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The influence of cryoglobulins on the temperature-dependent erythrocyte aggregation in vitro by backscattering nephelometry.

Nephelometry technique was used to register the alterations of the scattering signal from a whole blood sample due to erythrocyte aggregates in stasis and under controlled shear stress. The measured parameters were: the characteristic times of linear and three-dimensional aggregates formation, and the strength of aggregates of different types. These parameters depend on the sample temperature in the range of 2/50 degrees C. Temporal parameters of the aggregation process strongly increase (by 3 times) at temperature 45 degrees C. For samples of normal blood the aggregates strength parameters do not significantly depend on the sample temperature, whereas for blood samples from patients with cryoglobulinemia high increase of the strength of both three-dimensional and linear aggregates and decrease of time of linear aggregates formation at low temperature of the sample (4 degrees C) was observed. The difference of these parameters of the pathological blood from that of the normal at room temperature was quite opposite. Possible reasons of such behavior of aggregation state of blood and explanation of the observed effects are suggested.

Cryoglobulinemia↗

Increased erythrocyte aggregation as an indicator for an aggressive clinical course in Behçet's disease: a prospective study.

OBJECTIVE: Changes in blood rheology, especially increased erythrocyte aggregation (EA) might play an important part in the development of arterial and venous thrombotic lesions. A prospective study was designed to evaluate EA in patients with Behçet's disease (BD) and to see if this parameter is predictive for the future development of vascular complications, such as deep vein thrombosis of various organ systems and uveitis. METHODS: EA was measured by a photometric Myrenne aggregometer in 38 patients with BD at the time of initial diagnosis and in 40 age and sex matched healthy controls (HC). RESULTS: During a median follow up period of 13.5 months, 13 patients developed vascular-ocular complications (eight deep vein thrombosis, nine uveitis, and four both deep vein thrombosis and uveitis). Patients were further divided into two groups: BD-a with mucocutaneous symptoms and arthritis only; BD-b with associated vascular-ocular complications. EA values at high shear rate (M) and at low shear rate (M1) were compared among the groups. CONCLUSION: EA values at M and M1 were significantly higher in BD-b than BD-a and HC (p < 0.001). These results suggest that determination of EA rates might be useful to identify subgroups who are likely candidates for developing vascular-ocular complications in BD and management of factors known to affect blood rheology might be beneficial.

Adult↗

Mechanism of erythrocyte aggregation and sedimentation.

Unstirred suspensions of erythrocytes form stable spherical aggregates of uniform size. The radius of the spheres depends upon the suspending medium and the hematocrit. Erythrocyte suspensions will undergo sedimentation only after these aggregates are formed. Aggregation is a two-step process: first, erythrocytes associate in long chains (rouleau formation). Next, these chains form spheres of uniform size. The requirements for this well-defined process are an electrolyte and a neutral or negatively charged macromolecule in the solution and a metabolically active red cell. If these conditions are not met, red cells either will not aggregate at all or will form amorphous aggregates. Rouleau formation and sedimentation are inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, an inhibitor of anion transport, but not by ouabain, a cation transport inhibitor. The kinetics of erythrocyte sedimentation reflects the aforementioned mechanism: no sedimentation occurs during rouleau formation. Once the spheres of uniform size are formed, they will settle according to the Einstein-Stokes equation. In this model, parameters of sedimentation kinetics are the delay before sedimentation starts, the rate of sedimentation in the steady state, and the radius of the sedimenting aggregate. The radius can be calculated from the rate of fall of the aggregates and agrees well with the microscopically observed radius. It is inversely proportional to the hematocrit, which explains the elevated sedimentation rates in anemia.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Erythrocyte aggregation in clinical medicine.

Red cell aggregation is one of the part of the properties of blood which determine blood flow in the impaired microcirculation. Erythrocyte aggregation does influence not only the viscosity at low rates of shear but leads to a vicious circle which again impairs the blood flow in the microcirculation. In the other hand it seems obvious that red cell aggregation leads to an inhomogenous distribution of microcirculatory blood flow (maldistribution) thereby decreasing the oxygen transport tissue. In a great number of diseases red cell aggregation is increased and in some diseases this fact is responsible for clinical symptoms. This view is supported by the therapeutic benefit seen in patients with paraproteinaemia as well as in patients with vascular diseases treated with plasmapheresis or defibrinogenation, respectively. There is no doubt about, a reduction of red cell aggregation by desaggregating drugs to improve microcirculatory blood flow and do increase the oxygen supply to tissue. It is however hard to differentiate between the influence of red cell aggregation and/or plasma viscosity on the impaired microcirculation since both parameters are closely connected in most of these diseases.

Blood Viscosity↗

Effect of immunoglobulins and IgG-fragments on the human erythrocyte aggregation, studied by a rheoscope combined with image analyzer.

Using a rheoscope, combined with a TV image analyzer and a computer, the effects of immunoglobulins and IgG-fragments on the process of human erythrocyte aggregation were determined. The immunoglobulins accelerated the aggregation; the effect increased with their molecular weight, i.e., IgG congruent to gamma-globulin less than IgA less than IgM. An empirical relationship, expressing the dependence on the immunoglobulin concentrations, was proposed. F(ab')2-fragment accelerated the aggregation, more effectively than IgG, while Fab- and Fc-fragments did not. Therefore, two Fab-portions are presumably needed to form the aggregates, and the flexibility between two Fab-portions may be important. A case of multiple myeloma showed an increased aggregation, due to the increased myeloma protein.

Erythrocyte Aggregation↗

Whole blood viscosity, plasma viscosity and erythrocyte aggregation in nine mammalian species: reference values and comparison of data.

In this study species-specific values for whole blood viscosity (WBV), plasma viscosity (PV) and erythrocyte aggregation (EA) were determined in a total of 360 animals. We used 40 individual adult animals of nine mammalian species: horse, pig, dog, cat, rat, cattle, sheep, rabbit and mouse. WBV measurements were carried out using a LS30 viscometer, PV was measured using OCR-D and EA was measured using a Myrenne aggregometer and the LS30 (aggregation index at low shear rate). At low shear rates (0.7 s(-1) and 2.4 s(-1)) haematocrit (Hct)-standardized (40 % Hct) samples showed a higher value of WBV and EA in horse, pig, dog and cat. In cattle, sheep, rabbit and mouse, EA and WBV were markedly decreased and EA was almost undetectable, although the plasma fibrinogen concentration was higher in these animals. Rats showed the highest WBV at low shear rate in native blood and WBV was not different from horse in Hct-standardized blood; however, EA was very low in the rat, a result that might be explained by mechanical or geometrical properties of the red blood cell. EA correlated with the plasma protein concentration in each species except dog and mouse. In horse, cattle and pig, EA correlated with the plasma fibrinogen concentration. At high shear rate (94 s(-1)), WBV was higher in cattle than cat and rat, and dog had higher values than horse, suggesting specific interspecies differences depending on low shear and high shear values of WBV, as a result of mechanisms that influence RBC flexibility. PV was highest in cattle and lowest in rabbit and mouse and did not correlate with WBV. Haemorheological parameters differed between the species. Each species has its own rheological fingerprint. The physiological significance of these variations among mammalian species has not yet been established. Viscosity contributes to endothelial cell shear stress. While haemorheological parameters differ across the species it may be postulated that factors influencing flow-mediated endothelial cell signal transduction are different among the species.

Animals↗

Inhibition and acceleration of erythrocyte aggregation induced by small macromolecules.

The aggregation (especially the 'rouleau' formation) of human erythrocytes induced by polysaccharide and polyglutamic acid was quantitatively examined by using a low-shear rheoscope combined with a television image analyzer and a computer. (1) The morphological characteristics of rouleaux induced by these macromolecules are presented. (2) Polysaccharides with high molecular weights of 70 400 and 494 000 and poly(glutamic acids) with weights of 50 000 and 66 000 formed the rouleaux (then the three-dimensional aggregates). But polysaccharides with the low molecular weights of 10 300 and 42 500 and poly(glutamic acids) with weights of 8000 and 20 000 did not. The dependences of the velocity of rouleau formation on the macromolecule concentration and on the shear rate are shown. (3) The erythrocyte aggregation induced by high-molecular-weight polysaccharides was inhibited by low-molecular-weight polysaccharides and glucose, but was not affected by low-molecular-weight poly(glutamic acids). (4) The aggregation induced by high-molecular-weight poly(glutamic acids) was inhibited by poly(glutamic acid) with a molecular weight of 8000, but was accelerated by that of 20 000. The poly(glutamic acid)-induced aggregation was not affected by low-molecular-weight polysaccharides. (5) The stereochemical structure-dependent interaction (or the mode of bridging) of macromolecules with erythrocytes was stressed for the mechanism of erythrocyte aggregation.

Adult↗

Inflammation-sensitive proteins and erythrocyte aggregation in atherothrombosis.

OBJECTIVE: To find the relative contribution of various inflammation-sensitive proteins including fibrinogen, immunoglobulins (IgG, IgM and IgA), ceruloplasmin and high sensitivity C-reactive protein (hs-CRP) to the induction and/or maintenance of enhanced erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors. METHODS: The degree of erythrocyte adhesiveness/aggregation was determined by a simple slide test and image analysis. In addition, we measured various inflammation-sensitive protein levels including fibrinogen, ceruloplasmin, immunoglobulins and hs-CRP in a group of 234 individuals with atherothrombotic risk factors and healthy ones. Pearson partial correlations and multiple linear regression analysis were performed. RESULTS: Fibrinogen was found to be the major protein contributing to the enhanced erythrocyte adhesiveness/aggregation, explaining 30% of the model. Fibrinogen and IgG together explained 32.4% of the model. Other inflammation-sensitive proteins did not reach statistical significance and were excluded from the model. CONCLUSIONS: Among inflammation-sensitive proteins measured in our cohort, fibrinogen is the dominant contributor to erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors and healthy ones. These findings may pave the way for the development of therapeutic strategies directed at the attenuation of erythrocyte aggregability in individuals with atherothrombosis.

Aged↗

Erythrocyte aggregate rheology by transmitted and reflected light.

Both the transmission of light through a confined layer of blood and the reflection from the surface of that layer have been utilized for studying the rheology of erythrocyte aggregates. The two methods do not necessarily provide the same information. The light reflected from the blood layer relates to the rheological behavior of erythrocytes near the blood surface, whereas the light transmitted relates more to the properties of blood in bulk. This investigation makes direct comparison between the transmitted and reflected light methods with regard to the kinetics of aggregation in thin and thick layers of blood as well as following shear flow excitation steps of different sizes. Also, the transmission and reflection for static blood layers of varying thicknesses were determined. The kinetics of aggregation from transmitted and reflected light measurements are compared both graphically and by equations containing multiple characteristic aggregation times. The number of characteristic times required for accurate description increases with the time over which the aggregation process is monitored. The first 40 seconds of the aggregation process are precisely described by two characteristic times. For normal blood the characteristic times from reflection measurements are shorter than those from transmission measurements.

Erythrocyte Aggregation↗

[Erythrocyte aggregation and clinical course stages of venous insufficiency of the legs].

A double vicious circle at the venule and capillary level had already been pointed out by J. Dormandy and G. Nash as a pathophysiologic mechanism of rheological disorders associated with venous insufficiency of the lower limbs. Afterwards, such disorders were found by many authors when ex vivo analysis were performed on venous insufficient patients. However the time of their onset and their evolution in the course of the disease remain unknown. We studied red cell aggregation and plasma fibrinogen in 67 patients depending on the evolutive stage: 1st stage: isolated functional disorders, 2nd stage: trunk varicose vein linked to ostial incompetence, 3rd stage: trunk varicose vein linked to ostial incompetence with chronic trophic skin changes. The results showed that red cell aggregation and fibrinogen values are increased with the severity of the diseases. The rheological parameters increase when compared to controls from the first stage. Within the studied population, we avoided skewed results due to age and fibrinogen level by covariance analysis. Therefore recorded differences were practically linked with erythrocyte aggregability. Thus, red cell aggregation appears to be both an aggravating factor and a severity marker of the disease, proving the relevance of a rheological treatment in the lower limb insufficiency.

Adult↗

[Effect of fructose-1,6-diphosphate and trental on the erythrocyte aggregating capacity in ischemic heart disease].

It was shown that fructose-1.6-diphosphate was capable of marked suppression of the aggregation power of the blood erythrocytes of patients with acute myocardial infarction and angina of effort. The antiaggregation effect of the drug was dose-related and enhanced with an increase in the time of its contact with erythrocytes. The antiaggregation effect of pentoxifylline was not of distinct dose-related nature. Its antiaggregation power did not considerably depend on the time of incubation with erythrocytes.

Adult↗