IX-V complex 1955:tissue plasminogen activator 1343:, which, in turn, activates 1247:tissue plasminogen activator 1164:Activation of platelets and 1020:Tissue plasminogen activator 418:(activated form of factor V) 354:Diet, platelets, bone matrix 195:Associated genetic disorders 21:Coagulation (disambiguation) 5728:Factor XII (Hageman factor) 5642:von Willebrand factor (vWF) 5295:Wright IS (February 1962). 4155:Hoffman, M. (August 2003). 3039:"Prothrombin thrombophilia" 2924:Concise guide to hematology 2846:Michelson, Alan D. (2006). 2608:(II), which, together with 2246:. The three main forms are 2232:myeloproliferative neoplasm 2041:antiphospholipid antibodies 1923:) or the administration of 1818:Vitamin K epoxide reductase 876:Antithrombin III deficiency 586:Activates factor II, forms 492:Antihemophilic factor (AHF) 320:Damaged cells and platelets 173:List of coagulation factors 149:throughout biology. In all 42:Blood coagulation pathways 6170: 6048:-antiplasmin complex (PAP) 5763:Factor III (tissue factor) 5501:Thrombosis and Haemostasis 4943:10.1161/ATVBAHA.111.242834 4483:10.1186/s13054-024-05001-2 4425:10.1038/s41598-019-47815-z 4096:10.1016/j.rpth.2023.102160 3529:(6, Supplement 2): 2B–9B. 3429:10.2174/138161209787846702 3347:– via ScienceDirect. 2649:Factor VII (also known as 2490:direct thrombin inhibitors 2428: 2323: 2285:is said to occur when the 2250:(factor VIII deficiency), 2157:Glanzmann's thrombasthenia 1931:) leads to thrombophilia. 1793:gamma-glutamyl carboxylase 1735:, which are recognized by 1642: 1588:more platelet activation. 1539:contact activation pathway 1413:contact activation pathway 1310:platelet-activating factor 1260: 1177:platelet activating factor 1105:Pathological activator of 859:with fibronectin deposits 708:gamma-glutamyl carboxylase 545:Activates factor X, forms 229:Familial renal amyloidosis 224:Congenital afibrinogenemia 71:, is the process by which 18: 6108: 5550:10.1016/j.hoc.2006.11.004 5354:10.1007/s00018-004-3396-5 4217:Hoffbrand, A. V. (2002). 3803:10.1186/s12872-015-0124-z 2734:blood coagulation is the 2549:. Its soluble precursor, 2475:. Of the anticoagulants, 2297:of tissue. Most cases of 2208:hemolytic-uremic syndrome 2202:), or consumption (e.g., 2073:contact activation system 1909:serine protease inhibitor 1755:Calcium and phospholipids 1514:complex, which activates 1411:formation. These are the 1292:. Binding of collagen to 1118: 681:Crosslinks fibrin threads 678:Fibrin-stabilizing factor 276:Prothrombin thrombophilia 35: 5970:β-Thromboglobulin (β-TG) 5412:10.1182/blood.2023021166 5011:Arch Physiol Norm Pathol 4300:10.4103/0019-5049.144643 3962:Clotbase.bicnirrh.res.in 3699:"Physiology, Hemostasis" 3015:Anatomy & Physiology 2196:myelodysplastic syndrome 2161:Bernard–Soulier syndrome 2144:Bernard–Soulier syndrome 2000:(also used to determine 1659:, which is regulated by 1337:-linked protein receptor 1060:Quebec platelet disorder 602:Extrinsic and intrinsic 549:complex with factor VIII 400:Extrinsic and intrinsic 351:Inorganic ions in plasma 5965:Platelet factor 4 (PF4) 5862:Protein Z (inhibits FX) 5796:Prothrombin (factor II) 5434:Iwanaga, S (May 2007). 4247:21 October 2014 at the 2768:Agglutination (biology) 2669:antihemophilic globulin 2107:Clauss fibrinogen assay 2010:Clauss fibrinogen assay 1869:Protein C and Protein S 996:Antiplasmin deficiency 618:Antihemophilic factor C 533:Antihemophilic factor B 489:Antihemophilic factor A 6021:Fibrinopeptide B (FpB) 6016:Fibrinopeptide A (FpA) 5688:Glycoprotein VI (GPVI) 5653:Glycoprotein Ib (GPIb) 5513:10.1055/s-0037-1615947 5063:Brewer DB (May 2006). 4924:Soff GA (March 2012). 2421: 2262:Von Willebrand disease 2185:Von Willebrand disease 2169:gray platelet syndrome 2147: 2103:thrombin clotting time 2047:, genetic tests (e.g. 2008:testing (often by the 1878:serine protease enzyme 1862: 1705:Gram-positive bacteria 1402: 1393: 1243:Plasminogen activators 1195:at the site of injury. 1136: 893:("minor antithrombin") 853:Mediates cell adhesion 769:von Willebrand disease 145:Coagulation is highly 124:coagulation factor VII 120:platelet tissue factor 6128:Platelet adhesiveness 5839:Anticoagulant factors 5806:Fibrinogen (factor I) 5801:Thrombin (factor IIa) 5673:Glycoprotein IIb/IIIa 5667:Glycoprotein IX (GP9) 5634:(platelet activation) 4219:Essential haematology 3990:Essential Haematology 3735:Loscalzo, J. (1995). 3477:10.1073/pnas.81.2.471 3267:Bloom, A. L. (1990). 2573:" and its precursor " 2559:Prosper Sylvain Denis 2414:coagulation factor Xa 2408: 2189:von Willebrand factor 2137: 2065:euglobulin lysis time 1860: 1671:Role in immune system 1555:FXII (Hageman factor) 1478:The main role of the 1417:tissue factor pathway 1399: 1391: 1376:glycoprotein IIb/IIIa 1364:glycoprotein IIb/IIIa 1282:von Willebrand factor 1185:glycoprotein IIb/IIIa 1171:Platelet activation: 1133: 1056:Activates plasminogen 1027:Activates plasminogen 812:Activates plasminogen 759:von Willebrand factor 656:Hereditary angioedema 590:complex with factor V 513:Plasma protein factor 466:factor VII deficiency 416:old name of factor Va 306:tissue thromboplastin 278:(Prothrombin G20210A) 6026:Fibrin monomers (FM) 5882:Fibrinolytic factors 5700:(contact activation) 5580:at Wikimedia Commons 4359:10.2147/VHRM.S236286 3958:"Coagulation Factor" 3006:available under the 2596:was consolidated by 2553:, was thus named by 2441:Anti-platelet agents 2267:In acute or chronic 2022:thrombodynamics test 1709:acute-phase proteins 1681:innate immune system 1599:(in the presence of 1579:Final common pathway 1286:glycoprotein Ib/IX/V 1226:fibrinolytic enzymes 1189:extracellular matrix 1161:(blood vessel wall). 946:Protein Z deficiency 929:Protein S deficiency 912:Protein C deficiency 840:Kininogen deficiency 733:Vitamin K deficiency 577:Stuart-Prower factor 421:accelerin (formerly) 5980:Thrombin generation 5957:Platelet activation 5948:Coagulation markers 5623:Coagulation factors 5615:Coagulation cascade 5460:10.2183/pjab.83.110 5452:2007PJAB...83..110I 5258:1964Sci...145.1310D 5252:(3638): 1310–1312. 5207:1964Natur.202..498M 5042:10.1056/NEJMe038152 4534:10.3390/jcm13020362 4417:2019NatSR...911324S 3468:1984PNAS...81..471W 3339:on 9 September 2023 3120:10.7554/eLife.05826 3082:on 9 September 2023 2624:Coagulation factors 2537:Initial discoveries 2378:fresh frozen plasma 2335:chemicals, such as 2063:(TEG or Sonoclot), 2061:thromboelastography 2055:mutation G20210A), 1737:toll-like receptors 1584:extrinsic pathway. 1439:, with a lowercase 1382:Coagulation cascade 1278:glycoprotein Ia/IIa 1204:Coagulation cascade 1173:Platelet activators 1099:Cancer procoagulant 883:Heparin cofactor II 624:Activates factor IX 317:Lipoprotein mixture 182: 99:and aggregation of 6149:Coagulation system 5820:Fibrin (factor Ia) 5632:Primary hemostasis 5118:10.1007/BF02321003 4979:10.1007/BF01612263 4405:Scientific Reports 3279:(Suppl 1): 14–29. 2422: 2418:enzymatic activity 2412:drug bound to the 2151:Platelet disorders 2148: 2079:time (aPTT) test. 1984:Medical assessment 1863: 1685:chemotactic agents 1665:plasmin inhibitors 1661:plasmin activators 1468:contact activation 1403: 1394: 1358:then modifies the 1137: 773:Blood glycoprotein 180: 6136: 6135: 6065: 6064: 6061: 6060: 6008:Fibrin generation 5833: 5832: 5753:Extrinsic pathway 5698:Intrinsic pathway 5576:Media related to 5405:(25): 2133–2145. 5348:(11): 1257–1265. 5201:(4931): 498–499. 5036:(18): 1762–1764. 4726:978-1-4051-8050-4 4643:978-1-62703-338-1 4607:978-1-4051-8460-1 4228:978-0-632-05153-3 4056:10.1111/jth.13235 4000:978-0-632-05153-3 3943:978-1-904842-39-2 3885:978-1-904842-39-2 3858:978-1-4051-8460-1 3657:978-3-319-49672-6 3591:978-3-318-03026-6 3423:(12): 1358–1372. 3370:(21): 9935–9938. 3285:10.1159/000216159 3024:978-1-947172-04-3 2983:978-1-4051-8460-1 2934:978-1-4051-9666-6 2859:978-0-08-046586-9 2809:(12): 3355–3362. 2680:Stephen Christmas 2563:Alexander Schmidt 2467:; the parenteral 2431:Antiplatelet drug 2392:aminocaproic acid 2341:hemostatic agents 2299:venous thrombosis 1921:glycosaminoglycan 1766:(constituents of 1374:cross-links with 1318:platelet factor 4 1249:(t-PA), activate 1123: 1122: 1035:hyperfibrinolysis 827:Fitzgerald factor 62: 61: 6161: 6092: 6085: 6078: 6069: 5953: 5628: 5608: 5601: 5594: 5585: 5575: 5561: 5532: 5482: 5481: 5471: 5431: 5425: 5424: 5414: 5390: 5384: 5383: 5365: 5333: 5327: 5326: 5316: 5292: 5286: 5285: 5241: 5235: 5234: 5215:10.1038/202498a0 5190: 5184: 5183: 5147: 5130: 5129: 5101: 5095: 5094: 5084: 5060: 5054: 5053: 5025: 5019: 5018: 5006: 5000: 4997: 4991: 4990: 4962: 4956: 4955: 4945: 4921: 4915: 4914: 4866: 4860: 4856: 4850: 4849: 4839: 4822:(11): CD012745. 4807: 4801: 4797: 4791: 4787: 4781: 4780: 4778: 4776: 4757: 4751: 4750: 4748: 4746: 4706: 4700: 4697: 4691: 4690: 4688: 4686: 4672: 4666: 4662: 4656: 4655: 4621: 4612: 4611: 4595: 4585: 4579: 4576: 4570: 4566: 4557: 4556: 4546: 4536: 4512: 4506: 4505: 4495: 4485: 4461: 4455: 4454: 4444: 4396: 4390: 4389: 4379: 4361: 4337: 4331: 4330: 4320: 4302: 4278: 4272: 4268: 4262: 4258: 4252: 4239: 4233: 4232: 4214: 4205: 4204: 4202: 4200: 4152: 4146: 4143: 4137: 4133: 4127: 4124: 4118: 4117: 4107: 4075: 4069: 4068: 4058: 4034: 4025: 4024: 4022: 4020: 3984: 3978: 3977: 3975: 3973: 3954: 3948: 3947: 3929: 3910: 3909: 3907: 3905: 3869: 3863: 3862: 3850: 3840: 3834: 3833: 3823: 3805: 3781: 3775: 3774: 3764: 3732: 3726: 3725: 3724: 3722: 3694: 3688: 3687: 3677: 3635: 3626: 3625: 3623: 3621: 3602: 3596: 3595: 3571: 3565: 3564: 3538: 3514: 3508: 3507: 3497: 3479: 3447: 3441: 3440: 3408: 3402: 3401: 3379: 3355: 3349: 3348: 3346: 3344: 3335:. Archived from 3323: 3317: 3316: 3314: 3312: 3264: 3258: 3257: 3217: 3211: 3210: 3208: 3206: 3187: 3181: 3180: 3178: 3176: 3157: 3151: 3150: 3140: 3122: 3098: 3092: 3091: 3089: 3087: 3068: 3059: 3058: 3056: 3054: 3035: 3029: 3028: 3001: 2994: 2988: 2987: 2975: 2965: 2959: 2958: 2956: 2954: 2918: 2912: 2911: 2909: 2907: 2893: 2884: 2883: 2881: 2879: 2843: 2837: 2836: 2826: 2815:10.1172/JCI26987 2794: 2762: 2757: 2756: 2755: 2722:, respectively. 2645: 2587:Giulio Bizzozero 2471:are used during 2228:thromboembolisms 2088:prothrombin time 1978:adenylyl cyclase 1689:phagocytic cells 1561:is converted to 1456:transglutaminase 1452:serine proteases 1341:protein kinase C 1263:Vasoconstriction 1257:Vasoconstriction 1236:occurs and then 1151:Vasoconstriction 993:Inhibits plasmin 891:dermatan sulfate 703:Clotting vitamin 690:Liver, platelets 659: 536:Christmas factor 397:Liver, platelets 198:Type of molecule 183: 87:. It results in 67:, also known as 40: 28: 6169: 6168: 6164: 6163: 6162: 6160: 6159: 6158: 6139: 6138: 6137: 6132: 6123:Clot retraction 6104: 6096: 6066: 6057: 6047: 6030: 6002: 5974: 5942: 5932: 5923: 5876: 5829: 5772: 5755:(tissue factor) 5754: 5747: 5699: 5692: 5633: 5617: 5612: 5568: 5535: 5494: 5491: 5489:Further reading 5486: 5485: 5433: 5432: 5428: 5392: 5391: 5387: 5335: 5334: 5330: 5294: 5293: 5289: 5243: 5242: 5238: 5192: 5191: 5187: 5149: 5148: 5133: 5103: 5102: 5098: 5062: 5061: 5057: 5027: 5026: 5022: 5008: 5007: 5003: 4998: 4994: 4964: 4963: 4959: 4923: 4922: 4918: 4868: 4867: 4863: 4857: 4853: 4809: 4808: 4804: 4798: 4794: 4788: 4784: 4774: 4772: 4759: 4758: 4754: 4744: 4742: 4727: 4708: 4707: 4703: 4698: 4694: 4684: 4682: 4680:medlineplus.gov 4674: 4673: 4669: 4663: 4659: 4644: 4623: 4622: 4615: 4608: 4587: 4586: 4582: 4577: 4573: 4567: 4560: 4514: 4513: 4509: 4463: 4462: 4458: 4398: 4397: 4393: 4339: 4338: 4334: 4280: 4279: 4275: 4269: 4265: 4259: 4255: 4249:Wayback Machine 4240: 4236: 4229: 4216: 4215: 4208: 4198: 4196: 4154: 4153: 4149: 4144: 4140: 4134: 4130: 4125: 4121: 4077: 4076: 4072: 4036: 4035: 4028: 4018: 4016: 4001: 3986: 3985: 3981: 3971: 3969: 3956: 3955: 3951: 3944: 3931: 3930: 3913: 3903: 3901: 3886: 3871: 3870: 3866: 3859: 3842: 3841: 3837: 3783: 3782: 3778: 3734: 3733: 3729: 3720: 3718: 3696: 3695: 3691: 3658: 3637: 3636: 3629: 3619: 3617: 3610:www.osmosis.org 3604: 3603: 3599: 3592: 3573: 3572: 3568: 3516: 3515: 3511: 3449: 3448: 3444: 3410: 3409: 3405: 3357: 3356: 3352: 3342: 3340: 3325: 3324: 3320: 3310: 3308: 3266: 3265: 3261: 3219: 3218: 3214: 3204: 3202: 3195:medlineplus.gov 3189: 3188: 3184: 3174: 3172: 3165:www.osmosis.org 3159: 3158: 3154: 3100: 3099: 3095: 3085: 3083: 3070: 3069: 3062: 3052: 3050: 3037: 3036: 3032: 3025: 3012: 2995: 2991: 2984: 2967: 2966: 2962: 2952: 2950: 2935: 2920: 2919: 2915: 2905: 2903: 2901:medlineplus.gov 2895: 2894: 2887: 2877: 2875: 2860: 2845: 2844: 2840: 2796: 2795: 2791: 2786: 2773:Antihemorrhagic 2760:Medicine portal 2758: 2753: 2751: 2748: 2731: 2707: 2684:R.G. MacFarlane 2639: 2626: 2543:Johannes Müller 2539: 2534: 2437: 2429:Main articles: 2427: 2388:Tranexamic acid 2374:cryoprecipitate 2329: 2320: 2315: 2307:factor V Leiden 2240: 2153: 2129: 2127:Role in disease 2049:factor V Leiden 1986: 1975: 1971: 1963: 1948: 1937: 1917:heparan sulfate 1902: 1871: 1855: 1786: 1757: 1749: 1695:. For example, 1673: 1647: 1641: 1620: 1581: 1535: 1476: 1429:serine protease 1384: 1357: 1353: 1348: 1345:phospholipase A 1336: 1330: 1325: 1294:glycoprotein VI 1290:glycoprotein VI 1274: 1265: 1259: 1238:clot resolution 1234:clot retraction 1128: 1044: 1005: 986: 833: 794:Fletcher factor 781: 776:Blood vessels' 750:dietary sources 749: 743: 654: 621: 583: 542: 498: 458: 424: 417: 415: 379: 343: 309: 281: 233: 175: 75:changes from a 50: 24: 17: 12: 11: 5: 6167: 6165: 6157: 6156: 6151: 6141: 6140: 6134: 6133: 6131: 6130: 6125: 6120: 6115: 6109: 6106: 6105: 6097: 6095: 6094: 6087: 6080: 6072: 6063: 6062: 6059: 6058: 6056: 6055: 6050: 6045: 6040: 6038: 6032: 6031: 6029: 6028: 6023: 6018: 6012: 6010: 6004: 6003: 6001: 6000: 5995: 5990: 5984: 5982: 5976: 5975: 5973: 5972: 5967: 5961: 5959: 5950: 5944: 5943: 5941: 5940: 5935: 5933:-Macroglobulin 5930: 5926: 5921: 5917: 5912: 5907: 5902: 5897: 5892: 5886: 5884: 5878: 5877: 5875: 5874: 5869: 5864: 5859: 5854: 5849: 5843: 5841: 5835: 5834: 5831: 5830: 5828: 5827: 5822: 5817: 5803: 5798: 5793: 5788: 5782: 5780: 5778:Common pathway 5774: 5773: 5771: 5770: 5765: 5759: 5757: 5749: 5748: 5746: 5745: 5740: 5735: 5730: 5725: 5720: 5715: 5710: 5704: 5702: 5694: 5693: 5691: 5690: 5685: 5679: 5670: 5664: 5659: 5644: 5638: 5636: 5625: 5619: 5618: 5613: 5611: 5610: 5603: 5596: 5588: 5582: 5581: 5567: 5566:External links 5564: 5563: 5562: 5533: 5507:(6): 958–965. 5490: 5487: 5484: 5483: 5426: 5385: 5328: 5307:(8): 373–374. 5287: 5236: 5185: 5158:(5): 703–712. 5131: 5106:Ergebn Physiol 5096: 5075:(3): 251–258. 5055: 5020: 5001: 4992: 4957: 4936:(3): 569–574. 4916: 4881:(4): 682–689. 4861: 4851: 4802: 4792: 4782: 4752: 4725: 4701: 4692: 4667: 4657: 4642: 4613: 4606: 4580: 4571: 4558: 4507: 4456: 4391: 4332: 4293:(5): 515–523. 4273: 4263: 4253: 4234: 4227: 4206: 4167:(1–2): 17–20. 4147: 4138: 4128: 4119: 4070: 4049:(3): 427–437. 4026: 3999: 3979: 3949: 3942: 3911: 3884: 3864: 3857: 3835: 3776: 3747:(2): 180–184. 3727: 3689: 3656: 3627: 3597: 3590: 3566: 3509: 3462:(2): 471–475. 3442: 3403: 3350: 3318: 3259: 3212: 3182: 3152: 3093: 3060: 3030: 3023: 2989: 2982: 2960: 2933: 2913: 2885: 2858: 2838: 2788: 2787: 2785: 2782: 2781: 2780: 2775: 2770: 2764: 2763: 2747: 2744: 2736:horseshoe crab 2730: 2727: 2711:Roman numerals 2706: 2703: 2625: 2622: 2555:Rudolf Virchow 2538: 2535: 2533: 2530: 2426: 2425:Anticoagulants 2423: 2319: 2316: 2314: 2311: 2303:thrombophilias 2239: 2236: 2224:thrombocytosis 2181:dense granules 2173:alpha granules 2152: 2149: 2128: 2125: 2121:reptilase time 2069: 2068: 2025: 1985: 1982: 1973: 1969: 1962: 1959: 1947: 1944: 1936: 1933: 1901: 1898: 1882:thrombomodulin 1870: 1867: 1854: 1851: 1785: 1782: 1756: 1753: 1748: 1745: 1672: 1669: 1643:Main article: 1640: 1637: 1619: 1616: 1605:covalent bonds 1601:thrombomodulin 1580: 1577: 1534: 1531: 1530: 1529: 1522: 1519: 1512:prothrombinase 1508: 1501: 1498: 1495: 1475: 1472: 1437:Roman numerals 1383: 1380: 1355: 1351: 1346: 1334: 1328: 1323: 1273: 1270: 1261:Main article: 1258: 1255: 1230: 1229: 1207: 1201: 1200: 1199: 1196: 1181:thromboxane A2 1162: 1127: 1124: 1121: 1120: 1116: 1115: 1113: 1103: 1101: 1095: 1094: 1091: 1088: 1085: 1079: 1078: 1075: 1072: 1069: 1063: 1062: 1057: 1054: 1052: 1046: 1045: 1043: 1042: 1037: 1030: 1028: 1025: 1022: 1016: 1015: 1013: 1010: 1008: 1006:-Macroglobulin 1003: 998: 997: 994: 991: 989: 984: 979: 978: 975: 972: 970: 964: 963: 961: 958: 955: 949: 948: 943: 940: 938: 932: 931: 926: 923: 921: 915: 914: 909: 906: 904: 898: 897: 894: 887: 885: 879: 878: 873: 870: 868: 861: 860: 857:Glomerulopathy 854: 851: 849: 843: 842: 837: 834: 832: 831: 828: 824: 822: 816: 815: 813: 810: 808: 802: 801: 798: 795: 792: 786: 785: 783: 774: 771: 766: 763: 761: 755: 754: 751: 741:Gut microbiota 738: 735: 730: 704: 701: 695: 694: 691: 688: 687:Plasma protein 685: 682: 679: 676: 670: 669: 666: 663: 662:Plasma protein 660: 652: 649: 648:Hageman factor 646: 640: 639: 636: 633: 632:Plasma protein 630: 625: 622: 620: 619: 616: 612: 610: 604: 603: 600: 597: 594: 591: 588:prothrombinase 584: 582: 581: 578: 574: 572: 565: 564: 561: 558: 557:Plasma protein 555: 550: 543: 541: 540: 537: 534: 530: 528: 521: 520: 517: 514: 511: 506: 499: 497: 496: 493: 490: 486: 484: 478: 477: 474: 471: 470:Plasma protein 468: 462: 459: 457: 456: 453: 450: 446: 444: 437: 436: 434: 431: 428: 425: 423: 422: 419: 408: 406: 402: 401: 398: 395: 394:Plasma protein 392: 387: 384:prothrombinase 380: 378: 377: 374: 371: 367: 365: 359: 358: 355: 352: 349: 347: 344: 342: 341: 338: 335: 331: 329: 325: 324: 321: 318: 315: 313: 310: 308: 307: 304: 298: 296: 292: 291: 288: 285: 284:Plasma protein 282: 280: 279: 273: 267: 265: 255: 250: 246: 245: 242: 239: 237:Plasma protein 234: 232: 231: 226: 220: 218: 215: 210: 206: 205: 202: 199: 196: 193: 190: 187: 174: 171: 60: 59: 56: 52: 51: 41: 33: 32: 15: 13: 10: 9: 6: 4: 3: 2: 6166: 6155: 6152: 6150: 6147: 6146: 6144: 6129: 6126: 6124: 6121: 6119: 6116: 6114: 6111: 6110: 6107: 6103: 6100: 6093: 6088: 6086: 6081: 6079: 6074: 6073: 6070: 6054: 6051: 6049: 6042: 6041: 6039: 6037: 6033: 6027: 6024: 6022: 6019: 6017: 6014: 6013: 6011: 6009: 6005: 5999: 5996: 5994: 5991: 5989: 5986: 5985: 5983: 5981: 5977: 5971: 5968: 5966: 5963: 5962: 5960: 5958: 5954: 5951: 5949: 5945: 5939: 5936: 5934: 5927: 5925: 5918: 5916: 5913: 5911: 5908: 5906: 5903: 5901: 5898: 5896: 5893: 5891: 5888: 5887: 5885: 5883: 5879: 5873: 5870: 5868: 5865: 5863: 5860: 5858: 5855: 5853: 5850: 5848: 5845: 5844: 5842: 5840: 5836: 5826: 5823: 5821: 5818: 5815: 5811: 5807: 5804: 5802: 5799: 5797: 5794: 5792: 5789: 5787: 5784: 5783: 5781: 5779: 5775: 5769: 5766: 5764: 5761: 5760: 5758: 5756: 5750: 5744: 5741: 5739: 5736: 5734: 5731: 5729: 5726: 5724: 5721: 5719: 5718:Prekallikrein 5716: 5714: 5711: 5709: 5706: 5705: 5703: 5701: 5695: 5689: 5686: 5683: 5680: 5678: 5674: 5671: 5668: 5665: 5663: 5660: 5658: 5654: 5651: 5649: 5645: 5643: 5640: 5639: 5637: 5635: 5629: 5626: 5624: 5620: 5616: 5609: 5604: 5602: 5597: 5595: 5590: 5589: 5586: 5579: 5574: 5570: 5569: 5565: 5559: 5555: 5551: 5547: 5543: 5539: 5534: 5530: 5526: 5522: 5518: 5514: 5510: 5506: 5502: 5498: 5493: 5492: 5488: 5479: 5475: 5470: 5465: 5461: 5457: 5453: 5449: 5445: 5441: 5437: 5430: 5427: 5422: 5418: 5413: 5408: 5404: 5400: 5396: 5389: 5386: 5381: 5377: 5373: 5369: 5364: 5359: 5355: 5351: 5347: 5343: 5339: 5332: 5329: 5324: 5320: 5315: 5310: 5306: 5302: 5298: 5291: 5288: 5283: 5279: 5275: 5271: 5267: 5263: 5259: 5255: 5251: 5247: 5240: 5237: 5232: 5228: 5224: 5220: 5216: 5212: 5208: 5204: 5200: 5196: 5189: 5186: 5181: 5177: 5173: 5169: 5165: 5161: 5157: 5153: 5146: 5144: 5142: 5140: 5138: 5136: 5132: 5127: 5123: 5119: 5115: 5111: 5107: 5100: 5097: 5092: 5088: 5083: 5078: 5074: 5070: 5066: 5059: 5056: 5051: 5047: 5043: 5039: 5035: 5031: 5024: 5021: 5016: 5012: 5005: 5002: 4996: 4993: 4988: 4984: 4980: 4976: 4972: 4968: 4961: 4958: 4953: 4949: 4944: 4939: 4935: 4931: 4927: 4920: 4917: 4912: 4908: 4904: 4900: 4896: 4892: 4888: 4884: 4880: 4876: 4872: 4865: 4862: 4855: 4852: 4847: 4843: 4838: 4833: 4829: 4825: 4821: 4817: 4813: 4806: 4803: 4796: 4793: 4786: 4783: 4770: 4766: 4762: 4756: 4753: 4740: 4736: 4732: 4728: 4722: 4718: 4714: 4713: 4705: 4702: 4696: 4693: 4681: 4677: 4671: 4668: 4661: 4658: 4653: 4649: 4645: 4639: 4635: 4631: 4627: 4620: 4618: 4614: 4609: 4603: 4599: 4594: 4593: 4584: 4581: 4575: 4572: 4565: 4563: 4559: 4554: 4550: 4545: 4540: 4535: 4530: 4526: 4522: 4518: 4511: 4508: 4503: 4499: 4494: 4489: 4484: 4479: 4475: 4471: 4470:Critical Care 4467: 4460: 4457: 4452: 4448: 4443: 4438: 4434: 4430: 4426: 4422: 4418: 4414: 4410: 4406: 4402: 4395: 4392: 4387: 4383: 4378: 4373: 4369: 4365: 4360: 4355: 4351: 4347: 4343: 4336: 4333: 4328: 4324: 4319: 4314: 4310: 4306: 4301: 4296: 4292: 4288: 4284: 4277: 4274: 4267: 4264: 4257: 4254: 4250: 4246: 4243: 4238: 4235: 4230: 4224: 4220: 4213: 4211: 4207: 4194: 4190: 4186: 4182: 4178: 4174: 4170: 4166: 4162: 4158: 4151: 4148: 4142: 4139: 4132: 4129: 4123: 4120: 4115: 4111: 4106: 4101: 4097: 4093: 4090:(6): 102160. 4089: 4085: 4081: 4074: 4071: 4066: 4062: 4057: 4052: 4048: 4044: 4040: 4033: 4031: 4027: 4014: 4010: 4006: 4002: 3996: 3992: 3991: 3983: 3980: 3967: 3963: 3959: 3953: 3950: 3945: 3939: 3935: 3928: 3926: 3924: 3922: 3920: 3918: 3916: 3912: 3899: 3895: 3891: 3887: 3881: 3877: 3876: 3868: 3865: 3860: 3854: 3849: 3848: 3839: 3836: 3831: 3827: 3822: 3817: 3813: 3809: 3804: 3799: 3795: 3791: 3787: 3780: 3777: 3772: 3768: 3763: 3758: 3754: 3750: 3746: 3742: 3738: 3731: 3728: 3716: 3712: 3708: 3704: 3700: 3693: 3690: 3685: 3681: 3676: 3671: 3667: 3663: 3659: 3653: 3649: 3645: 3641: 3634: 3632: 3628: 3615: 3611: 3607: 3601: 3598: 3593: 3587: 3583: 3582: 3577: 3570: 3567: 3562: 3558: 3554: 3550: 3546: 3542: 3537: 3532: 3528: 3524: 3520: 3513: 3510: 3505: 3501: 3496: 3491: 3487: 3483: 3478: 3473: 3469: 3465: 3461: 3457: 3453: 3446: 3443: 3438: 3434: 3430: 3426: 3422: 3418: 3414: 3407: 3404: 3399: 3395: 3391: 3387: 3383: 3378: 3373: 3369: 3365: 3361: 3354: 3351: 3338: 3334: 3333: 3328: 3322: 3319: 3306: 3302: 3298: 3294: 3290: 3286: 3282: 3278: 3274: 3270: 3263: 3260: 3255: 3251: 3247: 3243: 3239: 3235: 3231: 3227: 3223: 3216: 3213: 3200: 3196: 3192: 3186: 3183: 3170: 3166: 3162: 3156: 3153: 3148: 3144: 3139: 3134: 3130: 3126: 3121: 3116: 3112: 3108: 3104: 3097: 3094: 3081: 3077: 3076:ScienceDirect 3073: 3067: 3065: 3061: 3048: 3044: 3040: 3034: 3031: 3026: 3020: 3016: 3011: 3009: 3005: 3000: 2993: 2990: 2985: 2979: 2974: 2973: 2964: 2961: 2948: 2944: 2940: 2936: 2930: 2926: 2925: 2917: 2914: 2902: 2898: 2892: 2890: 2886: 2873: 2869: 2865: 2861: 2855: 2851: 2850: 2842: 2839: 2834: 2830: 2825: 2820: 2816: 2812: 2808: 2804: 2800: 2793: 2790: 2783: 2779: 2776: 2774: 2771: 2769: 2766: 2765: 2761: 2750: 2745: 2743: 2741: 2737: 2729:Other species 2728: 2726: 2723: 2721: 2717: 2716:prekallikrein 2712: 2709:The usage of 2704: 2702: 2699: 2695: 2693: 2689: 2685: 2681: 2677: 2672: 2670: 2666: 2662: 2658: 2656: 2652: 2647: 2643: 2638: 2634: 2629: 2623: 2621: 2619: 2615: 2611: 2607: 2603: 2599: 2598:Paul Morawitz 2595: 2594:tissue factor 2590: 2588: 2584: 2580: 2576: 2572: 2568: 2564: 2561:(1799–1863). 2560: 2556: 2552: 2548: 2544: 2536: 2531: 2529: 2527: 2523: 2519: 2515: 2511: 2507: 2503: 2499: 2495: 2491: 2486: 2482: 2479:(and related 2478: 2474: 2470: 2466: 2462: 2458: 2454: 2450: 2446: 2442: 2436: 2435:Anticoagulant 2432: 2424: 2419: 2415: 2411: 2407: 2403: 2401: 2397: 2393: 2389: 2385: 2383: 2379: 2375: 2371: 2367: 2362: 2360: 2356: 2352: 2350: 2346: 2342: 2338: 2334: 2327: 2322: 2318:Procoagulants 2317: 2312: 2310: 2308: 2304: 2300: 2296: 2292: 2288: 2284: 2280: 2276: 2272: 2270: 2269:liver failure 2265: 2263: 2259: 2257: 2253: 2249: 2245: 2237: 2235: 2233: 2229: 2225: 2221: 2217: 2213: 2209: 2205: 2201: 2197: 2192: 2190: 2186: 2182: 2178: 2174: 2170: 2166: 2162: 2158: 2150: 2145: 2141: 2136: 2132: 2126: 2124: 2122: 2117: 2115: 2110: 2108: 2104: 2099: 2097: 2093: 2089: 2085: 2084:tissue factor 2080: 2078: 2074: 2066: 2062: 2058: 2054: 2050: 2046: 2042: 2038: 2034: 2033:bleeding time 2030: 2026: 2023: 2019: 2015: 2011: 2007: 2003: 1999: 1995: 1991: 1990: 1989: 1983: 1981: 1979: 1967: 1960: 1958: 1956: 1952: 1945: 1943: 1941: 1934: 1932: 1930: 1926: 1922: 1918: 1914: 1910: 1906: 1899: 1897: 1895: 1891: 1890:thrombophilia 1887: 1883: 1879: 1875: 1868: 1866: 1859: 1852: 1850: 1848: 1847:liver failure 1844: 1843:malabsorption 1840: 1836: 1835:phenprocoumon 1832: 1831:acenocoumarol 1828: 1824: 1820: 1819: 1814: 1810: 1806: 1802: 1801:glutamic acid 1798: 1794: 1790: 1783: 1781: 1778: 1777:microvesicles 1773: 1769: 1765: 1764:phospholipids 1761: 1754: 1752: 1746: 1744: 1742: 1738: 1734: 1730: 1724: 1722: 1721:streptokinase 1718: 1714: 1710: 1706: 1702: 1698: 1694: 1693:antimicrobial 1690: 1686: 1682: 1678: 1677:immune system 1670: 1668: 1666: 1662: 1658: 1654: 1653: 1646: 1638: 1636: 1634: 1629: 1627: 1626: 1617: 1615: 1613: 1608: 1606: 1602: 1598: 1594: 1589: 1585: 1578: 1576: 1573: 1572:prekallikrein 1568: 1564: 1560: 1559:Prekallikrein 1556: 1552: 1551:prekallikrein 1548: 1544: 1540: 1532: 1527: 1523: 1520: 1517: 1513: 1509: 1506: 1502: 1499: 1496: 1493: 1489: 1488: 1487: 1485: 1481: 1480:tissue factor 1473: 1471: 1469: 1465: 1464:tissue factor 1461: 1457: 1453: 1449: 1444: 1442: 1438: 1434: 1430: 1426: 1422: 1421:tissue factor 1418: 1414: 1410: 1409: 1398: 1390: 1386: 1381: 1379: 1377: 1373: 1369: 1365: 1361: 1349: 1342: 1338: 1326: 1322:thromboxane A 1319: 1315: 1311: 1307: 1303: 1298: 1295: 1291: 1287: 1283: 1279: 1271: 1269: 1264: 1256: 1254: 1252: 1248: 1244: 1239: 1235: 1227: 1223: 1222:wound healing 1219: 1215: 1211: 1208: 1205: 1202: 1197: 1194: 1190: 1186: 1182: 1178: 1174: 1170: 1169: 1167: 1166:platelet plug 1163: 1160: 1156: 1152: 1149: 1148: 1147: 1144: 1142: 1132: 1125: 1117: 1114: 1112: 1108: 1104: 1102: 1100: 1097: 1096: 1092: 1089: 1086: 1084: 1081: 1080: 1076: 1073: 1070: 1068: 1065: 1064: 1061: 1058: 1055: 1053: 1051: 1048: 1047: 1041: 1040:Thrombophilia 1038: 1036: 1032: 1031: 1029: 1026: 1023: 1021: 1018: 1017: 1014: 1011: 1009: 1007: 1000: 999: 995: 992: 990: 988: 981: 980: 976: 973: 971: 969: 966: 965: 962: 959: 956: 954: 951: 950: 947: 944: 941: 939: 937: 934: 933: 930: 927: 924: 922: 920: 917: 916: 913: 910: 907: 905: 903: 900: 899: 895: 892: 888: 886: 884: 881: 880: 877: 874: 871: 869: 866: 863: 862: 858: 855: 852: 850: 848: 845: 844: 841: 838: 835: 829: 826: 825: 823: 821: 818: 817: 814: 811: 809: 807: 804: 803: 799: 796: 793: 791: 790:Prekallikrein 788: 787: 784: 779: 775: 772: 770: 767: 764: 762: 760: 757: 756: 752: 747: 742: 739: 736: 734: 731: 729: 725: 721: 717: 716:glutamic acid 713: 709: 705: 702: 700: 697: 696: 692: 689: 686: 683: 680: 677: 675: 672: 671: 667: 664: 661: 657: 653: 650: 647: 645: 642: 641: 637: 634: 631: 629: 626: 623: 617: 614: 613: 611: 609: 606: 605: 601: 598: 595: 592: 589: 585: 580:Stuart factor 579: 576: 575: 573: 570: 567: 566: 562: 559: 556: 554: 551: 548: 544: 538: 535: 532: 531: 529: 526: 523: 522: 518: 515: 512: 510: 507: 504: 500: 494: 491: 488: 487: 485: 483: 480: 479: 475: 472: 469: 467: 463: 460: 455:Stable factor 454: 451: 448: 447: 445: 442: 439: 438: 435: 432: 429: 426: 420: 413: 410: 409: 407: 404: 403: 399: 396: 393: 391: 388: 385: 381: 375: 373:labile factor 372: 369: 368: 366: 364: 361: 360: 356: 353: 350: 348: 345: 339: 336: 333: 332: 330: 327: 326: 322: 319: 316: 314: 311: 305: 303: 302:Tissue factor 300: 299: 297: 294: 293: 289: 286: 283: 277: 274: 272: 271:Thrombophilia 269: 268: 266: 264: 260: 256: 254: 251: 248: 247: 243: 240: 238: 235: 230: 227: 225: 222: 221: 219: 216: 214: 211: 208: 207: 203: 200: 197: 194: 191: 188: 185: 184: 178: 172: 170: 168: 164: 160: 156: 155:proteinaceous 152: 148: 143: 141: 140:platelet plug 137: 133: 129: 125: 121: 117: 114:that lines a 113: 108: 106: 102: 98: 94: 90: 86: 82: 78: 74: 70: 66: 57: 53: 49: 45: 39: 34: 29: 26: 22: 6118:Fibrinolysis 6112: 6098: 6053:D-Dimer (DD) 6036:Fibrinolysis 5924:-Antiplasmin 5646: 5541: 5537: 5504: 5500: 5446:(4): 110–9. 5443: 5439: 5429: 5402: 5398: 5388: 5345: 5341: 5331: 5304: 5300: 5290: 5249: 5245: 5239: 5198: 5194: 5188: 5155: 5151: 5109: 5105: 5099: 5072: 5068: 5058: 5033: 5029: 5023: 5014: 5010: 5004: 4995: 4970: 4966: 4960: 4933: 4929: 4919: 4878: 4874: 4864: 4854: 4819: 4815: 4805: 4795: 4790:PMC11007487. 4785: 4773:. Retrieved 4764: 4755: 4743:. Retrieved 4711: 4704: 4695: 4683:. Retrieved 4679: 4670: 4660: 4625: 4591: 4583: 4574: 4569:PMC10816375. 4524: 4520: 4510: 4473: 4469: 4459: 4411:(1): 11324. 4408: 4404: 4394: 4349: 4345: 4335: 4290: 4286: 4276: 4266: 4256: 4237: 4218: 4197:. Retrieved 4164: 4160: 4150: 4141: 4131: 4122: 4087: 4083: 4073: 4046: 4042: 4017:. Retrieved 3989: 3982: 3970:. Retrieved 3961: 3952: 3933: 3902:. Retrieved 3874: 3867: 3846: 3838: 3793: 3789: 3779: 3744: 3740: 3730: 3719:, retrieved 3702: 3692: 3639: 3618:. Retrieved 3609: 3600: 3580: 3569: 3526: 3522: 3512: 3459: 3455: 3445: 3420: 3416: 3406: 3367: 3363: 3353: 3341:. Retrieved 3337:the original 3331: 3321: 3309:. Retrieved 3276: 3272: 3262: 3232:(2): 73–86. 3229: 3225: 3215: 3203:. Retrieved 3194: 3185: 3173:. Retrieved 3164: 3155: 3110: 3106: 3096: 3084:. Retrieved 3080:the original 3075: 3053:11 September 3051:. Retrieved 3042: 3033: 3014: 2996: 2992: 2971: 2963: 2951:. Retrieved 2923: 2916: 2904:. Retrieved 2900: 2876:. Retrieved 2848: 2841: 2806: 2802: 2792: 2732: 2724: 2708: 2705:Nomenclature 2700: 2696: 2691: 2676:hemophilia B 2673: 2668: 2665:hemophilia A 2659: 2655:proconvertin 2654: 2650: 2648: 2633:proaccelerin 2632: 2630: 2627: 2617: 2613: 2612:(IV), forms 2605: 2601: 2591: 2540: 2449:dipyridamole 2438: 2395: 2386: 2363: 2355:Desmopressin 2353: 2339:, and other 2330: 2321: 2313:Pharmacology 2273: 2266: 2260: 2256:hemophilia C 2252:hemophilia B 2248:hemophilia A 2241: 2193: 2154: 2130: 2118: 2114:hemophilia A 2111: 2106: 2100: 2081: 2070: 2009: 1987: 1966:Prostacyclin 1964: 1961:Prostacyclin 1949: 1938: 1905:Antithrombin 1903: 1900:Antithrombin 1872: 1864: 1825:and related 1816: 1795:that adds a 1787: 1758: 1750: 1725: 1713:inflammation 1674: 1652:fibrinolysis 1650: 1648: 1645:Fibrinolysis 1639:Fibrinolysis 1630: 1623: 1621: 1609: 1590: 1586: 1582: 1536: 1518:to thrombin. 1477: 1467: 1463: 1445: 1440: 1433:glycoprotein 1420: 1416: 1412: 1406: 1404: 1385: 1299: 1275: 1266: 1231: 1218:factor XIIIa 1155:tunica media 1145: 1138: 987:-Antiplasmin 865:Antithrombin 710:that adds a 628:Hemophilia C 553:Hemophilia B 509:Hemophilia A 449:Proconvertin 411: 370:Proaccelerin 337:Calcium ions 176: 144: 136:listed below 131: 116:blood vessel 109: 83:, forming a 68: 64: 63: 43: 25: 6113:Coagulation 6099:Coagulation 5890:Plasminogen 5825:Factor XIII 5743:Factor VIII 5578:Coagulation 5544:(1): 1–11. 5112:: 307–422. 4973:: 413–538. 4712:Haematology 4626:Haemostasis 4352:: 489–495. 4136:PMC9035508. 3934:Haematology 3875:Haematology 3273:Haemostasis 3205:8 September 3175:8 September 3086:9 September 3043:MedlinePlus 2661:Factor VIII 2640: [ 2606:prothrombin 2575:prothrombin 2518:rivaroxaban 2502:bivalirudin 2473:angioplasty 2457:clopidogrel 2453:ticlopidine 2410:Rivaroxaban 2331:The use of 2244:hemophilias 2179:(deficient 2171:(deficient 2053:prothrombin 2037:mixing test 1929:proteinuria 1697:beta-lysine 1516:prothrombin 1251:plasminogen 1210:Fibrin clot 1168:formation: 1159:endothelium 1024:t-PA or TPA 968:Plasminogen 847:Fibronectin 782:bone marrow 674:Factor XIII 482:Factor VIII 464:Congenital 376:Ac-globulin 253:Prothrombin 204:Pathway(s) 186:Number/Name 112:endothelium 65:Coagulation 31:Coagulation 6143:Categories 6102:physiology 5768:Factor VII 5723:Kallikrein 5713:Bradykinin 5017:: 739–746. 4745:8 February 4735:1058077604 4527:(2): 362. 4476:(1): 212. 4199:8 February 4019:8 February 3904:8 February 3894:1023165019 3721:15 October 3703:StatPearls 3620:15 October 3343:15 October 3311:15 October 3113:: e05826. 2953:8 February 2878:8 February 2784:References 2637:Paul Owren 2551:fibrinogen 2514:dabigatran 2506:dabigatran 2498:argatroban 2461:ticagrelor 2366:hemophilia 2275:Thrombosis 2163:(abnormal 2006:fibrinogen 1853:Regulators 1593:fibrinogen 1563:kallikrein 1372:fibrinogen 1368:fibrinogen 1245:, such as 1175:, such as 1141:hemostasis 1126:Physiology 806:Kallikrein 778:endothelia 753:Extrinsic 644:Factor XII 638:Intrinsic 563:Intrinsic 519:Intrinsic 476:Extrinsic 441:Factor VII 412:Unassigned 323:Extrinsic 295:Factor III 249:Factor II* 213:Fibrinogen 189:Synonym(s) 167:thrombosis 159:hemorrhage 93:activation 89:hemostasis 85:blood clot 58:Beneficial 6044:Plasmin-α 5905:Urokinase 5738:Factor IX 5733:Factor XI 4895:1538-7836 4800:38702892. 4665:32049377. 4433:2045-2322 4368:1176-6344 4309:0019-5049 4271:37890148. 4261:26485450. 4009:898998816 3812:1471-2261 3753:0730-2347 3666:0306-0225 3545:0735-1097 3486:0027-8424 3386:0021-9258 3293:0301-0147 3246:0957-5235 3129:2050-084X 3008:CC BY 4.0 2943:779160978 2868:909782638 2849:Platelets 2740:hemocytes 2589:in 1882. 2583:Platelets 2567:enzymatic 2494:lepirudin 2481:coumarins 2465:prasugrel 2400:aprotinin 2333:adsorbent 1886:protein S 1874:Protein C 1839:dicumarol 1827:coumarins 1813:Protein Z 1809:Protein C 1805:Protein S 1799:group to 1789:Vitamin K 1784:Vitamin K 1747:Cofactors 1717:coagulase 1633:platelets 1597:protein C 1362:membrane 1306:serotonin 1157:layer of 1050:Urokinase 1033:Familial 936:Protein Z 919:Protein S 902:Protein C 728:Protein Z 724:Protein C 720:Protein S 714:group to 699:Vitamin K 608:Factor XI 525:Factor IX 405:Factor VI 328:Factor IV 263:protein C 259:platelets 147:conserved 101:platelets 5791:Factor V 5786:Factor X 5558:17258114 5529:18681597 5521:11434702 5478:24019589 5421:37890148 5380:24537601 5372:15170505 5363:11138774 5323:14008442 5282:34111840 5274:14173416 5223:14167839 5180:22694905 5172:12780784 5126:84003009 5091:16643426 5050:14585945 4987:37273997 4952:22345595 4911:30749769 4903:12871401 4846:31778223 4769:Archived 4739:Archived 4685:28 April 4652:23546714 4553:38256496 4544:10816375 4502:38956732 4493:11218309 4451:31383913 4386:33273818 4327:25535411 4245:Archived 4193:Archived 4189:19974377 4181:14760207 4114:37727847 4105:10506138 4065:26707513 4013:Archived 3966:Archived 3898:Archived 3830:26481314 3715:archived 3711:31424847 3684:28101869 3614:Archived 3561:23789418 3437:19355974 3398:Archived 3305:Archived 3199:Archived 3169:Archived 3147:25807083 3047:Archived 3010:license. 2947:Archived 2906:27 April 2872:Archived 2833:16322780 2746:See also 2614:thrombin 2571:thrombin 2547:thrombus 2526:edoxaban 2522:apixaban 2477:warfarin 2443:include 2396:de facto 2337:zeolites 2295:necrosis 2291:ischemia 2287:thrombus 2283:embolism 2096:warfarin 2014:platelet 1992:Common: 1925:heparins 1829:such as 1823:warfarin 1797:carboxyl 1768:platelet 1703:of many 1549:(HMWK), 1543:collagen 1484:thrombin 1460:zymogens 1431:and its 1360:integrin 1214:thrombin 1193:collagen 1107:factor X 712:carboxyl 658:type III 569:Factor X 363:Factor V 209:Factor I 192:Function 163:bruising 97:adhesion 69:clotting 48:thrombin 5895:Plasmin 5469:3756735 5448:Bibcode 5314:1848865 5254:Bibcode 5246:Science 5231:4214940 5203:Bibcode 4837:6993082 4775:12 July 4442:6683118 4413:Bibcode 4377:7705281 4318:4260295 3821:4617895 3796:: 130. 3771:7647603 3675:5536120 3553:3537069 3504:6320190 3464:Bibcode 3394:2440865 3301:2083865 3254:9518049 3138:4373459 2824:1297262 2610:calcium 2532:History 2485:heparin 2445:aspirin 2305:(e.g., 2279:embolus 2175:), and 2045:D-dimer 2027:Other: 2018:PFA-100 1951:Plasmin 1946:Plasmin 1760:Calcium 1657:plasmin 1625:in vivo 1507:(TFPI). 1492:stromal 1450:called 1448:enzymes 1425:zymogen 1312:(PAF), 1135:(blue). 1111:cancers 746:E. coli 596:Protein 505:complex 386:complex 340:Ca ions 334:Calcium 151:mammals 44:in vivo 5682:GPIIIa 5556: 5527: 5519: 5476: 5466: 5419: 5378: 5370: 5360: 5321: 5311: 5280: 5272: 5229: 5221: 5195:Nature 5178: 5170: 5124: 5089: 5048: 4985: 4950: 4909: 4901: 4893: 4844: 4834: 4733: 4723: 4719:–166. 4650: 4640: 4604: 4551: 4541: 4500: 4490: 4449: 4439: 4431: 4384: 4374: 4366: 4325: 4315: 4307: 4225: 4187: 4179: 4112: 4102: 4063: 4007: 3997: 3972:20 May 3940: 3892: 3882: 3855: 3828: 3818: 3810: 3769: 3762:325239 3759: 3751: 3709: 3682: 3672: 3664: 3654: 3588: 3559: 3551: 3543: 3502: 3495:344699 3492: 3484: 3435: 3392: 3384: 3299: 3291: 3252: 3244: 3145: 3135: 3127: 3021: 2980: 2941: 2931: 2866: 2856: 2831: 2821: 2678:named 2618:fibrin 2579:Arthus 2524:, and 2483:) and 2067:(ELT). 1913:serpin 1837:, and 1772:tenase 1612:tenase 1567:tenase 1553:, and 1526:tenase 1408:fibrin 1354:). 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