The contact activation pathway

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). 

PrekaUikrein is converted to kaUrkrem and factor XII is activated to Xlla. Factor Xlla activates Xl-XIa, which activates factor IX, which together with its co-factor Villa forms the tenase complex, resniting in activation of factor X. The minor role that the contact activation pathway has in initiating clot formation can he Ulnstrated hy the fact that patients with severe deficiencies of factor Xn, kininogen and prekaUikrein do not exhibit a bleeding disorder. 

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 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. 

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... 

The importance of FAK is underlined by the finding that cells expressing a constitutively active form survive in suspension even though they are homeless. Here, the protein kinase is active regardless of the failure to make contact with an extracellular matrix. Rescue from apoptosis also occurs when cells express constitutively activated oncogenic forms of Ras or Src and thus activate Plj-kinase and the MAP kinase pathway. Unlike FAK, these not only prevent apoptosis but also promote proliferative signals that result in tumor formation. 

Hydrothermal activity is also of interest to geological and physical oceanographers. Since we have not yet drilled through the crust to permit direct observation of the mantle, hydrothermal systems provide the closest contact that scientists have yet had with magma. For physical oceanographers, some of the hydrothermal emissions, such as He and Mn, can be used as tracers of the rate and pathways of water-mass motion as already illustrated in Figure 11.19. 

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