Fibrinogen sedimentation

Primary blood components iaclude plasma, red blood cells (erythrocytes), white blood cells (leukocytes), platelets (thrombocytes), and stem cells. Plasma consists of water dissolved proteias, ie, fibrinogen, albumins, and globulins coagulation factors and nutrients. The principal plasma-derived blood products are siagle-donor plasma (SDP), produced by sedimentation from whole blood donations fresh frozen plasma (FFP), collected both by apheresis and from whole blood collections cryoprecipitate, produced by cryoprecipitation of FFP albumin, collected through apheresis and coagulation factors, produced by fractionation from FFP and by apheresis (see Fractionation, blood-plasma fractionation). 

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. 

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. 

F, is smaller than V, a low /3-value will also result. This illustration by no means implies that fibrinogen must require two equivalent ellipsoids for viscosity and sedimentation. It is not clear why the 3-function for fibrinogen behaves abnormally, if the other weight of evidence is accepted as a correct description of the molecule. It is even possible that the conclusion of Siegel et al. (1953) may eventually turn out to be the correct one. There is need for more extensive tests for the j8-function. 

By monitoring the erythrocyte. sedimentation rate (ESR). This reflects fibrinogen and immunoglobulin concentration. ESR changes slowly, and is used to monitor the inflammatory process over weeks rather than days. 

The clinician can determine whether a patient such as Katta Bolic is j mounting an acute phase response to some insult, however subtle, by deter- mining whether several unique acute phase proteins are being secreted by the liver. C-reactive protein, so named because of its ability to interact with the C-polysaccharide of pneumococci, and serum amyloid A protein, a precursor of the amyloid fibril found in secondary amyloidosis, are elevated in patients undergoing the acute phase response and as compared with healthy individuals. Other proteins normally found in the blood of healthy individuals are present in increased concentrations in patients undergoing an acute phase response. These include haptoglobin, certain protease inhibitors, complement components, ceruloplasmin, and fibrinogen. The elevated concentration of these proteins in the blood increases the erythrocyte sedimentation rate (ESR), another laboratory measure of the presence of an acute phase response. 

On the addition of oxalate, blood separates into two layers. A dark red layer contains the blood corpuscles and a yellowish layer contains the plasma and plasma proteins. The plasma proteins can then be separated by fractional precipitation with ammonium sulfate solution. A 20%-25% ammonium sulfate solution will precipitate fibrinogens a 33% solution, globulin and a 50% solution, pseudoglobulin while albumins only precipitate at very high ammonium sulfate concentration. Ultracentrifuge measurements enable four components (X, A, G, M) with different sedimentation coefficients to be differentiated and isolated ... 

Determination of molecular symmetry. Molecular symmetry of P. can be determined from measurements of viscosity, streaming birefringence, rates of sedimentation and diffusion, or directly by electron microscopy, For a known M, the frictional coefficient can be calcnlated from ultracentrifugal measurements, e.g. from the sedimentation /= [Mfl - vp)]/S, where v is the partial specific volume, p is the density and S is the sedimentation constant. The axial ratio a/b of a P. can be derived from the frictional ratiowhereis the/of a spherical molecule. The value of a/b for most globular P. is between 2 and 20, and greater than 20 for fibrous R, e, g. the axial ratio of fibrinogen is 30. 

Fig. 72. Sedimentation constants reduced to water at 20°C. plotted against (initial) concentration of fibrinogen for fast and slow components in inhibited clotting systems and for fibrinogen. All points in the upper two diagrams refer to an average glycol concentration of 0.38 M. In the lower diagram, solid circles pertain to 0.38 M glycol, open circles to no added glycol (Shulman and Ferry, 1961).

Fig. 83. Sedimentation patterns of protein species involved in the fibrinogen-fibrin conversion. The solvent in all cases is 1 Af NaBr. A fibrinogen, F, at pH 6.3 B Fibrin monomer, f, at pH 5.3 (the same pattern is obtained either for a solution of fibrin at pH 6.3 or for a mixture of thrombin and fibrinogen at pH 5.3) C fast and slow peak pattern in a system of intermediate polymers (the same pattern is obtained either for a solution of fibrin at pH 6.1 or for a mixture of thrombin and fibrinogen at pH 6.1) (Donnelly et al., 1955).

Something is known as to the results of necrosis of tissue in geneniJ, such as the elevated cholesterol and lipid levels, elevated erythrocyte sedimentation rate, and shifts in the serum proteins such as the increase of the globulin and fibrinogen content and a decrease of the albumin globulin ratio. 

A plasma protein, synthesized by the liver. It is converted to fibrin during the coagulation process to form the matrix of the blood clot. Thrombin is required for this conversion. Increased plasma fibrinogen levels are found after trauma and in many inflammatory diseases. The increases in the plasma fibrinogen level account, at least in part, for the increased erythrocyte sedimentation rate in such cases. Decreased plasma levels are found in liver diseases and in the genetic defect congenital hypo-fibrinogenaemia. 

In an observational study in London, 20 adults (12 male, mean age 52.6 years) with autoimmune neurological disease were prospectively evaluated while xmdergoing a 1- to 5-day course of high-dose IVIG infusions. There was a rise in plasma viscosity (associated with daily dose and entire course), serum interleukin-6 and erythrocyte sedimentation rate but not corresponding increase in blood pressure, C-reactive protein or fibrinogen. One of twenty patients developed IgG and IgM anticardiolipin antibodies [59 ]. 

From studies of double refraction of flow (Edsall, Foster, and Schein-berg, 1947), and sedimentation and viscosity (Oncley, Scatchard, and Brown, 1947), the dimensions of the fibrinogen molecule considered as an elongated ellipsoid of revolution have been estimated to be 35 A. X 700 A., with a molecular weight of about 500,000 assumption of the shape of a cylindrical rod would probably not alter these figures greatly. 

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