Thrombin action

In the case of platelet-derived factor XIII, the resultant product (a )2, is the activated form. Thrombin action on plasma-derived factor XIII generates an a 2jfi2 dimer, which is devoid of transglutaminase activity. However, in the presence of Ca +, the a P chains dissociate, yielding the biologically active a 2. 

Id vivo, the infusion of small amounts of thrombin (<200 NIH-U/kg/h) causes defibrinogenation. Because of the slow transformation of fibrinogen, the fibrin monomers formed are eliminated via reactive fibrinolysis and RES without precipitation of fibrin. Upon infusion of higher amounts of thrombin, these clearance mechanisms fail bo offset the thrombin action, which then leads to the formation of microthmmbi in the peripheral circulation. Correspondingly, the bolus injection of 1500 NIH-U thrombin/kg caused death of the experimental... 

GeHcfi c Studies Revealing the Tioo Branches of Thrombin Action... 

Components/ mechanism of action Human plasma, fibrinogen and thrombin, virally inactivated, hemostat, sealant. Autologous fibrinogen -t-platelet-rich plasma, hemostatic gel. Bovine collagen, bovine thrombin, plus autologous human plasma, hemostatic agent. Bovine collagen and bovine thrombin. Expands 20% which aids in hemostatic effect. 

Fibrin is an elastic filamentous protein elaborated from its precursor, fibrinogen, which is present in plasma at high concentration. Fibrin is formed in response to the actions of thrombin. Thrombin cleaves small peptides from the fibrinogen molecule, forming fibrin monomers that will begin to polymerize and become crosslinked. 

Inhibits platelet aggregation by increasing levels of cAMP Binds protein C, which is then cleaved by thrombin to yield activated protein C this in combination with protein S degrades factors Va and Villa, limiting their actions Activates plasminogen to plas-min, which digests fibrin the action of t-PA is opposed by plasminogen activator inhibitor- (PAI-1)... 

This consists of cellulosic material which has been partially oxidized. White gauze is the most common form, although lint is also used. It can be absorbed by the body in 2-7 weeks, depending on the size. Its action is based prineipally on a meehanieal effect and it is used in the dry state. Since it inactivates thrombin, its activity cannot be enhanced by thrombin ineorporation. 

The thrombin receptor is unusual in that the receptor is activated by the enzymatic action of thrombin which cleaves the N-terminus of the receptor leaving the receptor constitutively active. 

FIGURE 7-7. Mechanism of action of direct thrombin inhibitors. 

The concept that different structural domains on the heparin chains are principally involved for optimal activity in the foregoing interactions could not be perceived in early work on structure-activity correlations, because the activity of heparin has been most frequently evaluated only with whole-blood-clotting tests (such as the U.S.P. assay). Development of assays for specific clotting-factors (especially Factor Xa and thrombin) has permitted a better insight into the mechanism of action of heparin at different levels of the coagulation cascade. 

By far the most widely measured marker of hemostatic activation is D-dimer, which is a product formed by the action of plasmin on cross-linked fibrin (95). D-dimer levels in plasma are generally elevated in DIC. The consumption of platelets and coagulation proteins as a result of thrombin generation leads to the deposition of fibrin thrombi at multiple organ sites. This triggers fibrinolysis with an increase in the formation of fibrin degradation products, which can cause bleeding at multiple sites. Because DIC can have a variety of causes and may coexist with systemic fibrinolysis, such as in pulmonary embolism or deep vein thrombosis, the d-Dimer test is not specific for DIC (95). 

Factor XIa, in turn, activates factor IX. Factor IXa then promotes the activation of factor X, but only when it (i.e. IXa) is associated with factor Villa. Factor Villa is formed by the direct action of thrombin on factor VIII. The thrombin will be present at this stage because of prior activation of the intrinsic pathway. 

Walker, C. and Royston, D. 2002. Thrombin generation and its inhibition a review of the scientific basis and mechanism of action of anticoagulant therapies. British Journal of anaesthesia 88(6), 848-863. 

Figure 17.2 The intrinsic and extrinsic pathways involved in blood clotting. Both pathways converge to activate thrombin. Solid arrows represent biochemical conversions whereas dotted arrows represent either catalytic or activating actions. Fibrin is formed as monomers which polymerise to form fibrils. Within the fibrils, the fibrin monomers associate laterally which is facilitated by active XIII (ie Xllla). Thrombin activates XIII.

Following injury to blood vessels, hemostasis ensures that blood loss is minimized. Initially, thrombocyte activation leads to contraction of the injured vessel and the formation of a loose clot consisting of thrombocytes (hemostasis). Slightly later, the action of the enzyme thrombin leads to the formation and deposition in the thrombus of polymeric fibrin (coagulation, blood clotting). The coagulation process is discussed here in detail. 

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