Plasma

The second crucial element of hemostasis—the fibrin clot—is the result of a complex interaction of many plasma proteins, proenzymes, and cofactors (10). The fibrin clot, the end product of the coagulation cascade, arises from and anchors the hemostatic plug. The cascade model of coagulation involves the activation of one of two pathways, the intrinsic pathway and the extrinsic pathway (Fig. 1). When these pathways were studied, it was thought that all the factors in the intrinsic pathway were within the vascular system, and that the tissue factors necessary to activate the extrinsic pathway were found outside the vascular space. Furthermore, it was believed that the two pathways were activated independently of one another. The current understanding of hemostasis helps appreciate that the intrinsic and extrinsic pathways are very much intertwined and that aOriginally, Immuno, Vienna, Austria; now Baxter Healthcare Corporation, Deerfield, IL.

FIGURE 1 ■ Cascade model for coagulation.

Converting fibrinogen to fibrin, thrombin plays an extremely critical role in the process of fibrin clot development.

In the presence of ionized calcium, thrombin activates factor XIII to XIIIa. Factor XIIIa converts the noncovalent bonds between the fibrin fibers into covalent bonds and creates stable and insoluble fibrin clot by cross-linking the fibrin molecules.

Fibrin sealant may be produced from pooled sources or a single donor. The use of pooled blood products is the current basis for the commercially available fibrin sealant. The single-donor blood can be allogenic or autologous.

all clotting factors are in some way interrelated. Nevertheless, each pathway, including that initiated by platelets, results in the conversion of factor X to activated factor X. Factor Xa as well as activated factor V (Va) converts prothrombin to thrombin. Converting fibrinogen to fibrin, thrombin plays an extremely critical role in the process of fibrin clot development.

Fibrinogen, a soluble blood component, comprising 0.2% of whole blood volume is a glycoprotein comprising three pairs of polypeptide chains called Aa, Bp and y. The central domains of the fibrinopeptide A and B are cleaved from their respective Aa and Bp chains by the serine protease thrombin. This enzymatic cleavage forms the fibrin monomers due to a change in the charge and conformation of fibrinogen (6). Hydrogen bonds and electrostatic reactions polymerize the fibrin monomers into unstable and soluble fibrin fibers.

In the presence of ionized calcium, thrombin activates factor XIII to XIIIa. Factor XIIIa converts the noncovalent bonds between the fibrin fibers into covalent bonds and creates stable and insoluble fibrin clot by cross-linking the fibrin molecules (11).

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