Blood clotting fibrin clot, control

Formation of a blood clot involves a complex cascade of enzymatically controlled reactions the penultimate step of which is the formation of thrombin. Thrombin then cleaves peptides from fibrinogen to form fibrin monomers that associate to form the fibrin clot. Fibrin clot formation is a carefully poised process whereby a relatively minor injury will not allow excessive bleeding and result in death and whereby excessive clot formation will not block blood flow and result in death. As will be seen by examination of the relevant molecular structures, regardless of the balance struck, the key process of clot formation is the hydrophobic association of fibrin monomers. In demonstrating this perspective, the same T,-based mean residue hydrophobicity plot will be used as was used above in Figure 7.9 for understanding the hydrophobic association of hemoglobin subunits. 

Fig. 11.13 Coagulation flow chart Blood coagulation events are divided into initiation, extrinsic and intrinsic path activation, and the common path to fibrin. Controls are fibrinolysis as healing begins and inhibition of clotting factors in a healthy (uninjured) blood vessel. Diseases are excessive bleeding (hemophilia) and excessive clotting (Original figure)...

There is a fine line between hemorrhage and thrombosis. Clots must form rapidly yet remain confined to the area of injury. What are the mechanisms that normally limit clot formation to the site of injury The lability of clotting factors contributes significantly to the control of clotting. Activated factors are short-lived because they are diluted by blood flow, removed by the liver, and degraded by proteases. For example, the stimulatory proteins factors Va and Villa are digested by protein C, a protease that is switched on by the action of thrombin. Thus, thrombin has a dual function it catalyzes the formation of fibrin and it initiates the deactivation of the clotting cascade. 

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