Fibrin network

Since arterial emboli formation involves platelet aggregation and leukocyte and erythrocyte inhltration into the fibrin network, the treatment and prophylaxis of arterial thrombi are more difficult. Arterial embolism is treated more successfully with heparin than with the oral anticoagulants. Anticoagulants are useful for prevention of systemic emboli resulting from valvular disease (rheumatic heart disease) and from valve replacement. 

Fibrin polymerization is initiated by the enzymatic cleavage of the fibrinopeptides, converting fibrinogen to fibrin monomer (Fig. 1). Then, several nonenzymatic reactions yield an orderly sequence of macromolec-ular assembly steps. Several other plasma proteins bind specifically to the resulting fibrin network. The clot is stabilized by covalent ligation or crosslinking of specific amino acids by a transglutaminase, Factor XHIa. 

Collet, J.-P., Park, D., Lesty, C., Soria, J., Soria, C., Montalescot, G., and Weisel, J. W. (2000). Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed Dynamic and structural approaches by confocal microscopy. Arterioscler. Thromb. Vase. Biol. 20, 1354-1361. 

Ferry, J. D. (1988). Structure and rheology of fibrin networks. In Biological and Synthetic Polymer Networks (O. Kramer, Ed.), pp. 41-55. Elsevier, Amsterdam. 

Sakharov, D. V., Nagelkerke, J. F., and Rijken, D. C. (1996). Rearrangements of the fibrin network and spatial distribution of fibrinolytic components during plasma clot lysis. Study with confocal microscopy. / Biol. Chem. 271, 2133-2138. 

A red thrombus can form around a white thrombus as mentioned above or de novo in low-pressure veins, initially by adherence of platelets (as in arteries) but followed promptly by the process of blood coagulation so that the bulk of the thrombus forms a long tail consisting of a fibrin network in which red cells are enmeshed. These tails become detached easily and travel as emboli to the pulmonary arteries. Such emboli often arise from a deep venous thrombosis (DVT)—a thrombus in the veins of the legs or pelvis. Although all thrombi are mixed, the platelet nidus dominates the arterial thrombus and the fibrin tail the venous thrombus. Arterial thrombi cause serious disease by producing local occlusive ischemia venous thrombi, by giving rise to distant embolization. 

There are several self-assembling macromolecules that are of interest to us in this text. They include (1) collagen, the primary structural material found in the extracellular matrix (2) actin, a component of the cell cytoskeleton that is involved in cell locomotion and in formation of the thin filaments of muscle (3) microtubules, which are involved in cell mitosis, movement, and organelle movement and finally (4) fibrinogen, which forms fibrin networks that minimize bleeding from cut vessels. Self-assembly is important in these systems because the function of these macromolecules can be modified via processes that increase the molecular axial ratio and hence decrease the solubility. 

During platelet plug formation, the fibrinolytic pathway is locally activated. Plasminogen is enzymatically processed to plasmin (fibri-nolysin) by plasminogen activators present in the tissue. Plasmin interferes in clot propagation and dissolves the fibrin network as wounds heal. At present, a number of fibrinolytic enzymes are available for treatment of myocardial infarctions or pulmonary emboli (see p. 201). 

A variety of chemical agents has been used to induce thrombosis in animals. Topical FeCU was described by Reimann-Hunziger (1944) as thrombogenic stimulus in veins. Kurz et al. (1990) showed that the thrombus produced with this method in the carotid arteries of rats is composed of platelets and red blood cells enmeshed in a fibrin network. This model is used as a simple and reproducible test for evalua-... 

Thrombin Activates Infegrm, and This Activalion Provokes Binding of Platelets to the Fibrin Network and to the Ruptured Biood... 

Veldman, F.J., Nair, C.H., Vorster, H.H., Vermaak, W.J., Jerling, J.C., Oosthuisen, N. and Venter, C.S. 1999. Possible mechanisms through which dietary pectin influences fibrin network architecture in hypercholesterolemic subjects, Thrombosis Res., 93(6) 253-264. 

The first event that generally occurs after blood contacts a polymer surface is the formation of a protein layer at the blood-polymer interface (1). The formation of this protein layer is followed by the adherence of platelets, fibrin, and possibly leukocytes (2). Further deposition with entrapment of erythrocytes and other formed elements in a fibrin network constitutes thrombus formation. The growth of the thrombus eventually results in partial or total blockage of the lumen unless the thrombus is sheared off or otherwise released from the surface as an embolus (3). Emboli can travel downstream, lodge in vital organs, and cause infarction of tissues. The degree to which the polymer surface promotes thrombus formation and embolization, hemolysis, and protein denaturation determines its usefulness as a biomaterial (4). 

Figure 22. Fibrinogen-coated PVC after 15 min of blood contact (representing time of maximum deposition). Extensive fibrin network basal to attached platelets and platelet clumps is shown. Fibrin is the predominant species present.

The blood clot formed in a test tube is strikingly different from a thrombus deposit formed in vivo in the vascular system. A clot in a test tube consists of a fibrin network in which red cells, white cells, and relatively small numbers of platelets are found. On the other hand, an in vivo thrombus deposit consists of large amorphous masses of platelets, surrounded by white cells with a few red cells. However, it is possible to form deposits closer to thrombi rather than to blood clots in vitro by using circulating plastic loops in which the blood is in motion during coagulation. ... 

Bleeding from injured blood vessels can be arrested by the activation of the hemostatic mechanism [24]. However, an artificial device surface placed in contact with blood can disturb the balance of this mechanism [24]. Excessive blood clotting with increased risk of embolization can occur due to the adhesion of platelets and lenkocytes to device surface and the formation of fibrin network following the... 

When blood is placed in contact with any foreign materials, it is known that protein adsorption is occurred first and followed by platelet adhesion and cascade reaction of coagulation factors and their subsequent activations, which lead to thrombus formation resulted into the formation of fibrin network structure. 

Koutsioubas A, Profumo A, Trevarin D et al (2014) A comprehensive mechanism of fibrin network formation involving early branching and delayed single-to double-strand transition from coupled time-resolved X. J Am Chem Soc 136 5376-5384... 

Kim OV, Litvinov RI, Weisel JW, Alber MS (2014) Structural basis for the nonlinear mechanics of fibrin networks under eompression. Biomaterials 35 6739-6749... 

PVS was grafted onto the surface of polyurethane, polystyrene, and poly(ethylene terephthalate) films by the plasma-pietreated method. Activated partial thromboplastin time (APTT) of PVS-grafted polyurethane films was greatly prolonged, and a fibrin network was not found at on the film grafted with PVS in... 

A and B, and to produce a fibrin monomer. The new N-termini of the a and 3 chains now bind to the terminal domain of a different fibrin monomer causing the spontaneous polymerization to form insoluble fibrin polymers. This fibrin network is further strengthened by the introduction of covalent cross-links by factor Xllla. 

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