There are two interconnected mechanisms underlying the plasma coagulation cascade figure 2 37. Pdf intrinsic pathway of coagulation and thrombosis. It is known that the platelet expresses membrane sites for assembly of factors ixaviii and promotes efficient factor x activation. Subsets of these factors can be activated by two distinct pathways, the extrinsic, or tissue damage pathway blue arrows, and the intrinsic, or contact pathway green arrows. Difference between intrinsic and extrinsic pathways in. Coagulation blood coagulation pathways in vivo showing the central role played by thrombin healthbeneficial coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. Abstractformation of a fibrin clot is mediated by a group of tightly regulated plasma proteases and cofactors. This phenomenon of formation of clot is called as coagulation or clotting of blood. We now show that human blood monocytes, but not lymphocytes or polymorphonuclear leukocytes, also express appropriate sites for factors. Pdf intrinsic pathway of coagulation and arterial thrombosis. Tracy chuong university of california, santa barbara.
Explain how the extrinsic and intrinsic coagulation pathways lead to the common pathway, and the coagulation factors involved in each discuss disorders affecting hemostasis platelets are key players in hemostasis, the process by which the body seals a ruptured blood vessel and prevents further loss of blood. Vessel wall injuryinduced exposure of extravascular tissue factor to circulating coagulation factor viia fviia activates the extrinsic coagulation cascade, which, through subsequent activation of coagulation fix, fx, and fii prothrombin, ultimately produces a fibrin and platelet crosslinked clot at the site of. Appropriate activation of coagulation in response to vascular injury is required for effective hemostasis that facilitates the cessation of bleeding. The intrinsic pathway also called the contact activation pathway is much less significant to hemostasis under normal physiological conditions than is the extrinsic pathway. For a long time it was believed that coagulation of blood had to do with cold temperature. The study of blood coagulation can be traced back to about 400bc and the father of medicine, hippocrates 9. The big picture trauma injury accounts for 30% of all life years. The influence of intrinsic coagulation pathway on blood platelets activation by oxidized cellulose. Jul 05, 2017 intrinsic pathway enters into a common pathway of blood coagulation after activating prothrombin activator. The coagulation factors circulate in the form of inactive precursors. P3620the extrinsic and intrinsic pathways of coagulation are. The coagulation time represents the time from the collection of blood until its complete coagulation.
This reaction is facilitated by the presence of highmolecularweight kininogen hmwk and the conversion of prekallikrein. The classical concept of an intrinsic and extrinsic pathway of coagulation can make one think that both systems act independently from each other. The intrinsic pathway of coagulation wiley online library. When blood is shed, it looses its fluidity within few minutes and sets into a semisolid jelly called clot. The extrinsic pathway is initiated upon vascular injury which leads to exposure of tissue factor, tf also identified as factor iii, a subendothelial cell. Inhibition of the intrinsic coagulation pathway factor xi by. Activation of the intrinsic pathway of coagulation contributes to the pathogenesis of arterial and venous thrombosis. Clotting in tube from traumatic venipuncture or inadequate mixing hemodilution of sample 2. It is known that blood coagulation is activated in two pathways. Therefore the intrinsic pathway is not likely to be of impor tance to normal blood coagulation. Extrinsic pathway factors factor vii intrinsic pathway factors factors xii, xi, six, viii common pathway factors factors x, v, ii, fibrinogen s memorizing which factors belong to the extrinsic, intrinsic and common pathways respectively will make evaluating the causes of abnormal coagulation. It has relevance when it is prolonged, but one cannot establish where the deficiency is on the intrinsic, extrinsic or common pathway. Old model normal coagulation cascade turecek pl et al. From the division of hematology and oncology, department of medicine, unc blood research center, university of north carolina at chapel.
This assay is routinely used to evaluate defects in the intrinsic pathway of coagulation, such as hemophilia a and b. During the early events of coagulation of human blood by the intrinsic pathway, factor xii is activated to a form which can activate factor xi, and is proteolytically fragmented to smaller species. Intrinsic pathway of blood coagulation contributes to. Extrinsic pathway factors factor vii intrinsic pathway factors factors xii, xi, six, viii common pathway factors factors x, v, ii, fibrinogen s memorizing which factors belong to the extrinsic, intrinsic and common pathways respectively will make evaluating the causes of abnormal coagulation tests easier. Key difference intrinsic vs extrinsic pathways in blood clotting blood clotting is an important process to stop bleeding. The coagulation cascade of secondary hemostasis has two initial pathways which lead to fibrin formation. Moreover, it can give the impression that there is not a strict qualitycontrol system that governs both pathways. The clotting cascade occurs through two separate pathways that interact, the intrinsic and the extrinsic pathway.
The intricate pathway allows for rapid healing and prevention of spontaneous bleeding. The intrinsic pathway is triggered by the contact of factor xii f xii with the subendothelial space and its subsequent activation. Initiation of fibrin formation occurs at a site of blood vessel injury when plasma fviia binds to tissue factor tf, a membrane protein constitutively. If there is no protein c, the normal inhibition mechanism of the intrinsic pathway is turned off. Activation of the intrinsic pathway of blood coagulation proceeds in a series of steps, initiated when factor xii is activated by exposure to a foreign surface. Procoagulant stimulus processing by the intrinsic pathway of.
Hippocrates and aristotle both described in detail various internal and superficial bleeding tendencies. Procoagulant stimulus processing by the intrinsic pathway of blood plasma coagulation a contribution from the hematology at biomaterial interfaces research group the pennsylvania state university by rui zhuo, rachel miller, karen m. This means there is an increased tendency to clot via the intrinsic pathway. Role of the extrinsic pathway of blood coagulation in. Kumbakonam rajagopal blood is a complex mixture of formed cellular elements, proteins, and ions dissolved in a solution. These are the contact activation pathway also known as the intrinsic pathway, and the tissue factor pathway also known as the extrinsic pathway, which both lead to the same fundamental reactions that produce fibrin. View the article pdf and any associated supplements and figures for a period of 48 hours. Exposure of specific coagulation factors to subendothelial collagen is the inciting event for the initiation of this pathway 4 figure 1. The extrinsic pathway consists of the transmembrane receptor tissue factor tf and plasma factor viiviia fviifviia, and the intrinsic pathway consists of. Bandodkar college of science, thane paper ii haematology. Extrinsic and intrinsic coagulation pathway, fibrinogen.
Extrinsic pathway factors factor vii intrinsic pathway factors factors xii, xi, ix, viii common pathway factors factors x, v, ii, fibrinogen memorizing which factors belong to the extrinsic, intrinsic and common pathways respectively will make evaluating the causes of abnormal coagulation tests easier. Extrinsic and intrinsic coagulation pathway, fibrinogen serum. Physiology, coagulation pathways statpearls ncbi bookshelf. Intrinsic pathway is a type of blood clotting pathway which is activated by a trauma in blood or when blood is exposed to a subendothelial collagen. A mathematical model has been developed to simulate the generation of thrombin through intrinsic and extrinsic pathways. Two paths, intrinsic and extrinsic, originate separately. Nov 25, 2010 precise regulation of blood coagulation is critical for normal hemostasis. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. Triggered by the exposure of tissue factor in the damaged blood vessel wall to the circulating factor vii. It is known that the platelet ex presses membrane sites for assembly of factors ixa vi11 and promotes efficient factor x activation. It is a complicated process which occurs via series of activation processes collectively called coagulation cascade. Difference between intrinsic and extrins ic pathways in blood clotting. Blood clotting mechanisms blood clotting refers to the process of creating a clot to stop bleeding.
Inmodelsofarterialinjury,fxiiorfxinullmiceareprotected from formation of platelet rich occlusive thrombi to a degree. Extrinsic pathway factors factor vii intrinsic pathway factors factors xii, xi, ix, viii common pathway factors factors x, v, ii, fibrinogen memorizing which factors belong to the extrinsic, intrinsic and common pathways respectively will make evaluating the causes of abnormal coagulation. At sites of vessel injury, bleeding is minimized by the formation of a hemostatic plug consisting of platelets and fibrin. Functional difference between intrinsic and extrinsic. The extrinsic pathway consists of the transmembrane receptor tissue factor tf and plasma factor viiviia fviifviia, and the intrinsic pathway. Difference between intrinsic and extrinsic pathways in blood. The pt is the in vitro clotting time measured after. This pathway is quicker than the intrinsic pathway. Oct 28, 2020 the intrinsic pathway is the contact activation pathway. Jun 15, 2002 a major role in determining thrombogenicity of human atherosclerotic lesions has been ascribed to the extrinsic, tissue factor tfdependent pathway of blood coagulation. The extrinsic pathway is initiated by the tissue factor tf, which forms a complex with factor vii f vii and activates it. Intrinsic pathway of coagulation and thrombosis arteriosclerosis. Little effect on blood coagulation, but a pronounce decrease in platelet count has been reported upon the addition of the oxidized cellulose to the whole blood.
Bleeding and blood clotting bleeding and blood clotting the extrinsic pathway of blood coagulation. Extrinsic pathway the extrinsic pathway is activated by external trauma that causes blood to escape from the vascular system. Procoagulant stimulus processing by the intrinsic pathway. The protein on the surface of cells that is responsible for the initiation of blood clotting is known as tissue factor, or tissue thromboplastin. The intrinsic cascade which has less in vivo significance in normal physiological circumstances than the extrinsic cascade is initiated when contact is made between blood and exposed negatively charged surfaces. It is a global test that explores the overall coagulation. Blood coagulation factor an overview sciencedirect topics. We now show that human blood monocytes, but not lym.
However, abnormal physiology such as hyperlipidemic states or bacterial infiltration can lead to activation of thrombosis via the intrinsic clotting cascade. Tracy chuong university of california, santa barbara department of chemistry and biochemistry. In contrast, ptt test was normal showing normal function of the extrinsic pathway. However, recent work with mice lacking fxii or fxi suggest that these proteases make important contributionstoformationofpathologicintravascularthrombi. When prothrombin activator is activated, it facilitates the conversion of prothrombin into thrombin. Molecular biology and biochemistry of the coagulation factors and pathways of blood coagulation. This pathway is slower than the extrinsic pathway, but more important.
Activation of coagulation factor x via the intrinsic pathway requires the assembly of factors ixa and viii on lipid membranes. The influence of intrinsic coagulation pathway on blood. A model for blood coagulation and lysis utilizing the intrinsic and extrinsic pathways. Recent studies have identified endogenous activators of contact system, such as polyphospahte, collagen, misfolded protein aggregates, lipopolysaccharides lps, glycosamino. Mathematical modeling of blood coagulation cascade. Inhibition of the intrinsic coagulation pathway factor xi. As described above, the biochemistry of the contact system in vitro is well understood in the last five decades. The activated factor xii in turn activates factor xi to form contact product. The classic intrinsic pathway of coagulation is triggered by contact activatio n of the plasma protease factor fxii, followed by sequential proteolytic activation of fx1. Critical insights into the involvement of intrinsic pathway factors have been derived from the study of genespecific knockout animals and targeted inhibitors. The extrinsic pathway originates from factor vii fvii, which associated with. Coagulation cascade pathway, intrinsic pathway, extrinsic pathway created date. The intrinsic pathway, which is triggered by elements that lie within the blood inself intrinsic to the blood, occurs in the flowing way. Mechanisms of blood coagulation weber state university.
Inhibition by heparin of the human blood coagulation intrinsic pathway factor x activator received for publication, may 17, 1994, and in revised form, august 24, 1994. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin. Hemophilia and other intrinsic pathway defects hematology. Bleeding and blood clotting the extrinsic pathway of blood. Intrinsic pathways coagulation arterial thrombosis a n intricate mechanism has evolved in vertebrates to limit blood loss from damaged blood vessels through formation of clot hemostasis, while maintaining blood in a fluid state where the circulation is intact. Initiation of fibrin formation occurs at a site of blood vessel injury when plasma fviia binds to tissue factor tf, a membrane protein constitutively expressed by. Intrinsic pathway of coagulation and arterial thrombosis david gailani, thomas renne. Classification of coagulation factor as to their hemostatic functtion 6. Intrinsic pathway of blood coagulation pdf squarespace.
New findings on the roles of hydrophobic surfaces in contact activation of fxii revised the standard paradigm of the traditional intrinsic pathway. Components required for intrinsic pathway are entirely contained within the blood. Blood coagulation results from a series of proteolytic reactions involving the stepwise activation of coagulation factors. Nanoparticles and mimicking the intrinsic pathway with blood. Inmodelsofarterialinjury,fxiiorfxinullmiceareprotected from formation of platelet rich occlusive. Thrombin catalyzes the polymerization of fibrinogen into fibrin, which is the basic component of the blood clot. Laboratorybased interactions of the coagulation factors of the intrinsic pathway are illustrated in figure 331. Coagulationpathwayandphysiology 1 7 an excess of thromboplastin to anticoagulated plasmawasadirectmeasureoftheprothrombin amount in the plasmahence the name of the.
Damage to the vessel wall stimulates the activation of a cascade of clotting factors for the sake of simplicity we will not consider the individual factors. P3620the extrinsic and intrinsic pathways of coagulation. The current concept states that the intrinsic pathway is, in fact, an augmentation step. The contact activation system of intrinsic pathway of blood plasma coagulation is a plasma protease cascade potentiated by the assembly of activationcomplex proteins fxii, fxi, pk, and highmolecularweight kininogen in activating procoagulant surfaces through proteinsurface interactions. Intrinsic pathway the intrinsic pathway is activated by trauma inside the vascular system, and is activated by platelets, exposed endothelium, chemicals, or collagen. Bleeding and blood clotting the extrinsic pathway of. Upon the introduction of cells, particularly crushed or injured tissue, blood coagulation is activated and a fibrin clot is rapidly formed. Inhibition by heparin of the human blood coagulation.
Activation of coagulation factor x via the intrinsic pathway requires the assembly of factors ixa and vi11 on lipid membranes. Definition coagulation or clotting is defined as the process in which blood losses its fluid and becomes a jelly like mass few minutes after it is shed out ot collected in a container. Plasma coagulation an overview sciencedirect topics. Thus, the first day of warfarin therapy is a day of thrombotic diathesis. May 18, 2018 mechanism of blood coagulation is explained further in the coming slides. While this systemisessentialforminimizingbloodlossfromaninjuredbloodvesselhemostasis,italsocontributestopathologicfibrin. While this system is essential for minimizing blood loss from an injured blood vessel hemostasis, it also contributes to pathologic fibrin formation and platelet.
Intrinsic pathway with silica nanoparticles nanoparticles and blood coagulation megan nesland mentor. Intrinsic pathway of coagulation and arterial thrombosis. Intrinsic pathway an overview sciencedirect topics. The time course of clotting factor activation during coagulation was calculated, and the sensitivity of the kinetics due to a decrease or deficiency in the concentrations of coagulation proteins or their activities was studied. Mimicking the intrinsic pathway with silica nanoparticles nanoparticles and blood coagulation megan nesland mentor. It divides the coagulation into an extrinsic pathway activated by elements external to the blood and an intrinsic pathway initiated by blood components, which meet in a final common pathway with factor x fx activation. The pt and aptt test the integrity of the extrinsic and intrinsic pathways, respectively, while both pt and aptt are affected by defects in the final common pathway.
603 1236 76 1171 966 1177 227 581 1106 451 907 737 1561 581 565 1030 876 943 63 761 394 6 1619 886 1544 381 390 129 1061 1032 713 1579 882 22