Which sub-compartments of fat mass and fat-free mass are related to blood viscosity factors?

The size of body compartments is a determinant of several factors of blood viscosity. Red cell aggregation is proportional to fat mass while hematocrit is proportional to both fat-free mass and abdominal adiposity, but which parts of these body components are involved in this relationship is not known. Segmental bioelectrical impedance analysis (sBIA) provides a possibility to delineate the relationships more precisely between various subdivisions of the body and blood viscosity factors, going farther than preceding studies using non segmental BIA. In this study we investigated in 38 subjects undergoing a standardized breakfast test with mathematical modelling of glucose homeostasis and a segmental bioelectrical impedance analysis (sBIA) the relationships between the various compartments of the body and viscosity factors. Blood and plasma viscosity were measured with the Anton Paar rheometer and analyzed with Quemada's model. The parameters better correlated to hematocrit are fat free mass (r = 0.562) and its two components muscle mass (r = 0.516) and non-muscular fat-free mass (r = 0.452), and also trunk fat mass (r = 0.383) and waist-to hip ratio (r = 0.394). Red cell aggregation measurements were correlated with both truncal and appendicular fat mass (r ranging between 0.603 and 0.728). Weaker correlations of M and M1 are found with waist circumference and hip circumference. This study shows that the correlation between lean mass and hematocrit involves both muscle and non-muscle moieties of lean mass, and that both central and appendicular fat are determinants of red cell aggregation.

Investigating the blood rheology in the first trimester pregnancies with high risk for preeclampsia.

BACKGROUND: Pregnancy is a dynamic process associated with changes in vascular and rheological resistance. Maternal maladaptation to these changes is the leading cause of pregnancy complications such as preeclampsia. OBJECTIVE: This study aimed to assess the hemorheological alterations in pregnancies with a high risk for preeclampsia in the first trimester. METHODS: Ninety-two pregnant women were allocated into the high preeclampsia risk group (37 cases) and control groups (55 cases). Plasma and whole blood viscosity and red blood cell morphodynamic properties, including deformability and aggregation were assessed by Brookfield viscometer and laser-assisted optical rotational cell analyzer (LORRCA) at 11-14 gestational weeks. RESULTS: Whole blood viscosity was significantly higher in the high-risk group at all shear rates. Plasma viscosity and hematologic factors showed no differences between the groups. Hematocrit levels positively correlated with high blood viscosity only in the high-risk group. There were no significant changes in the other deformability and aggregation parameters. CONCLUSIONS: Changes in the whole blood viscosity of pregnant women with high preeclampsia risk refer to impaired microcirculation beginning from the early weeks of gestation. We suggest that the whole blood viscosity is consistent with the preeclampsia risk assessment in the first trimester, and its measurement might be promising for identifying high-preeclampsia-risk pregnancies.

Experience with pre-diluted plasma exchange therapy for hyperviscosity syndrome.

INTRODUCTION: Plasma exchange therapy (PE) is useful for patients with primary macroglobulinemia and multiple myeloma who present with hyperviscosity syndrome. However, hyperviscous blood may coagulate in the circuit during treatment, and in that case necessitate discontinuation of the treatment. This time, we report that we were able to prevent coagulation in the circuit by adding some ideas during the membrane separation method. METHODS: Physiological saline is injected in front of the plasma separation membrane to pre-dilute the blood, followed by filtration through the plasma separation membrane. RESULTS: As a result of pre-diluting with physiological saline to reduce the viscosity entering the separation membrane, it was possible to process the planned target amount. CONCLUSION: In patients with hyperviscosity syndrome who showed intracircuit coagulation during plasma exchange therapy, devising a predilution method should be considered as one of the ways to continue treatment.

Phenomenological characterization of blood's intermediate shear rate: a new concept for hemorheology.

The phenomena of aggregation, breakdown, and disaggregation of the rouleaux of red blood cells (RBCs) in addition to deformability affect the human blood viscosity at different shear rates. In this study, the intermediate shear rate is introduced and defined when the effect of aggregation on the change of blood viscosity is diminished; and afterwards, the alteration in the blood viscosity is dominantly affected by the deformation of RBCs. With this respect, modeling the effective parameters on the blood shear-thinning behavior including hematocrit and plasma viscosity was performed for the two different shear regions discriminated by the proposed intermediate shear rates. The presented rheological model reflects a phenomenological approach to assess the human blood viscosity with an average error of ± 5% compared to experimental data for hematocrits between 0.299 and 0.702, subjected to various shear rates from 0.2 to 680 1/s. The temperature changes as well as biochemical effects on whole blood viscosity are characterized by the introduced plasma viscosity-dependent model. The presented comprehensive model could be used for better understanding of blood flow hemodynamics and analyzing the shear dependence of aggregation and deformability behaviors of RBCs.

Study of Non-Newtonian blood flow - heat transfer characteristics in the human coronary system with an external magnetic field.

This paper proposes a novel mathematical model of non-Newtonian blood flow and heat transfer in the human coronary system with an external magnetic field. As the blood viscosity is assumed to depend not only on shear rate but also on temperature and magnet strength, the modified Carreau-Yasuda viscosity model is formulated. The computational domain includes the base of the aorta, the right coronary artery, and the left coronary artery, with the left circumflex and left anterior descending arteries. The element-based finite volume method is derived for the solution of the proposed model. Numerical simulations are carried out to investigate the magnetic field effect on the blood flow-heat transfer characteristic in the human coronary system. It is found that the magnetic field has a significant impact on fluid viscosity, leading to enhanced fluid velocity.

Hyperviscosity syndromes; hemorheology for physicians and the use of microfluidic devices.

PURPOSE OF REVIEW: Hyperviscosity syndromes can lead to significant morbidity and mortality. Existing methods to measure microcirculatory rheology are not readily available and limited in relevance and accuracy at this level. In this review, we review selected hyperviscosity syndromes and the advancement of their knowledge using microfluidic platforms. RECENT FINDINGS: Viscosity changes drastically at the microvascular level as the physical properties of the cells themselves become the major determinants of resistance to blood flow. Current, outdated viscosity measurements only quantify whole blood or serum. Changes in blood composition, cell number, or the physical properties themselves lead to increased blood viscosity. Given the significant morbidity and mortality from hyperviscosity syndromes, new biophysical tools are needed and being developed to study microvascular biophysical and hemodynamic conditions at this microvascular level to help predict those at risk and guide therapeutic treatment. SUMMARY: The use of 'lab-on-a-chip' technology continues to rise to relevance with point of care, personalized testing and medicine as customizable microfluidic platforms enable independent control of many in vivo factors and are a powerful tool to study microcirculatory hemorheology.

Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19. OBJECTIVES: This study sought to determine the association between estimated BV (eBV) and mortality among hospitalized COVID-19 patients. METHODS: The study population included 5,621 hospitalized COVID-19 patients at the Mount Sinai Health System from February 27, 2020, to November 27, 2021. eBV was calculated using the Walburn-Schneck model. Multivariate Cox proportional hazards models were used to evaluate the association between eBV and mortality. Considered covariates included age, sex, race, cardiovascular and metabolic comorbidities, in-house pharmacotherapy, and baseline inflammatory biomarkers. RESULTS: Estimated high-shear BV (eHSBV) and estimated low-shear BV were associated with increased in-hospital mortality. One-centipoise increases in eHSBV and estimated low-shear BV were associated with a 36.0% and 7.0% increase in death, respectively (P < 0.001). Compared with participants in the lowest quartile of eHSBV, those in the highest quartile of eHSBV had higher mortality (adjusted HR: 1.53; 95% CI: 1.27-1.84). The association was consistent among multiple subgroups, notably among patients without any comorbidities (adjusted HR: 1.69; 95% CI: 1.28-2.22). CONCLUSIONS: Among hospitalized COVID-19 patients, increased eBV is significantly associated with higher mortality. This suggests that eBV can prognosticate patient outcomes in earlier stages of COVID-19, and that future therapeutics aimed at reducing WBV should be evaluated.

Hemorheological and microvascular disturbances in patients with type 2 diabetes mellitus.

BACKGROUND: In the blood vessels the impaired hemorheological parameters in patients with type 2 diabetes mellitus (T2DM) could lead to elevated flow resistance, increased forces at the endothelial wall and to microvascular disturbances. OBJECTIVE: The aim of the study is to investigate the hemorheological variables and the changes of the skin blood flow responses to cold stress in T2DM patients. METHODS: The basic hemorheological parameters: hematocrit (Ht), fibrinogen (Fib), whole blood viscosity (WBV) and plasma viscosity (PV) were examined in 20 patients with T2DM and a control group of 10 healthy age and sex matched controls. The mechanisms of vascular tone regulation were investigated using the wavelet analysis of the skin temperature oscillations (WAST). The degrees of the microvascular tone changes were determined during a cold test in the endothelial (0.02-0.0095 Hz), neurogenic (0.05- 0.02 Hz) and myogenic (0.05- 0.14 Hz) frequency ranges. RESULTS: Significant increase of Fib and WBV in the patients in comparison to controls was found. The mean values of the amplitudes of the skin temperature (ST) pulsations decreased significantly during the cold stress only in the endothelial frequency range for the diabetic patients. CONCLUSIONS: The results of our study reveal parallel impairment of the blood rheological parameters and the cutaneous microcirculation in T2DM patients.

Sex-differential downregulation of methotrexate on plasma viscosity and whole blood viscosity in psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk for cardiovascular disease (CVD). Methotrexate (MTX) is often used as a first-line system therapy and there is a need to determine its effect on whole blood viscosity (WBV) and plasma viscosity (PV) in psoriasis.METHODSA prospective, single-center, interventional study with a total of 111 psoriatic patients who received MTX therapy from October 22, 2018, to December 28, 2019, and 111 age- and sex-matched healthy controls. Changes in WBV, PV, blood counts, liver and renal function were evaluated.RESULTSPsoriatic patients had significantly higher levels of WBV and relative viscosity (RV) at low shear rate (LSR), erythrocyte aggregation index (EAI), and PV than sex and age-matched healthy controls. PV was positively correlated with erythrocyte sedimentation rate (ESR), ESR was positively correlated with high sensitive C-reactive protein (hCRP). But only hCRP was positively associated with psoriasis area severity index (PASI) score. MTX significantly decreased the levels of PV, ESR, hCRP, and blood pressure (BP) in male patients, and the level of WBV in female patients. CONCLUSION: Sex-specific downregulation of MTX on WBV, PV, hCRP, and BP, indicating that the effect of MTX on the risk of cardiovascular disease was related with sex.

Biosensing of Haemorheological Properties Using Microblood Flow Manipulation and Quantification.

The biomechanical properties of blood have been used to detect haematological diseases and disorders. The simultaneous measurement of multiple haemorheological properties has been considered an important aspect for separating the individual contributions of red blood cells (RBCs) and plasma. In this study, three haemorheological properties (viscosity, time constant, and RBC aggregation) were obtained by analysing blood flow, which was set to a square-wave profile (steady and transient flow). Based on a simplified differential equation derived using a discrete circuit model, the time constant for viscoelasticity was obtained by solving the governing equation rather than using the curve-fitting technique. The time constant (λ) varies linearly with respect to the interface in the coflowing channel (ß). Two parameters (i.e., average value: <λ>, linear slope: dλdß) were newly suggested to effectively represent linearly varying time constant. <λ> exhibited more consistent results than dλdß. To detect variations in the haematocrit in blood, we observed that the blood viscosity (i.e., steady flow) is better than the time constant (i.e., transient flow). The blood viscosity and time constant exhibited significant differences for the hardened RBCs. The present method was then successfully employed to detect continuously varying haematocrit resulting from RBC sedimentation in a driving syringe. The present method can consistently detect variations in blood in terms of the three haemorheological properties.

Erythrocyte morphological symmetry analysis to detect sublethal trauma in shear flow.

The viscoelastic properties of red blood cells (RBC) facilitate flexible shape change in response to extrinsic forces. Their viscoelasticity is intrinsically linked to physical properties of the cytosol, cytoskeleton, and membrane-all of which are highly sensitive to supraphysiological shear exposure. Given the need to minimise blood trauma within artificial organs, we observed RBC in supraphysiological shear through direct visualisation to gain understanding of processes leading to blood damage. Using a custom-built counter-rotating shear generator fit to a microscope, healthy red blood cells (RBC) were directly visualised during exposure to different levels of shear (10-60 Pa). To investigate RBC morphology in shear flow, we developed an image analysis method to quantify (a)symmetry of deforming ellipsoidal cells-following RBC identification and centroid detection, cell radius was determined for each angle around the circumference of the cell, and the resultant bimodal distribution (and thus RBC) was symmetrically compared. While traditional indices of RBC deformability (elongation index) remained unaltered in all shear conditions, following ~100 s of exposure to 60 Pa, the frequency of asymmetrical ellipses and RBC fragments/extracellular vesicles significantly increased. These findings indicate RBC structure is sensitive to shear history, where asymmetrical morphology may indicate sublethal blood damage in real-time shear flow.

Blood rheometer based on microflow manipulation of continuous blood flows using push-and-back mechanism.

To understand the contributions of rheological properties to microcirculation, the simultaneous measurement of multiple rheological properties under continuous blood flows has been emphasized. However, existing methods exhibit limitations in terms of continuous and simultaneous monitoring. In this study, a simple method is suggested for simultaneously measuring four rheological properties (i.e., red blood cell (RBC) aggregation, blood viscosity, blood junction pressure, and RBC sedimentation) under a continuous blood flow. Using the push-and-back mechanism, which comprises a co-flowing channel, a test chamber, and an air compliance unit (ACU), blood is supplied to the test chamber and restored into the co-flowing channel periodically and reversely. First, RBC aggregation is quantified based on the intensity of the blood image in the test chamber. Second, blood viscosity and blood junction pressure are determined by analyzing the interface in the co-flowing channel. Lastly, RBC sedimentation is evaluated by analyzing the intensity of the blood image in the blood chamber. Based on quantitative studies involving several vital factors, the tubing length of ACU is set to L = 30 mm. The reference fluid (glycerin [20%]) is controlled in a periodic on-off manner (period = 240 s, and flow rate = 1 mL h-1). The blood flow rate is maintained at 1 mL h-1. Subsequently, the present method is used to determine the rheological properties of several blood samples with different hematocrits or diluents. Compared with previous studies, the present method yields sufficiently consistent trends with respect to the hematocrit level or concentration of dextran solution. The experimental results imply that the present method enables simultaneous and consistent measurements of four rheological properties of blood under continuous blood flows. This method can be regarded as a promising method for monitoring multiple rheological properties of blood circulating under an in vitro closed fluidic circuit.

Animal blood in translational research: How to adjust animal blood viscosity to the human standard.

Animal blood is used in mock circulations or in forensic bloodstain pattern analysis. Blood viscosity is important in these settings as it determines the driving pressure through biomedical devices and the shape of the bloodstain. However, animal blood can never exactly mimic human blood due to erythrocyte properties differing among species. This results in the species-specific shear thinning behavior of blood suspensions, and it is therefore not enough to adjust the hematocrit of an animal blood sample to mimic the behavior of human blood over the entire range of shear rates that are present in the body. In order to optimize experiments that require animal blood, we need models to adapt the blood samples. We here offer mathematical models derived for each species using a multi linear regression approach to describe the influence of shear rate, hematocrit, and temperature on blood viscosity. Results show that pig blood cannot be recommended for experiments at low flow conditions (<200 s-1 ) even though erythrocyte properties are similar in pigs and humans. However, pig blood mimics human blood excellently at high flow condition. Horse blood is unsuitable as experimental model in this regard. For several studied conditions, sheep blood was the closest match to human blood viscosity among the tested species.

Energy loss associated with in-vitro modeling of mitral annular calcification.

INTRODUCTION: Study aims were to compare hemodynamics and viscous energy dissipation (VED) in 3D printed mitral valves-one replicating a normal valve and the other a valve with severe mitral annular calcification (MAC). Patients with severe MAC develop transmitral gradients, without the commissural fusion typifying rheumatic mitral stenosis (MS), and may have symptoms similar to classical MS. A proposed mechanism relates to VED due to disturbed blood flow through the diseased valve into the ventricle. METHODS: A silicone model of a normal mitral valve (MV) was created using a transesophageal echocardiography dataset. 3D printed calcium phantoms were incorporated into a second valve model to replicate severe MAC. The synthetic MVs were tested in a left heart duplicator under rest and exercise conditions. Fine particles were suspended in a water/glycerol blood analogue for particle image velocimetry calculation of VED. RESULTS: Catheter mean transmitral gradients were slightly higher in the MAC valve compared to the normal MV, both at rest (3.2 vs. 1.3 mm Hg) and with exercise (5.9 vs. 5.0 mm Hg); Doppler gradients were 2.7 vs. 2.1 mm Hg at rest and 9.9 vs 8.2 mm Hg with exercise. VED was similar between the two valves at rest. During exercise, VED increased to a greater extent for the MAC valve (240%) versus the normal valve (127%). CONCLUSION: MAC MS is associated with slightly increased transmitral gradients but markedly increased VED during exercise. These energy losses may contribute to the exercise intolerance and exertional dyspnea present in MAC patients.

Association of blood viscosity with first-pass reperfusion in mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: Elevated blood viscosity has been reported as a risk factor for cerebrovascular disease. OBJECTIVE: The relationship between blood viscosity and outcomes of mechanical thrombectomy (MT) for large artery occlusion (LAO) were investigated in the present study. METHODS: A total of 238 patients were enrolled and systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) were measured using the scanning capillary tube viscometer. Receiver operating characteristic (ROC) analysis was performed to specify the association of viscosity with the first-pass reperfusion (FPR). Multivariable and regression analyses were performed to evaluate the relationship of viscosity with FPR and various variables. RESULTS: Based on ROC analysis, the best DBV cutoff value was 10.55 (cP). In multivariable analysis, high DBV was associated with FPR failure (odds ratio 2.82, 95% confidence interval 1.64-4.22; p = 0.001). Increased DVB could be associated with elevated SBV, hematocrit level, and blood urea nitrogen/creatinine ratio (p = <0.001, 0.004, and 0.002, respectively). CONCLUSIONS: Elevated DBV was associated with FPR failure. Patients with high DBV had longer thrombus length and required more stent passages than patients with low DBV.

Hemodialysis efficiency management from the viewpoint of blood removal pressure.

Degradation of dialysis efficiency during hemodialysis, caused by incompatible indwelling needle size or increase in hematocrit, is a serious problem that can threaten a patient's life. This study aims to derive a quantitative index for determining the indwelling needle diameter that can maintain an appropriate blood flow rate, and presents an effective method to prevent a decrease in the actual blood flow rate. The relationships between the set flow rate and various parameters such as indwelling needle diameter, blood viscosity, and arterial line pressure are analyzed. A simple and reliable method for estimating the actual blood flow rate is derived from these relationships. A correlation between viscosity and actual blood flow rate is estimated adequately by regression analysis using a least-squares method. The relationship between Reynolds number and the flow rate reduction ratio is also evaluated. A new parameter (simple estimation method for actual blood flow) is derived by measuring the blood removal pressure. A pump control approach that uses blood removal pressure is suggested, which can be a future research direction in the field of hemodialysis.

Simulation of Blood as Fluid: A Review From Rheological Aspects.

Blood flow in the human vascular system is a complex to understand example of fluid dynamics in a closed conduit. Any irregularities in the hemodynamics may lead to lethal cardiovascular disease like heart attack, heart failure and ischemia. Numerical simulation of hemodynamics in the blood vessel can facilitate a thorough understanding of blood flow and its interaction with the adjacent vessel wall. A good simulation approach for blood flow can be helpful in early prediction and diagnosis of the mentioned disease. The simulation outcomes may also provide decision support for surgical planning and medical implants. This study reports an extensive review of various approaches adopted to analyze the influence of blood rheological characteristics in a different class of blood vessels. In particular, emphasis was given on the identification of best possible rheological model to effectively solve the hemodynamics inside different blood vessels. The performance capability of different rheological models was discussed for different classes and conditions of vessels and the best/poor performing models are listed out. The Carreau, Casson and generalized power-law models were appeared to be superior for solving the blood flow at all shear rates. In contrast, power law, Walburn-Scheck and Herchel-Bulkley model lacks behind in the purpose.

COVID-19 Associated Hypercoagulability: Manifestations, Mechanisms, and Management.

ABSTRACT: Patients with severe coronavirus disease-2019 (COVID-19) frequently have hypercoagulability caused by the immune response to the severe acute respiratory syndrome coronavirus-2 infection. The pathophysiology of COVID-19 associated hypercoagulability is not fully understood, but characteristic changes include: increased fibrinogen concentration, increased Factor VIII activity, increased circulating von Willebrand factor, and exhausted fibrinolysis. Anticoagulant therapy improves outcomes in mechanically ventilated patients with COVID-19 and viscoelastic coagulation testing offers an opportunity to tailor anticoagulant therapy based on an individual patient's coagulation status. In this narrative review, we summarize clinical manifestations of COVID-19, mechanisms, monitoring considerations, and anticoagulant therapy. We also review unique considerations for COVID-19 patients who are on extracorporeal membrane oxygenation.

An Algorithm for the Noninvasive and Personalized Measurement of Microvascular Blood Viscosity Using Physiological Parameters.

Blood viscosity is one of the important parameters to characterize hemorheological properties of the human body. Its real-time and dynamic measurement has important physiological significance for studying the development and prevention of chronic diseases. This study researched noninvasive and personalized measurement of microvascular blood viscosity. In the microcirculation capillary network blood flow model, combined with pulse wave parameters, multiple regression analysis was used to fit the simulated radius of personalized physiological blood vessels to calculate the microvascular blood viscosity. The fitted value related to the simulated radius of the physiological blood vessel had a high correlation with the corresponding theoretically derived value (correlation coefficient: 0.904, P ≤ 0.001). The calculated value of the microvascular blood viscosity had a certain correlation with the clinical whole blood viscosity at a low shear rate (correlation coefficient: 0.443, P < 0.05). This algorithm could provide effective means for noninvasive and long-term individual monitoring and family health care.

Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests?

Hemostasis is a complex process in which abnormalities can cause shifts toward prothrombotic or prohemorrhagic states resulting in thrombosis or bleeding, respectively. Several coagulation tests may be required to characterize these defects but may yet not always reflect a patient's true hemostatic capacity. Thus, global coagulation tests aiming to simulate the coagulation process in vitro instead of measuring single components thereof are certainly of interest to assess prothrombotic or prohemorrhagic tendencies. This review describes the development and application of global coagulation tests, concentrating on the more widely used methods of viscoelastometry and thrombin generation. A focus is placed on conditions characterized by simultaneous changes of various components of hemostasis, such as anticoagulant therapy or hormone-induced coagulopathy, in which global coagulation tests are especially promising. If the key challenges of standardization and automation of these tests are solved, as is the case with automated thrombogram or clot waveform analysis, global coagulation assays will play an important role in the future of laboratory diagnostics of hemostasis and thrombosis.