Properties of Fibrin Clots

When the conversion of fibrinogen to fibrin has reached completion, the properties of the resulting clot are found to be markedly dependent 

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The properties of fibrin clots vary considerably between those of two... 

The mechanical properties of fibrin are essential for its functions in hemostasis and wound healing, since the clot must stop bleeding and yet allow the penetration of cells. The mechanical properties of a thrombus will determine how it responds to flowing blood, including elastic or plastic deformation and embolization. Epidemiological studies have revealed a relationship between myocardial infarction and clot stiffness (Fatah et al., 1996 Scrutton et al., 1994). 

Fibrin is a viscoelastic polymer, which means that it has both elastic and viscous properties (Ferry, 1988). Thus, the properties of fibrin may be characterized by stiffness or storage modulus (representing its elastic properties) and creep compliance or loss modulus/loss tangent (representing its inelastic properties). These parameters will determine how the clot responds to the forces applied to it in flowing blood. For example, a stiff clot will not deform as much as a less stiff one with applied stress. 

The origin of clot elasticity is unknown, although it cannot be rubberlike because the clot has very different structural and mechanical properties (Ferry, 1988). Comparisons of the mechanical properties of clots made under a variety of conditions correlated with the clot structures demonstrate empirical relationships that provide some clues to this longstanding puzzle (Ryan et al., 1999). The most likely explanation for the inelastic properties of fibrin is the slippage of protofibrils past each other, but there may be some role of breakage and reformation of noncovalent bonds (Weisel, 2004b). 

Our present picture of the nature of fibrin clots is due primarily to the work of Terry and Morrison (1947a,b). The ine and coarse clots, referred to in Section 4 are repre.sented schematically in Tigs. 90 and 91 (see Section 4 for a discussion of the properties of these clots). A further description of the properties of these two types of clots has been given by Terry (1948). 

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

The amino acid sequences of haptides comprise hydrophobic and cationic residues with a net charge of +4 to +5 per 19 to 21 amino acids. It was proposed that haptides could be attracted to the anionic liposomes as well as the anionic cell membrane and that the hydrophobic properties of the haptide facilitate membrane translocation (106). Haptide uptake was reported to be energy independent, occurring at 4°C. The advantage of this peptide compared to CPP such as TAT and Antp, is that, unlike the virus-derived peptides, the haptides are not recognized as foreign antigens and do not induce cell transformation (106). However, haptides have also been found to accelerate fibrin clot formation and lack cell specificity (106). 

Each a chain contains potential glutamine acceptor sites at 221, 237, 328, and 366, and donor sites at lysine 508, 539, 556, 580, and 601 (Greenberg et al., 2003 Matsuka et al., 1996). Since the aC domains associate even in the absence of crosslinking, these interactions probably bring acceptor and donor sites in proximity, facilitating the formation of the isopeptide bonds. These bonds create a covalendy connected network of aC domains, although litde is known of its structure. In addition, there are lesser amounts of 7 trimers, tetramers, and 07 complexes. Factor XIII polymorphisms can have effects on the structure and properties of the fibrin clot (Ariens et al., 2002). 

Some proteins, such as plasma fibronectin and albumin, interact with fibrin to alter clot structure and properties, although the former becomes crosslinked to fibrin while the latter does not. As a result of these and other interactions, fibrin clots formed in plasma have very different properties than those made with purified proteins (Blomback et al, 1994 Carr, 1988 Shah et al., 1987). Albumin has significant effects on the extent of lateral aggregation, yielding either thicker or thinner fibers depending on its concentration and other experimental conditions (Galanakis et al, 1987 Torbet, 1986). 

A fibrin clot containing adsorbed plasmin inhibitors is difficult to define in a chemical or physical sense. Generally, when enzyme reactions occur at surfaces, the porosities and adsorption properties erf which are variable, the reproducibility of enzyme assay methods is questionable. The proteinoses, to which belong the most important pharmaceutical enzymes, may present some difficulties when natural substrates (protein ) are prescribed. Here, the application of a parallel run with a reference standard is recommended. 

In humans, dextran administration is associated with a decrease in factor VIII activity, decreased fibrin clot formation and dilutional coagulopathy (Roberts Bratton 1998). Dextran 70 inhibits equine platelet aggregation in vitro (Heath et al 1998) but other effects on hemostasis have not been investigated. Dextran 70 has been used for its presumed antithrombotic properties in horses with a clinical diagnosis of verminous aneurysm (Table 17.9) (Greatorex 1977). Dextran 70, when combined with hypertonic saline, resulted in a... 

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