Red Blood Cell Aggregation Research Articles

Effect of whole-body cryotherapy treatments on blood morphology and blood rheology: red blood cell deformability, red blood cell aggregation in healthy subjects.

assessment of the effect of a series of 20 whole-body cryotherapy sessions on the morphological and rheological indicators of blood in healthy people. The experimental group consisted of 15 women and 15 men who underwent a series of whole-body cryotherapy treatments. The control group consisted of 15 women and 15 men - without intervention. For the analysis of blood biochemical parameters, venous blood was collected twice: Study 1: on the day of the commencement of whole body cryotherapy / from the control group; and Study 2: after a series of 20 cryotherapy sessions / from the control group (4 weeks). After whole-body cryotherapy a statistically significant decrease in RBC, HGB, HCT, MCV, EI 0.30 and an increase in MCHC and EI 2.19-60.30 were observed in women, as well as a decrease in MCV, MCH, AI and an increase in PLT, EI 0.30-60.30, AMP, T1/2 in men. The use of whole-body cryotherapy causes changes in blood counts in various directions and has a positive effect on the rheological properties of blood in women and men - it increases the elongation index and reduces the aggregation index.

Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19

The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach. Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology. Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.

Flexible dual-functionalized hyaluronic acid hydrogel adhesives formed in situ for rapid hemostasis

Hydrogel adhesives integrating both rapid and strong adhesion to blooding tissues and biocompatibility are highly desired for fast hemostasis. Herein, a flexible hyaluronic acid hydrogel adhesive is fabricated via photocrosslinking of the solution originating from dopamine-conjugated maleic hyaluronic acid (DMHA) in situ. The introduction of acrylate groups with high substitutions into the hydrogel matrix endows the adhesive with rapid gelation and strong tissue adhesion properties through photopolymerization. Moreover, the high substitution of catechol groups with unoxidized state can not only induce red blood cell aggregation and platelets adhesion but also adhere to wound tissue to further enhance hemostasis. Based on its bio-adhesion and procoagulant activity, the DMHA hydrogel formed in situ reveals superior hemostatic performance in the rat liver injury model and noncompressible hemorrhage model, and rabbit femoral artery puncture model, compared to commercial products (gauze, absorbable gelatin sponge) and oxidized DMHA (SMHA) hydrogel. Besides, the hydrogel exhibited good adaptability, biodegradability, and superior cytocompatibility as well as negligible inflammation. This hydrogel adhesive is a promising biological adhesive for hemorrhage control.

Sex-related differences in endothelial function and blood viscosity in the elderly population.

Elderly represents a growing population and cardiovascular diseases (CVD) is one of the leading causes of mortality in this population. Sex differences are involved in CVD with middle-aged males being at higher risk than females. After menopause, females are no longer protected by hormones and the role of sex on cardiovascular parameters involved in CVD, such as endothelial function and blood viscosity, is still unclear. The purpose of this study was to investigate the effect of sex on endothelial function, blood viscosity and CVD in elderly. Clinical investigation and blood analyses were performed on 182 (93 females and 89 males) elderly participants (mean age: 75.83 ± 1.22). Health status of participants were classified. Sex differences in endothelial function, blood viscosity, high density lipoprotein (HDL), hematocrit, and red blood cell (RBC) aggregation were assessed. CVD prevalence was higher in males (27.0%) than in females (5.4%) (p < 0.001). Females had higher vasoreactivity (p = 0.014) and HDL (p < 0.001) level than males. Blood viscosity was higher in males than in females at any shear rate (p < 0.001). Hematocrit was greater in males than in females (p < 0.001) while RBC aggregation did not differ between the two populations. To conclude, females have less CVD than age-matched males that might be due to their greater vascular function and lower blood viscosity.

Erythrocyte Sedimentation Rate: A Physics-Driven Characterization in a Medical Context.

Erythrocyte (or red blood cell) sedimentation rate (ESR) is a physical derived parameter of blood which is often used in routine health checks and medical diagnosis. For instance, in the case of inflammation, a higher ESR is observed due to the associated increase in fibrinogen and other plasma proteins. It was believed that this increase was due to the formation of larger aggregates of red blood cells (RBCs) caused by the increase in fibrinogen. Indeed, fibrinogen is an agent-fostering aggregation of RBCs and in the Stokes regime-assumed to be observed in blood-larger aggregates sediment faster. However, all models of ESR measurements based on this hypothesis require further specific physical assumptions, not required in any other system. Besides, modern studies in the field of colloidal suspensions have established that attractive particles form percolating aggregates (i.e. aggregates as wide as the container). The sedimentation of these colloids then follows a so-called "colloidal gel collapse". Recently, it has been shown that RBCs actually follow the same behavior. This hypothesis also allows to efficiently and analytically model the sedimentation curve of RBCs, from which robust and physically-meaningful descriptors can be extracted. This manuscript describes how to perform such an analysis, and discusses the benefits of this approach.

Euryale ferox stem-inspired anisotropic quaternized cellulose/xanthan-based antibacterial sponge with high absorbency and compressibility for noncompressible hemorrhage

Uncontrollable hemorrhage from deep noncompressible wounds remains an intractable challenge. Herein, inspired by the euryale ferox stem which is capable of transporting water and nutrient substances efficiently along longitudinally aligned channels, an anisotropic sponge with rapidly liquid absorption capacity, excellent mechanical compressibility and antibacterial property based on quaternized cellulose (QC), xanthan gum (XG) and reduced graphene oxide (rGO), was constructed. The euryale ferox stem-like structure and multiple interactions, involving hydrogen bonding, electrostatic interaction and chemical crosslinking, endowed the sponge with excellent fatigue resistance, elasticity and efficient liquid absorption capacity. In vivo rat liver injury, tail amputation and liver noncompressible hemorrhage model experiments confirmed that the sponge exhibited superior hemostatic performance than commercial gelatin sponge, attributing to the positive charge, efficient absorption capacity and rough surface of the sponge, which synergistically promoting the aggregation and activation of red blood cells and platelets as well as formation of fibrin network, leading to accelerated blood coagulation process. Besides, the sponge showed favorable cytocompatibility, hemocompatibility and antibacterial property. Overall, the bioinspired sponge had fantastic potential for controlling deep noncompressible hemorrhage and providing a new idea for designing hemostatic materials.

Hydroxyethyl Starch-Bovine Hemoglobin Conjugate as an Effective Oxygen Carrier with the Ability to Expand Plasma.

Hemorrhagic shock leads to intravasal volume deficiency, tissue hypoxia, and cellular anaerobic metabolism. Hemoglobin (Hb) could deliver oxygen for hypoxic tissues but is unable to expand plasma. Hydroxyethyl starch (HES) could compensate for the intravasal volume deficiency but cannot deliver oxygen. Thus, bovine Hb (bHb) was conjugated with HES (130 kDa and 200 kDa) to develop an oxygen carrier with the ability to expand plasma. Conjugation with HES increased the hydrodynamic volume, colloidal osmotic pressure, and viscosity of bHb. It slightly perturbed the quaternary structure and heme environment of bHb. The partial oxygen pressures at 50% saturation (P 50) of the two conjugates (bHb-HES130 and bHb-HES200) were 15.1 and 13.9 mmHg, respectively. The two conjugates showed no apparent side effects on the morphology and rigidity, hemolysis, and platelet aggregation of red blood cells of Wistar rats. Thus, bHb-HES130 and bHb-HES200 were expected to function as an effective oxygen carrier with the ability to expand plasma.

In silico modeling of patient-specific blood rheology in type 2 diabetes mellitus

Increased blood viscosity in type 2 diabetes mellitus (T2DM) is a risk factor for the development of insulin resistance and diabetes-related vascular complications; however, individuals with T2DM exhibit heterogeneous hemorheological properties, including cell deformation and aggregation. Using a multiscale red blood cell (RBC) model with key parameters derived from patient-specific data, we present a computational study of the rheological properties of blood from individual patients with T2DM. Specifically, one key model parameter, which determines the shear stiffness of the RBC membrane (μ) is informed by the high-shear-rate blood viscosity of patients with T2DM. At the same time, the other, which contributes to the strength of the RBC aggregation interaction (D0), is derived from the low-shear-rate blood viscosity of patients with T2DM. The T2DM RBC suspensions are simulated at different shear rates, and the predicted blood viscosity is compared with clinical laboratory-measured data. The results show that the blood viscosity obtained from clinical laboratories and computational simulations are in agreement at both low and high shear rates. These quantitative simulation results demonstrate that the patient-specific model has truly learned the rheological behavior of T2DM blood by unifying the mechanical and aggregation factors of the RBCs, which provides an effective way to extract quantitative predictions of the rheological properties of the blood of individual patients with T2DM.

Albumin effect on hemorheological parameters in patients with liver transplant.

Liver transplantation is a life-saving treatment in end-stage liver failure. Hemorheological features as blood fluidity and red blood cell aggregation may alter effective tissue perfusion, graft function and hemodynamic variables. The aim of the study is to investigate effect of albumin infusion on red blood cell deformability and aggregation, blood viscosity and hemodynamics in liver transplant patients. Seventeen live or cadaveric donors were included in this prospective study. Hemorheological and hemodynamic measurements were performed in order to evaluate the effects of albumin infusion in perioperative period. Erythrocyte aggregation was significantly reduced 90 minutes after albumin infusion (p < 0.01). Mean blood viscosity revealed significant decrease at 20 rpm and 50 rpm after 90 minutes of albumin infusion (p < 0.05). Plasma viscosity decreased significantly compared to the value before albumin infusion at 20 rpm (p < 0.05). Albumin replacement improved hemodynamic variables in patients with low blood pressure and cardiac index measurements (p > 0.05). Human albumin infusion led to decrease in whole blood and plasma viscosities, red blood cell aggregation and induced blood pressure and cardiac index elevation in perioperative liver transplant patients. Determination of hemodynamic and hemorheological effects of human albumin replacement in various patient populations may serve beneficial clinical data.

Effect of Clutter Filter in High-Frame-Rate Ultrasonic Backscatter Coefficient Analysis.

High-frame-rate imaging with a clutter filter can clearly visualize blood flow signals and provide more efficient discrimination with tissue signals. In vitro studies using clutter-less phantom and high-frequency ultrasound suggested a possibility of evaluating the red blood cell (RBC) aggregation by analyzing the frequency dependence of the backscatter coefficient (BSC). However, in in vivo applications, clutter filtering is required to visualize echoes from the RBC. This study initially evaluated the effect of the clutter filter for ultrasonic BSC analysis for in vitro and preliminary in vivo data to characterize hemorheology. Coherently compounded plane wave imaging at a frame rate of 2 kHz was carried out in high-frame-rate imaging. Two samples of RBCs suspended by saline and autologous plasma for in vitro data were circulated in two types of flow phantoms without or with clutter signals. The singular value decomposition was applied to suppress the clutter signal in the flow phantom. The BSC was calculated using the reference phantom method, and it was parametrized by spectral slope and mid-band fit (MBF) between 4-12 MHz. The velocity distribution was estimated by the block matching method, and the shear rate was estimated by the least squares approximation of the slope near the wall. Consequently, the spectral slope of the saline sample was always around four (Rayleigh scattering), independently of the shear rate, because the RBCs did not aggregate in the solution. Conversely, the spectral slope of the plasma sample was lower than four at low shear rates but approached four by increasing the shear rate, because the aggregations were presumably dissolved by the high shear rate. Moreover, the MBF of the plasma sample decreased from -36 to -49 dB in both flow phantoms with increasing shear rates, from approximately 10 to 100 s-1. The variation in the spectral slope and MBF in the saline sample was comparable to the results of in vivo cases in healthy human jugular veins when the tissue and blood flow signals could be separated.

Effects of rapid gravity load changes on immunophenotyping and leukocyte function of human peripheral blood after parabolic flight

One of the biological systems that suffers a physiological de-conditioning in space is the immune system. It is in charge of defending the body against pathogens and other aggressions. The aim of this work was to assess if there are any relevant changes in the aggregation of erythrocytes, cell count, immunophenotyping and functionality after parabolic flight. This effect has been assessed ex vivo using human peripheral blood, which was drawn from the radial vein (n = 6 healthy volunteers) and anticoagulated with heparin and EDTA. Blood samples were split into two aliquots and maintained in two identical thermally isolated boxes; one stayed on the ground whereas the other one was subjected to parabolic flight. The parabolic flight consisted of 15 parabolas performed with a Mudry CAP-10B acrobatic aircraft. Each parabola consists of 8 s of hypogravity preceded and followed by 2 s of hypergravity. Any of the biological parameters measured showed no statistically significant differences, with the exception of monocyte counting. Altered gravity could increase aggregation of red blood cells, as demonstrated by a decrease in the number of single cells after parabolic flight exposure. No counting changes in haemoglobin concentration were observed when comparing the two different groups. Furthermore, potential functional alterations of monocytes and neutrophils cannot be rejected. Although these possible changes could be associated with hypogravity, other factors such as hypergravity and acceleration or deceleration cannot be ruled out. Our findings indicate that, under this specific experimental setup, there was no significant alteration in leukocyte immunophenotyping and functional capacity when using ex vivo blood samples and short exposure to altered gravity.

In vivo measurement of attenuation coefficient of blood in a dorsal hand vein in a frequency range of 10–45 MHz: A preliminary study

In this study, the attenuation coefficient of blood was measured in vivo in the frequency range of 10–45 MHz. A procedure to correct the distribution of sound pressure in the measurements was discussed. Further, in vivo measurements were applied on the dorsal hand vein of four healthy subjects at rest and during avascularization. As a preliminary result, less variation of the measured attenuation coefficients was achieved by the proposed method. The comparable results of the inclination of the attenuation coefficients were obtained at rest and during avascularization. Furthermore, the attenuation coefficients during avascularization were markedly higher than those at rest, reflecting the degree of red blood cell aggregation promoted by avascularization. This method may aid in the non-invasive evaluation of blood properties reflecting the degree of red blood cell aggregation.

Biomechanical Assessment of Red Blood Cells in Pulsatile Blood Flows

As rheological properties are substantially influenced by red blood cells (RBCs) and plasma, the separation of their individual contributions in blood is essential. The estimation of multiple rheological factors is a critical issue for effective early detection of diseases. In this study, three rheological properties (i.e., viscoelasticity, RBC aggregation, and blood junction pressure) are measured by analyzing the blood velocity and image intensity in a microfluidic device. Using a single syringe pump, the blood flow rate sets to a pulsatile flow pattern (Qb[t] = 1 + 0.5 sin(2πt/240) mL/h). Based on the discrete fluidic circuit model, the analytical formula of the time constant (λb) as viscoelasticity is derived and obtained at specific time intervals by analyzing the pulsatile blood velocity. To obtain RBC aggregation by reducing blood velocity substantially, an air compliance unit (ACU) is used to connect polyethylene tubing (i.d. = 250 µm, length = 150 mm) to the blood channel in parallel. The RBC aggregation index (AI) is obtained by analyzing the microscopic image intensity. The blood junction pressure (β) is obtained by integrating the blood velocity within the ACU. As a demonstration, the present method is then applied to detect either RBC-aggregated blood with different concentrations of dextran solution or hardened blood with thermally shocked RBCs. Thus, it can be concluded that the present method has the ability to consistently detect differences in diluent or RBCs in terms of three rheological properties.

Effects of a Maximal Exercise Followed by a Submaximal Exercise Performed in Normobaric Hypoxia (2500 m), on Blood Rheology, Red Blood Cell Senescence, and Coagulation in Well-Trained Cyclists.

Acute normoxic exercise impacts the rheological properties of red blood cells (RBC) and their senescence state; however, there is a lack of data on the effects of exercise performed in hypoxia on RBC properties. This crossover study compared the effects of acute hypoxia vs. normoxia on blood rheology, RBC senescence, and coagulation during exercise. Nine trained male cyclists completed both a session in normoxia (FiO2 = 21%) and hypoxia (FiO2 = 15.3% ≈ 2500 m). The two sessions were randomly performed, separated by one week, and consisted of an incremental and maximal exercise followed by a 20 min exercise at the first ventilatory threshold (VT1) on a home-trainer. Blood samples were taken before and after exercise to analyze hematological parameters, blood rheology (hematocrit, blood viscosity, RBC deformability and aggregation), RBC senescence markers (phosphatidylserine (PS) and CD47 exposure, intraerythrocyte reactive oxygen species (ROS), and calcium content), and blood clot viscoelastic properties. Hemoglobin oxygen saturation (SpO2) and blood lactate were also measured. In both conditions, exercise induced an increase in blood viscosity, hematocrit, intraerythrocyte calcium and ROS content, and blood lactate concentration. We also observed an increase in blood clot amplitude, and a significant drop in SpO2 during exercise in the two conditions. RBC aggregation and CD47 exposure were not modified. Exercise in hypoxia induced a slight decrease in RBC deformability which could be related to the slight increase in mean corpuscular hemoglobin concentration (MCHC). However, the values of RBC deformability and MCHC after the exercise performed in hypoxia remained in the normal range of values. In conclusion, acute hypoxia does not amplify the RBC and coagulation changes induced by an exercise bout.

A local-saturation-and-delay MRI method for evaluation of red blood cells aggregation in vivo for tumor-bearing or drug-used rats.

Hyperviscosity syndrome (HVS) is a combination of clinical signs and symptoms related to increased blood viscosity. HVS can increase the thrombotic risk by causing a major disturbance to the blood flow, which is usually found in the advanced stages of the tumor. Moreover, some of the drugs used in chemotherapy, such as 5-fluorouracil and erythropoietin, are also capable of causing HVS through their respective pathways. Clinically, the viscosity of a patient's blood sample is measured by a rotary rheometer to estimate the risk of hyperviscosity syndrome. However, the measurement of blood viscosity in vitro is easily affected by storage time, storage environment, and anticoagulants. In addition, the fluid conditions in the rheometer are quite different from those in natural blood vessels, making this method inappropriate for evaluating blood viscosity and its effects in vivo under physiological condition. Herein, we presented a novel magnetic resonance imaging method called local-saturation-and-delay imaging (LSDI). The radial distributions of flow velocity measured by LSDI are consistent with the Ultrasonic (US) method (Spearman correlation coefficient r = 0.990). But the result of LSDI is more stable than US (p < 0.0001). With the LSDI method, we can directly measure the radial distribution of diastolic flow velocity, and further use these data to calculate the whole blood relative viscosity (WBRV) and erythrocyte aggregation trend. It was a strong correlation between the results measured by LSDI and rotary rheometer in the group of rats given erythropoietin. Furthermore, experimental results in glioma rats indicate that LSDI is equivalent to a rheometer as a method for predicting the risk of hyperviscosity syndrome. Therefore, LSDI, as a non-invasive method, can effectively follow the changes in WBRV in rats and avoid the effect of blood sampling during the experiment on the results. In conclusion, LSDI is expected to become a novel method for real-time in vivo recognition of the cancer progression and the influence of drugs on blood viscosity and RBC aggregation.

Journey of micronanoplastics with blood components.

The entry of micro- and nanoplastics (MNPs) into the human body is inevitable. They enter blood circulation through ingestion, inhalation, and dermal contact by crossing the gut-lung-skin barrier (the epithelium of the digestive tract, the respiratory tract, and the cutaneous layer). There are many reports on their toxicities to organs and tissues. This paper presents the first thorough assessment of MNP-driven bloodstream toxicity and the mechanism of toxicity from the viewpoint of both MNP and environmental co-pollutant complexes. Toxic impacts include plasma protein denaturation, hemolysis, reduced immunity, thrombosis, blood coagulation, and vascular endothelial damage, among others, which can lead to life-threatening diseases. Protein corona formation, oxidative stress, cytokine alterations, inflammation, and cyto- and genotoxicity are the key mechanisms involved in toxicity. MNPs change the secondary structure of plasma proteins, thereby preventing their transport functions (for nutrients, drugs, oxygen, etc.). MNPs inhibit erythropoiesis by influencing hematopoietic stem cell proliferation and differentiation. They cause red blood cell and platelet aggregation, as well as increased adherence to endothelial cells, which can lead to thrombosis and cardiovascular disease. White blood cells and immune cells phagocytose MNPs, provoking inflammation. However, research gaps still exist, including gaps regarding the combined toxicity of MNPs and co-pollutants, toxicological studies in human models, advanced methodologies for toxicity analysis, bioaccumulation studies, inflammation and immunological responses, dose-response relationships of MNPs, and the effect of different physiochemical characteristics of MNPs. Furthermore, most studies have analyzed toxicity using prepared MNPs; hence, studies must be undertaken using true-to-life MNPs to determine the real-world scenario. Additionally, nanoplastics may further degrade into monomers, whose toxic effects have not yet been explored. The research gaps highlighted in this review will inspire future studies on the toxicity of MNPs in the vascular/circulatory systems utilizing in vivo models to enable more reliable health risk assessment.

Anisotropic short-range attractions precisely model branched erythrocyte aggregates.

Homogeneous suspensions of red blood cells (RBCs or erythrocytes) in blood plasma are unstable in the absence of driving forces and form elongated stacks, called rouleaux. These erythrocyte aggregates are often branched porous networks - a feature that existing red blood cell aggregation models and simulations fail to predict exactly. Here we establish that alignment-dependent attractive forces in a system of dimers can precisely generate branched structures similar to RBC aggregates observed under a microscope. Our simulations consistently predict that the growth rate of typical mean rouleau size remains sub-linear - a hallmark from past studies - which we also confirm by deriving a reaction kernel taking into account appropriate collision cross-section, approach velocities, and an area-dependent sticking probability. The system exhibits unique features such as the existence of percolated and/or single giant cluster states, multiple coexisting mass-size scalings, and transition to a branched phase upon fine-tuning of model parameters. Upon decreasing the depletion thickness we find that the percolation threshold increases but the morphology of the structures opens up towards an increased degree of branching. Remarkably the system self-organizes to produce a universal power-law size distribution scaling irrespective of the model parameters.

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 (β). Two parameters (i.e., average value: <λ>, linear slope: dλdβ) were newly suggested to effectively represent linearly varying time constant. <λ> exhibited more consistent results than dλdβ. 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.

Possibility of Red Blood Cell Changes after COVID-19 Pandemic

Dear editor,&#x0D; &#x0D; The COVID-19 pandemic caused a lot of changes in society and the economy as well as individual, physical, and mental health. COVID-19 might cause acute respiratory syndrome, coagulopathy, vascular failure, and organ damage1-3. In the study by Huang L et al., 2469 patients who recovered from severe COVID-19 were followed up for two years, the longest follow-up until now. They demonstrated that COVID-19 survivors had remarkably lower health status than the general population after two years and suggested urgent exploration into the pathogenesis of the disease4. Otherwise, there were some important issues with this study. First, it was not an international study that included different geographic regions, ethnicities, races, and countries. Another important point was that 80 percent of patients experienced mild or no symptoms of this disease which were excluded from this study. However, COVID -19 affected their health conditions as well as severe patients. It is clear that exposure to the virus in the recent pandemic is unavoidable and no one can be sure about the previous infection of the studied cases.Furthermore, many people were reluctant to take a PCR test despite mild symptoms and also, the PCR test has a high false-negative rate, which is affected by the sampling method and the time of interval5, 6. It is suggested researchers investigate the COVID-19 effects on the general population.&#x0D; Most COVID-19 patients reported breathlessness and reduced fitness, which might be related to pulmonary damage and altered oxygen uptake into the red blood cells (RBC), leading to hypoxemia.&#x0D; Some studies demonstrated that COVID-19 altered RBC morphology and revealed a higher percentage of elongated RBC(7). The RBC deformability was significantly increased in COVID-19 patients7. Nader et al. showed that RBC aggregation increased in COVID-19 patients and correlated positively with the hospitalization length8. In a recent study, it was found that oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1) may cause RBCs disability in COVID- 19 patients, who could respond to environmental changes in hemoglobin oxygen saturation/oxidant stress. Nonetheless, there were no alterations in hematological parameters, such as RBC count, hematocrit, or mean corpuscular hemoglobin concentration9. Based on these reports, the count of normal RBC is admissible, but maybe the function of RBCs in oxygen transfer have changes.&#x0D; The above-mentioned studies indicated the temporary effects of COVID-19 on RBCS, but COVID-19 may cause some long-term effects on RBCs10. There is enough evidence indicating that the numbers of RBC and hematocrit (HCT) increase significantly in response to hypoxic environments, similar to changes that occur by living in high-altitude places11. With the large-scale outbreak of the COVID epidemic worldwide, the number of people using protective masks has increased rapidly. Using masks can cause problems, such as hypoxia symptoms, which increase RBC mass and HCT for a long time12,13. According to recent studies, wearing a mask can alter peripheral Spo2 after two hours, and it can cause small but significant changes in cerebral blood flow (CBF) and cerebral blood oxygen saturation (StO2) while wearing diffrent types of masks (surgical and FFP2)14,15.&#x0D; Based on the above-mentioned studies, the significant changes in RBC functions after the COVID-19 pandemic can be concluded, however the definitive diagnosis is not possible using routine laboratory tests. According to long-term changes in RBC count, the lack of any population-based studies on RBC changes before and after the COVID-19 pandemic, and the key role of RBC count in diagnosing disease, especially in anemia, more investigations seem to be necessary. Reference intervals need to be re-examined in the new health conditions after the COVID-19 pandemic.

Hemorheological and Microcirculatory Relations of Acute Pancreatitis.

Acute pancreatitis still means a serious challenge in clinical practice. Its pathomechanism is complex and has yet to be fully elucidated. Rheological properties of blood play an important role in tissue perfusion and show non-specific changes in acute pancreatitis. An increase in blood and plasma viscosity, impairment of red blood cell deformability, and enhanced red blood cell aggregation caused by metabolic, inflammatory, free radical-related changes and mechanical stress contribute to the deterioration of the blood flow in the large vessels and also in the microcirculation. Revealing the significance of these changes in acute pancreatitis may better explain the pathogenesis and optimize the therapy. In this review, we give an overview of the role of impaired microcirculation by changes in hemorheological properties in acute pancreatitis.