Gender difference in rheologic properties of blood and risk of cardiovascular diseases

According to official statistical data there is a significant difference between pre-menopausal women and age-matched men in morbidity and mortality from cardiac diseases and especially from myocardial infarction. There are several speculations regarding the nature of this phenomenon which have both supporting and refuting evidence. Our hypothesis was that due to regular physiologic bleeding, rheological properties of blood of pre-menopausal women are superior to those of men, and place such women at a lower risk of cardiovascular diseases than men in any age group. We believe that this difference in hemorheological properties is due to the reduced concentration of red blood cells (RBCs) and due to greater population of younger and less population of older RBCs in female blood. We studied mechanical properties of blood from 47 pre-menopausal women and 50 age-matched men. Compared to female blood, male blood had higher viscosity and RBC aggregation and lower RBC deformability. Oxygen Delivery Index, calculated as a ratio of hematocrit to blood viscosity, was found to be significantly lower in male blood. Decreased oxygen delivery along with increased RBC aggregation and decreased RBC deformability may contribute to the higher risk for the development of cardiovascular diseases. Regular blood donation may reduce hematocrit and blood viscosity, improve rheological properties of blood, and increase oxygen delivery in men.     

Increased red blood cell deformability due to isoxsuprine administration decreases platelet adherence in a perfusion chamber: a double-blind cross-over study in patients with intermittent claudication

Platelet transport towards the vessel wall is influenced by the hematocrit, red blood cell (RBC) size, and shape. Recent in vitro studies have indicated that RBC deformability may also influence platelet transport. The observation that isoxsuprine, a known vasodilating drug, caused increased RBC deformability in vitro and decreased platelet transport in vitro prompted us to study the effects of this drug in vivo. The study was performed in a double-blind cross- over study of isoxsuprine v placebo in ten patients with peripheral arterial insufficiency. RBC deformability was estimated from viscosity measurements using the blood viscosity equation of Dintenfass and expressed as T value. Platelet transport was studied in an annular perfusion chamber according to Baumgartner. Human umbilical arteries were used as blood vessels. Perfusion studies were performed with whole blood or with RBCs of the patients mixed with normal platelets and plasma at a standardized hematocrit and platelet count. An increase in RBC deformability concomitant with a decrease in platelet adherence was observed in patients on isoxsuprine with a drop in T value of approximately 0.06 (from 0.91 toward 0.86), and a concomitant decrease in platelet adherence of 20% to 40%. These observations differed significantly from the results in the placebo group and showed a significant group-period interaction at the cross-over of medication (analysis of variance). The effects on platelet adherence were observed at high vessel wall shear rate (1,800 s-1) with perfusates consisting of patients' RBCs and donor plasma and platelets at standardized hematocrit and platelet count. No differences were observed under these conditions at a shear rate of 300 s-1. When whole blood of patients was used, nonsignificant effect was observed at shear rates of 300 s-1 and 1,800 s-1. This was probably caused by the added noise due to variations in hematocrit and platelet number. These data demonstrate that isoxsuprine increases RBC deformability, and they suggest the possibility of decreasing platelet-vessel wall interaction in vivo by manipulation of RBC deformability.     

Blood rheology and aging

The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals; this finding of increased fibrinogen concen-tration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.     

Relations between plasma-erythrocyte viscosity factors and ESR]

The ESR is usually put in relationship: to the real density of the RBCs (erythrocytes) (difference between the RBC specific gravity and the plasma one), and to the resistance that the RBCs meet moving in a medium, which is due to the plasma viscosity and to the total external RBC surface. When the RBCs take shape of aggregates, their external surface is decreased and ESR increases. The most important plasma factor causing changes in ESR is the fibrinogen level followed by the plasma globulins and by the products arising from the tissue damage. The resistance that the RBCs meet moving in the plasma is well expressed by the measurement of the plasma-RBC viscosity considering that is inclusive of both factors that are the plasma viscosity and the external RBC surface. The plasma-RBC viscosity is the resultant of several factors: Fa = Fb - Fe - Fs - Fm, were: Fa is the resultant, Fb the attracting forces due to the proteic macromolecules, Fe the repulsing forces due the negative charges. Fs the repulsing forces due to the shear-stress, Fm the force which opposes itself against the surface tension of the aggregation; it depends on the RBC morphology and on the RBC rigidity. The ESR has been recently used like an index of the RBC aggregation. The Authors study the relationship between several hemorheological parameters and the ESR in infective and inflammatory processes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased blood fluidity in progressive systemic scleroderma

The aim was to define blood rheology in progressive systemic scleroderma (PSS). 55 patients were compared to controls. Blood and plasma viscosity, hematocrit, red cell aggregation, and deformability were measured. Except for hematocrit, all these variables are significantly altered, indicating a loss of blood fluidity in PSS. Drugs had no obvious effect on blood rheology, but the clinical picture did. The loss of blood fluidity in PSS is suggested to play a pathophysiological role in the initiation of Raynaud phenomena, from which all patients suffered.     

Aggregability and disaggregability of erythrocytes in women suffering from ovarian cancer: evidence for an increased disaggregation threshold

In order to further characterize the alterations of erythrocyte aggregation described in ovarian cancer, we measured it with laser backscattering in eleven women suffering from ovarian cancer (mean age: 44.7 +/- 3.6, extreme values: 28-61 yr) compared with thirteen matched control women. Blood rheology exhibited a wide variability in cancer patients, with some unusually high values of plasma viscosity and/or RBC aggregation in individual cases. The only significant differences were found for the RBC disaggregation threshold which was higher in patients than in controls (78.06 +/- 10.14 vs 52.6 +/- 3.15 s(-1), p < 0.05), while hematocrit was lower (34.45 +/- 1.42 vs 38.23 +/- 0.75, p < 0.05). A negative correlation between hematocrit and corrected blood viscosity on the whole sample of subjects (r = 0.454, p < 0.05) indicates that hematocrit is decreased in subjects prone to high viscosity, resulting in similar values of apparent blood viscosity in controls and patients. Thus, a lower disaggregability of RBCs is evidenced in women with ovarian cancer, as well as a tendency to blood hyperviscosity compensated by a reduction of hematocrit which suggests that there may be some degree of 'viscoregulation'.     

Deformability and intrinsic material properties of neonatal red blood cells

Whole cell and membrane deformability are essential for red blood cell (RBC) survival and for effective blood flow. Neonatal RBCs display several specific properties (eg, large size, high hemoglobin F) that could influence their deformation characteristics and contribute to their shortened life span. The present study was designed to compare selected rheologic properties (cellular deformability, pressure required to aspirate RBC into micropipettes, static and dynamic viscoelastic material properties) of neonatal and adult RBCs. RBC deformability, as studied by a rheoscope, was similar for neonates and adults over a shear stress range of 2.5 to 500 dyn/cm2. The pressure required to aspirate RBCs completely into 3.3-micron diameter pipettes was 129 +/- 87 dyn/cm2 for neonatal RBCs and 71 +/- 37 dyn/cm2 for adult RBCs. The aspiration pressure for neonatal and adult RBCs increased with increasing RBC volume, suggesting that the increased mean aspiration pressure for neonatal RBCs resulted from their larger volume. When RBCs with same volume and diameter were compared, the aspiration pressure tended to be smaller for neonatal RBCs than for adult cells. To characterize material properties determining RBC deformability, we measured membrane extensional (shear) and bending elastic moduli, the time constant for elastic recovery from extensional deformation and hemoglobin viscosity (ie, cytoplasmic viscosity) of neonatal and adult RBCs. Membrane surface viscosity and time constant for recovery from bending deformation were calculated. The extensional and bending moduli of neonatal RBCs were slightly smaller (10% and 16%, respectively) compared with adult cells. This suggests that the static resistance of neonatal RBC membrane to deformation and failure in response to a given force is slightly smaller. The time constant for recovery from extensional deformation of neonatal RBCs was larger by 14%, compared with adult cells. The time constant for bending deformation related to the RBC diameter and surface area was increased by 18% in the neonates. Membrane surface viscosity and hemoglobin viscosity were similar for both cell types. These results indicate that the deformability and viscoelastic properties of neonatal RBCs deviate only slightly from those of adult RBCs and that the increased aspiration pressure of neonatal RBCs is solely due to their large size. Some of the specific deformation characteristics observed in this study (increased aspiration pressure, decreased resistance to elastic deformation) may contribute to the shortened life span of neonatal RBCs.     

The microrheological behavior of young and old red blood cells in athletes

Previous studies have shown a difference in rheological properties of young versus senescent RBCs. There are data that the athletes blood has more young RBCs than untrained people. Our research was a comparative study of the microrheological properties of young and old RBCs in athletes and in untrained people that was as control group. In athletes (men, n=24) and group of the control (men, n=20) the following parameters were measured: RBC aggregation (ARBC; Myrenne aggregometer) and deformability, RBC suspension and plasma viscosity as well as osmolarity, albumin, globulin and fibrinogen concentration, MCHC. Red cells were density (i.e., age) fractionated by the method of Murphy. After centrifugation the top 10% of the packed cell column (RBCtop, relatively young cells) and the bottom 10% (RBCbot, relatively old cells) were resuspended at 40.0+/-0.4% (in plasma) for aggregation, deformation and suspension viscosity measurements. It was found significant difference in aggregation and rigidity of the all RBC subpopulations between athletes and control group. The difference in aggregation was associated with reduced fibrinogen and increased ratio albumin/globulin in athletes. Besides, the correlation between aggregation RBCtop and RBCbot with fibrinogen was decreased in athletes. It was one of the cause of high fluidity of the RBCtop- and RBCbot suspensions and whole blood in athletes and more effective oxygen transport than in untrained people.     

Metabolic depletion decreases the aggregability of erythrocytes

We studied the influence of metabolic depletion on red blood cell (RBC) aggregability, which is a determinant of blood flow. Heparinized blood was stored at room temperature for 0, 24, and 48 h. RBCs were washed twice and resuspended in Tris-buffer containing 3% dextran 70 (hematocrit 30%). Suspension viscosities were measured at 37 °C and shear rates of 37.6 and 0.1 s(-1), RBC aggregability was analysed by the sedimentation rate, direct microscopic visualization and a Myrenne aggregometer. RBCs in autologous plasma showed an increasing echinocytic shape transformation, which was reversible in buffer. The viscosities of RBC suspensions in buffer remained unchanged at both low (0.1 s(-1)) and high shear rate (37.6 s(-1)), the latter result indicating an unchanged RBC deformability. RBC aggregability decreased: The RBC sedimentation rates were 40.7 ± 5.0, 29.3 ± 13.4, and 13.3 ± 11.2 mm/h (p < 0.001) at 0, 24, and 48 h, respectively, which correlated well with the visual aggregability index and the Myrenne aggregation parameters M and M1. We conclude that metabolic depletion for 48 h leads to RBC swelling and a reversible echinocytic shape transformation. These ATP-depleted, but normally shaped RBCs had a decreased aggregability. In contrast to all other methods used, low shear viscosity was inaccurate and should not be used to test RBC aggregability.     

Alteration of erythrocyte biophysical properties in patients with ischemic cerebrovascular disorders]

Several erythrocyte biophysical properties (erythrocyte deformability, erythrocyte aggregation and erythrocyte electrophoretic mobility) were investigated in patients with cerebral infarction and in individuals with risk factors of stroke (RFS population; RFSP). Blood viscosity, plasma viscosity, hematocrit, plasma fibrinogen level and yield shear stress (YSS) were also tested. In comparison with the results in a control group, erythrocyte deformability (erythrocyte length under a certain constant shear stress and erythrocyte filterability) was less in both the patient group and the group of RFSP and there is an accompanying increase of erythrocyte aggregation. Blood viscosity and fibrinogen level were higher in the patient groups. There was no correlation between erythrocyte deformability and other hemorheological parameters. Our results suggest that significant alteration of erythrocyte biophysical properties may be implicated in the pathogenesis of ischemic stroke. These abnormalities are associated with some of the risk factors of stroke such as hypertension, atherosclerosis and cardiovascular disorders.     

Artificial surface effect on red blood cells and platelets in laminar shear flow

Red blood cell (RBC) effects on platelet adhesion to a nonbiologic test surface (tetrafluoroethylene propylene copolymer) and platelet aggregation during laminar shear flow for shear rates to 5,680 s-1 (corresponding to shear stress to 200 dyne/cm2) were investigated. Results on hemoglobin (Hb) and adenosine diphosphate (ADP) release from RBCs, percent decrease of single platelets in the bulk, and percent of test surface covered with platelets were obtained in a cone-and-plate (CP) viscometer for samples of whole blood, suspensions of RBC ghosts in platelet-rich plasma (PRP), and suspensions of RBCs in either PRP or platelet-poor plasma. Results obtained over the shear rate range studied for samples of normal hematocrit indicated that low-stress shearing led to ADP and Hb release from intact RBCs; shear-induced release of ADP from RBCs was about twice that of platelets, and of the total ADP released, the ADP released from RBCs contributed about six times that of the platelets to single platelet reduction in the bulk and about twice that of the platelets to platelet adhesion, ie, coverage of the test surface with platelets. Results obtained for various hematocrits showed that above a threshold hematocrit of about 25% to 35% the RBCs (suspended in PRP) had a greater contribution to ADP release, platelet adhesion, and platelet aggregation than the platelets themselves. Single platelet reduction for samples of RBC ghosts suspended in PRP correlated with shear rate level and not with shear stress.     

Does haemorheology explain the paradox of hypoxemia during exercise in elite athletes or thoroughbred horses?

Exercise-induced arterial hypoxemia (EIAH), i.e., a significant drop of O2 arterial partial pressure during sea level exercise, has been shown in both aerobically trained athletes and athletic animal species. The mechanisms potentially involved include ventilation/perfusion inequality and/or pulmonary diffusing capacity limitation. In thoroughbred horses, EIAH is going with pulmonary haemorrhage (EIPH). Stress failure of pulmonary capillaries leading to diffusion limitation has been proposed. Indeed, during intense exercise, the increased cardiac output and blood viscosity combine to rise capillary wall stress. Blood rheology may participate to the increase of VA/Q mismatch and capillary wall stress. High level of hematocrit (Hct) are known to alter blood flow distribution and rise shear stress in pulmonary capillaries. Any change in red blood cells (RBC) deformability may lead to aggregation at low shear rate, in post capillary veinules. There are contrasting data regarding the effects of blood rheology on EIPH in horses, however the large augmentation of hematocrit during exercise may cause vessel wall stress. In humans, greatest increase in hematocrit may participate to EIAH as well as RBC deformability. Today there is no consensus opinion and further studies of blood rheology in athletes is a field of interest.     

Hemorheological parameters as determinants of myocardial tissue hematocrit values

It is well known that the hematocrit in microvessels with diameters smaller than 1000 microm is lower than either venous or arterial hematocrit, thereby resulting in significantly lower mean hematocrit values for vessels perfusing a given tissue (i.e., lower tissue hematocrit). The mechanisms that underlie this reduction of microvascular hematocrit include axial migration, plasma skimming and the Fahraeus Effect. It has been previously demonstrated in rats that a linear hematocrit gradient normally exists through the thickness of the left ventricular myocardium, and that this gradient is sensitive to alterations of the rheological properties of the circulating blood. The gradient is abolished if the RBC in the perfusate are rigid; fibrinogen infusions, and thus increases of both plasma viscosity and RBC aggregation, also affect this gradient. In a new series of studies, it has been observed that enhanced RBC aggregation affects the myocardial hematocrit gradient regardless of alterations of plasma viscosity. Although the exact mechanisms responsible for the myocardial hematocrit gradient, as well as its physiological significance, are not yet clearly known, it is possible to speculate that alterations in local hematocrit could adversely affect myocardial perfusion and function.     

Haemolysis and abnormal haemorheology in sickle cell anaemia

Although pulmonary hypertension, leg ulcers, priapism, stroke and glomerulopathy in sickle cell anaemia (SCA) result from the adverse effects of chronic haemolysis on vascular function (haemolytic phenotype), osteoneocrosis, acute chest syndrome and painful vaso‐occlusive crises are caused by abnormal vascular cell adhesion and increased blood viscosity (viscosity‐vaso‐occlusion phenotype). However, this model with two sub‐phenotypes does not take into account the haemorheological dimension. We tested the relationships between the biological parameters reflecting the haemolytic rate (haemolytic component) and red blood cell (RBC) rheological characteristics in 97 adults with SCA. No significant difference in the proportion of patients with low or high haemolytic component in the low and high blood viscosity groups was observed. The RBC elongation index (i.e. deformability) was negatively correlated with the haemolytic component. The RBC aggregates strength (i.e. RBC aggregates robustness) was negatively correlated with RBC elongation index. Sickle RBCs with high density had lower elongation index and higher aggregates strength. In conclusion, (i) the ‘haemolytic’ phenotype is characterized by decreased RBC deformability and increased RBC aggregates strength and (ii) the viscosity‐vaso‐occlusive phenotype is characterized by increased RBC deformability but not always by increased blood viscosity. α‐thalassaemia modulates the haemorheological properties but other factors seem to be involved.     

Effects of fibrinogen and alpha2-macroglobulin and their apheretic elimination on general blood rheology and rheological characteristics of red blood cell aggregates

Methods of therapeutic apheresis, such as plasma exchange or rheopheresis eliminate moderately aggregating macromolecules like fibrinogen, as well as strongly aggregating substances like alpha2-macroglobulin from blood. In order to examine the specific effect of eliminating alpha2-macroglobulin as a highly aggregating macromolecule, this study aimed to analyze the different rheological properties of: (i) moderately aggregating red blood cells (RBCs; inducible by fibrinogen); and (ii) strongly aggregating RBCs (inducible by alpha2-macroglobulin). In vitro, RBC aggregate geometry was determined in the presence of strong and moderate aggregation inducing macromolecules. In vivo, flow behavior of RBC aggregates was analyzed by intravital microscopy. Using network scanning, the number of perfused and non-perfused microvessels was determined. In vitro, the higher adhesive forces of strongly aggregating RBCs led to both a higher packing density of single RBCs within aggregates, expressed as a significantly reduced thickness of individual RBCs, and greater deformation, expressed as a significantly diminished offset between RBCs and an increased curvature of RBCs at the ends of the aggregates. In vivo rheoscopy showed that only high aggregating RBCs persisted in the precapillary bed and led to the absence of RBCs in up to 40% of nutritive capillaries. These novel findings are of importance regarding recent developments in clinical hemorheology, specifically the clinical use of hemapheretic therapies for diseases in which impaired microcirculation plays a role in either their development or progression, such as age-related macular degeneration and complications of diabetes mellitus. Our data support that procedures reducing the concentration of alpha2-macroglobulin in blood by extracorporeal elimination might provide a more efficient improvement of overall blood fluidity in microcirculatory beds.     

Rheological properties of fetal red cells with special reference to aggregability and disaggregability analyzed by light transmission and laser backscattering techniques

Blood viscosity factors and fetal erythrocyte aggregability were investigated with light transmission (Myrenne device) during a cross-sectional study of blood drawn in utero by cord venepunctures in 119 normal fetuses between 18 and 39 weeks gestation. There was a progressive increased blood viscosity at native hematocrit (p < 0.01) explained by a gradual increase in both hematocrit (from 33% to 40%, p < 0.05) and Dintenfass' 'Tk' RBC rigidity index (p < 0.05), while plasma viscosity remained constant at 1.18 +/- 0.01 mPa x s as well as the h/eta ratio (188.4 +/- 2.7 mPa(-1) x s(-1)). The RBC aggregation index 'M' remained almost equal to zero (mean value: 0.04 +/- 0.01) before 32 wk gestation and then increased (p < 0.05) until delivery. The upper physiological limit for this parameter before 32 wk (mean +/- 2 SD) is 0.18. The RBC aggregation index 'M1' remained constant during pregnancy at 2.98 +/- 0.26, i.e., the upper physiological limit for this parameter during the intrauterine life (mean +/- 2 SD) is 7.85. Both fibrinogen (r = 0.479, p < 0.05) and albumin (r = 0.494, p < 0.01) correlated with time so that the albumin/fibrinogen ratio remained stable. We then studied with the laser retrodiffusion technique the venous blood of 20 women (18-43 yr, 37-40 wk gestation) and the cord blood of their newborns at birth, comparing RBC aggregation of: mothers (M), maternal RBCs resuspended on newborn plasma (MF), newborn RBCs resuspended on maternal plasma (FM), and newborns (F). Aggregability is higher in M (RBC aggregation time M < MF < FM < F; p < 0.01); RBC aggregation index at 10 s M > MF > FM > F; p < 0.01), with in turn the symmetric inverse picture for the partial disaggregation threshold (M > MF = FM > F). Thus RBC disaggregability is higher in newborns, and suspensions on maternal and newborn plasma suggest that half of this difference in aggregability (and disaggregability) between fetal and adult blood results from plasma factors and another half from erythrocytes.     

The role of erythrocyte aggregation in the abnormal hemorheology of multiple myeloma patients

OBJECTIVES: The aim of this study is to clarify whether increased aggregation of red blood cells (RBCs) of multiple myeloma (MM) patients is caused by changes in plasma chemical composition or is associated with alterations in RBC properties and in addition, to suggest an approach to revert the enhanced aggregation in MM toward normal. MATERIALS AND METHODS: 40 blood samples of MM patients and suspensions of control RBCs in MM plasma were examined. In addition, RBC aggregation in MM blood was studied in the presence of dextrans with mean molecular weights of 9.6 and 40 kDa (D9.6 and D40). A method based on electrical and dielectric properties of cellular suspensions was used to study RBC aggregation. In this method, a lower aggregation index demonstrates a higher aggregability. RESULTS: The mean values of aggregation index for whole blood of healthy individuals, control cells in MM plasma and MM blood sample are 19.0, 7.2 and 3.2%, respectively. The kinetics of RBC aggregation slow down with the decrease in the fraction of MM plasma. No correlation was found between RBC aggregation and the immunoglobulin plasma level. Addition of D9.6 to MM blood reverts the enhanced aggregation toward normal. DISCUSSION: The findings that RBC aggregation changes in the following order: MM blood > normal RBCs in MM plasma > control blood sample, suggest that surface-active plasma molecules play a role in enhanced aggregation in MM. The surface concentration of these molecules and hence RBC aggregability is reduced in the presence of dextrans due to their competitive adsorption onto RBC membrane. Because the end-to-end distance of D40 is quite comparable with the Debye length, the effect of this particular dextran on RBC aggregation is negligible.     

The effect of simvastatin therapy on hemorheological profile in coronary heart desease (CHD) patients

This study was designed to examine changes of hemorheological parameters in patients with CHD and hypercholesterolaemia (wide range of plasma total cholesterol level from 5.6 to 9.8 mmol.l-1) subjected to lipid lowering therapy with statins (simvastatin, 10.0-20.0 mg/day, dosage was dependent on an initial level of total cholesterol). Twenty female subjects were enrolled in this research program. Both prior to and following drug treatment for eight weeks, hemorheological measurements included plasma viscosity, high and low shear whole blood viscosity, hematocrit, RBC aggregation and rigidity. Treatment with simvastatin significantly (p<0.05) reduced total cholesterol, total triglycerides and low-density lipoprotein cholesterol (LDL-C). However, the hemorheological effects of lipid lowering therapy differed markedly between macro- and microrheological groups of parameters: plasma and whole blood viscosity were not significantly changed whereas RBC aggregation and its rigidity were decreased significantly after statin treatment. These results thus suggest that the rheologic effect of lipid lowering therapy concerned mainly the microrheological parameters: red cell aggregation and deformability.     

Shear-dependent aggregation characteristics of red blood cells in a pressure-driven microfluidic channel

Though the aggregation of red blood cells (RBCs) is a major determinant of blood viscosity, there have not been any available techniques to measure the effect of RBC aggregation on blood viscosity over a range of shear rates. The microfluidic shearing technique with vibration has been applied to an aggregometer for measuring the dynamic aggregation characteristic of RBCs. In measuring backscattered light intensity I(t) and pressure p(t) over time, both aggregation and the stress-shear rate information can be determined simultaneously. The feasibility and accuracy of the new aggregation measurement technique has been demonstrated to correlate with blood viscosity for normal and heated blood. We found that RBC aggregability showed shear-dependent behavior, which can be correlated directly with shear-thinning blood viscosity. The present measurements of the dynamic aggregation characteristic over shear rate enable the interpretation of the shear-rate dependent blood viscosity, which is greatly affected by RBC aggregation.