Fibrinogen rate

The acute-phase response is characterised by the enhanced (two- to threefold) synthesis of a number of proteins, such as antiproteinases, complement components, fibrinogen and ceruloplasmin, which are normally synthesised at fairly low rates. The rate of synthesis of some proteins is enhanced 100-1000-fold - for example, C-reactive protein, a-macroglobulin and acid-1-glycoprotein. Thus, serum levels of these proteins serve as indicators of disease. 

Figure 3.15 Chromatogram of fibre-type proteins on polystyrene gels having different pore sizes. Column A, PLRP-S 300 A, 15 cm x 4.6 mm i.d. B, PLRP-S 1000 A (polystyrene gel), 15 cm x 4.6 mm i.d. eluent, 15 min linear gradient from 20% of 0.25% trifluoroacetic acid to 60% of 0.25% trifluoro-acetic acid in 95% aqueous acetonitrile flow rate, 1.0 ml min-1 detection, UV220 nm. Peaks 1, collagen (Mr 120 000) and 2, fibrinogen (Mr 340 000). (Reproduced by permission from Polymer Laboratories data)...

The rise in fibrinogen causes erythrocytes to form stacks (rouleaux) that sediment more rapidly than individual erythrocytes. Hence, the erythrocyte sedimentation rate is a simple test for prolonged low-level infection. 

Changes in serum proteins and other effects on endocrine function (see above) must be taken into account when thyroid, adrenal, or pituitary function is being evaluated. Increases in sedimentation rate are thought to be due to increased levels of fibrinogen. 

The kinetics of the lytic effect displayed by the complexes of immobilized heparin with thrombin and fibrinogen, in distinction from those with plasmin, are described by their saturation curves. The observed slowing down of the dissolution of unstabilized fibrin is probably due to the inhibiton of the lytic activity of the complexes by the soluble products of the reaction. In fact, as it was shown in Ref. 106, further addition of immobilized heparin-protein complex to partially hydrolyzed fibrin results in a complete recovery of the dissolution rate. 

The observed enhancement of the catalytical efficiency of immobilized trypsin in the presence of immobilized heparin was shown to be due to the association of the products of fibrinolysis (as in the case of fibrinogen) which removed them out of reach of immobilized trypsin 137>. In fact, as is seen from Fig. 9, the lysis rate gradually decreases as the reaction products are accumulated, i.e., accumulation of the lysis products causes the poisoning of the catalyst. Addition of new polymer, but this time of that containing immobilized heparin only, again leads to an increase of the lysis rate (Fig. 10). 

The considerable body of evidence that glucocorticoids can cause increased rates of vascular mortality and the underlying mechanisms (increased blood pressure, impaired glucose tolerance, dyslipidemia, hypercoagulability, and increased fibrinogen production) have been... 

Substitution of particular amino acids in the fibrinopeptides and at thrombin s cleavage sites in recombinant fibrinogen has been used to understand thrombin specificity, the relative rates of fibrinopeptide cleavage, and effects on polymerization. If fibrinopeptide B is replaced with a fibrinopeptide-A-like peptide, fibrinopeptide release is similar to release from the Aa chain (Mullin et al., 2000). Thus, the ordered release of fibrinopeptides is dictated by the specificity of thrombin for its substrates. 

There is evidence for the involvement of the N-terminal B/3 chain in fibrin polymerization (Pandya et at, 1985 Siebenlist et al., 1990). A recombinant fibrinogen with His substituted for Arg at the B/3 thrombin-cleavage site led to a 300-fold decrease in the rate of fibrinopeptide B release, whereas the rate of fibrinopeptide A release was normal (Moen et al., 2003). As a consequence, thrombin- or batroxobin-catalyzed or desA monomer polymerization was impaired, due to the histidine substitution itself. Thus, it appears that the N-terminus of the B/3 chain is involved in the lateral aggregation of normal desA protofibrils. 

Blomback, B., Carlsson, K., Fatah, K., Hessel, B., and Procyk, R. (1994). Fibrin in human plasma Gel architectures governed by rate and nature of fibrinogen activation. Thromb. Res. 75, 521-538. 

Patients with nephrotic syndrome often have markedly increased erythrocyte sedimentation rate (ESR) owing to high levels of fibrinogen. Thus, high ESR in nephrotic patients does not necessarily mean acute-phase reaction. 

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