Contact activation pathway intrinsic

Initiation of blood coagulation (clotting) occurs through the contact activation pathway (intrinsic pathway) and the tissue factor (TF) pathway (extrinsic pathway). The contact activation pathway is quantitatively the most important, but is much slower to initiate the TF pathway is considered to be the primary pathway for the initiation of blood coagulation and affords a more rapid response (the so-called thrombin burst), which augments the contact activation pathway. Both pathways share a common pathway that converges at factor X with the production of thrombin (Figure 11.1). 

The contact activation pathway (intrinsic) begins with formation of the primary complex on collagen by high-molecular weight kininogen, prekalhkrein and factor XII (Hageman factor). 

The coagulation pathway can be activated by one of two pathways the extrinsic (tissue factor) pathway or the intrinsic (contact activation) pathway (Figure 13-1). The main coagulation pathway in vivo is the tissue factor pathway. Tissue factor is exposed by damaged endothelium. This exposed tissue factor binds and activates factor VII, which, in turn, activates factor X. Factor Xa results in the generation of a thrombin (factor lla) burst. Thrombin, in turn activates factors XI, VIII, and V, leading to the further generation of thrombin and clottable fibrin. Additionally, the tissue factor Vila complex activates factor IX, which further contributes to the activation of factor X. 

Stronger binding affinity.Factor XII is activated to factor Xlla in the Vroman layer which marks the initiation of the Contact Activation Pathway. Activated factor Xlla converts factor XI to active factor XIa, which in turn activates factor IX to factor IXa. Factor IXa, along with factor VIII, activates factor X to factor Xa. This is the last step of the intrinsic pathway, which is the same as that in the extrinsic pathway. ... 

The test-tube model of coagulation consists of the extrinsic pathway, the intrinsic pathway and a common pathway as shown in Figure 19.3. Damage to a blood vessel exposes TF to the blood, initiating the TF pathway or extrinsic pathway. TF binds zymogen and factor VII to produce activated factor Vila. Factor Vila activates factor X to factor Xa in the common pathway as well as factor IX to factor IXa in the contact activation (intrinsic) path-way,2o.2i jjjjg jg jgygj Qf positive feedback amplification. Activated... 

Blood clotting at artificial surfaces has been, and still is, a major problem in extracorporeal blood treatments. Within milliseconds fi om blood contact with an artificial surface, plasma proteins (e.g., fibrinogen) adsorb on it (Basmadjian et al. 1997), the intrinsic coagulation pathway is activated, platelets adhere to the surface or aggregate and release factors that further activate the intrinsic coagulation pathway, thus promoting thrombogenesis. 

The intrinsic pathway appears to be initiated when factor XII is activated by contact with surface proteins exposed at the site of damage. High molecular mass kininogen also appears to form part of this initial activating complex (Figure 12.2). 

Figure 10.37. Blood-Clotting Cascade. A fibrin clot is formed by the interplay of the intrinsic, extrinsic, and final common pathways. The intrinsic pathway begins with the activation of factor XII (Hageman factor) by contact with abnormal surfaces produced by injury. The extrinsic pathway is triggered by trauma, which activates factor VII and releases a lipoprotein, called tissue factor, from blood vessels. Inactive forms of clotting factors are shown in red their activated counterparts (indicated by the subscript "a") are in yellow. Stimulatory proteins that are not themselves enzymes are shovm in blue. A striking feature of this process is that the activated form of one clotting factor catalyzes the activation of the next factor.

The slower intrinsic mechanism first described in 1964 47,548 consists of a cascade involving six proteases (Fig. 12-17, left side). Again, autocatalytic cycles are present in the activation by Xlla of both prekallikrein and XII and in activation by thrombin of factors XI and VIII. This intrinsic pathway is initiated by the serine protease proenzymes prekallikrein and factor XII together with the accessory protein high-molecular-mass-H- kininigen. 49 Activation occurs when blood contacts surfaces such as glass or kaolin (a clay). 47,548,550 Factor XI can also be activated by thrombin. Heredity absence of factor XI leads to bleeding problems, especially... 

Two pathways initiate a fibrin clot. Extrinsic path is mediated by tissue factor, also called thromboplastin. This membrane protein is exposed when pericytes are damaged. It binds to factor Vila in blood. Factor Vila is a protease and the phospholipid-VIIa-TF complex activates (converts) factor X by cleaving it to Xa. Intrinsic path is initiated by factor XII (Hageman factor), whose conformation is changed to a protease (XHa) by contact with a negatively charged surface such as RNA from damaged or necrotic cells. 

Functional evaluation of the intrinsic and final common pathways. Activation of the contact phase is by addition of a surface reagent to a plasma sample. 

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