Thrombin fibrin clots generation

The coagulation system that generates thrombin consists of intrinsic and extrinsic pathways. Both pathways are composed of a series of enzymatic reactions eventually producing thrombin, fibrin, and a stable clot. In parallel with the coagulation, the fibrinolytic system is activated locally. Plasminogen is converted to plasmin, which dissolves the fibrin mesh1 2 3 (Fig. 64—1). 

Thrombin generation assays (TGA) first evolved from standard clotting tests such as the PT, aPTT and TT, as they are essentially measuring the formation of thrombin through the formation of a fibrin clot. With the advancement of colorimetric assays and thrombin-specific peptide substrates, thrombin could be measured directly, eliminating interference from biological variables that often affect clot-based assays. In addition, clot-based assays are only truly reflective of the first burst of thrombin, whereas a measurement of the amount of thrombin is a better marker of clotting function. 

Both intrinsic and extrinsic pathways generate activated factor X. This protease, in turn, catalyses the proteolytic conversion of prothrombin (factor II) into thrombin (Ha). Thrombin, in turn, catalyses the proteolytic conversion of fibrinogen (I) into fibrin (la). Individual fibrin molecules aggregate to form a soft clot. Factor XHIa catalyses the formation of covalent crosslinks between individual fibrin molecules, forming a hard clot (Figures 12.3 and 12.4). 

Critical role of thrombin in thrombogenesis. Thrombin plays a critical and central role in thrombogenesis through platelet activation, fibrin generation, and clot stabilization at the site of arterial disruption, which are caused by percutaneous coronary intervention or plaque rupture in acute coronary syndromes. 

Hie serine protease thrombin takes a central position in the clotting system. It splits off fibrinopeptides A and B from the amino terminal ends of the a- and -chains of fibrinogen. The resulting fibrin monomer then undergoes polymerization to forma fibrin dot. Via activation of the clotting factors V and VIII, further thrombin is Generated from wothramhin. and via activation of blood dale lets and... 

Factor VII is the most sensitive of the vitamin K-dependent clotting factors. The mode of action is tissue factor-dependent activation of factors Xa and IXa on the surfaces of activated platelets (1). Factor Xa leads to thrombin generation and hemostasis, by converting fibrinogen to fibrin. This process is limited to the site of injury, since exposure of tissue factor from the subendothelial matrix has a role in the action of recombinant factor Vila, thereby reducing the risk of thromboembohc events (2). 

Thrombin then activates enzymes and factors that lead to the generation of yet more thrombin, an example of positive feedback. The extrinsic and in-uinsic pathways converge on a common sequence of final steps to form a clot comp>osed of the protein fibrin (Figure 10.26). Note that the active forms of the clotting factors are designated with a subscript "a. ... 

---