Whole blood PT/aPTT assay based on non-contact drop-of-sample acoustic tweezing spectroscopy.

Most coagulation tests are photo-optical turbidimetric assays that require the removal of cellular components from whole blood for optical clearing. If the resulting blood plasma samples are hemolyzed, they may become unsuitable for turbidimetric analysis. To resolve this issue, whole-blood analogs to plasma turbidimetric assays need to be developed. Using samples collected from non-smokers (normal group), smokers (thrombotic group), and hemophilia A (bleeding group) patients, we demonstrate that the reaction time assessed from whole blood viscosity data of the drop-of-blood acoustic tweezing spectroscopy (ATS) technique strongly correlates (Rp ≥ 0.95) with PT/aPTT values obtained from plasma turbidimetric data. Linear correlation (Rp ≥ 0.88) was also obtained between the viscous and elastic outputs of the ATS technique and the fibrinogen concentration. The integration of ATS data enabled the assessment of the functional level of fibrin cross-linkers such as factor XIII. Overall, ATS allows comprehensive sample-sparing analysis of whole blood coagulation for reliable and safe diagnosis of bleeding/thrombosis risks.

Discrimination of the acute pulmonary embolism subtypes based on the novel MAPH score.

Acute pulmonary embolism (APE) is a thromboembolism situation that can be central or peripheral. APE risk analysis and classification are essential for therapy planning. Our aim is to determine the novel MAPH score (including age, mean platelet volume (MPV), total protein, and hematocrit parameters) that can distinguish APE subtypes. Our retrospective cohort analysis includes 97 APE patients referred to the emergency medicine department who underwent pulmonary computed tomography angiography (CTA) in 24 h from 2020 to 2022. The hospital information system provided demographic, clinical, laboratory, and pulmonary CTA data. APE was classified into central (46 patients) and peripheral (51 patients) depending on the area of vascular involvement. The central APE group had higher hypertension (HT) (67.4%) and atrial fibrillation (AF) (39.1%) incidence than the peripheral APE group (all p values > 0.05). The central APE had higher total protein and platelet counts (p = 0.003 and p = 0.036), but peripheral APE had higher troponin values (p = 0.029). Central APE had 2.17 ± 0.85 MAPH and peripheral APE 1.76 ± 0.95 (p = 0.029). HT, AF, platelet count, and MAPH score differed significantly in univariate logistic regression (all p values < 0.05). However, only platelet count varied in multivariate logistic regression (p = 0.042). ROC curve analysis revealed that the MAPH score predicts central APE with 83% sensitivity and 45% specificity at a cut-off level of 1.5. The new MAPH score as an indicator of blood viscosity may distinguish between central and peripheral APE. Our result is significant, especially for centers with limited examinations, as it may accelerate the diagnosis and treatment processes. We think that our results might guide future investigations.

Influence of a Decrease in Blood Viscosity on Arterial Pressure in Normotensive and Spontaneously Hypertensive Rats.

We investigated the effect of a decrease in blood viscosity on the mean BP during isovolumic hemodilution and vasodilating activity of the endothelium in normotensive Wistar rats and spontaneously hypertensive rats (SHR). Blood viscosity was reduced by isovolumic hemodilution (replacement of 10% of circulating blood with an equal volume of plasma). Hemodilution caused the same reduction in blood viscosity by 16% in both groups of rats. In Wistar rats, a decrease in blood viscosity did not significantly change in the mean BP; no significant correlations between blood viscosity and mean BP were observed before and after hemodilution. In SHR, a decrease in blood viscosity led to a significant decrease in the mean BP by 18%. Correlations were found between the mean BP and blood viscosity in SHR before (r=0.63; p=0.028) and after (r=0.71; p=0.009) isovolumic hemodilution. In SHR, a decrease in the index of vasodilating activity of the endothelium due to a decrease in the vasodilatory response to intravenous administration of the endothelium-dependent vasodilator acetylcholine was revealed. In SHR, BP passively follows the change, in this case, the decrease in blood viscosity, which attests to impaired BP regulation in response to changes in shear stress on the vascular endothelium caused by the development of endothelial dysfunction in hypertensive animals.

Association of haemolysis markers, blood viscosity and microcirculation function with organ damage in sickle cell disease in sub-Saharan Africa (the BIOCADRE study).

Sickle cell anaemia (SCA) is a monogenic disease with a highly variable clinical course. We aimed to investigate associations between microvascular function, haemolysis markers, blood viscosity and various types of SCA-related organ damage in a multicentric sub-Saharan African cohort of patients with SCA. In a cross-sectional study, we selected seven groups of adult patients with SS phenotype in Dakar and Bamako based on the following complications: leg ulcer, priapism, osteonecrosis, retinopathy, high tricuspid regurgitant jet velocity (TRV), macro-albuminuria or none. Clinical assessment, echocardiography, peripheral arterial tonometry, laboratory tests and blood viscosity measurement were performed. We explored statistical associations between the biological parameters and the six studied complications. Among 235 patients, 58 had high TRV, 46 osteonecrosis, 43 priapism, 33 leg ulcers, 31 retinopathy and 22 macroalbuminuria, whereas 36 had none of these complications. Multiple correspondence analysis revealed no cluster of complications. Lactate dehydrogenase levels were associated with high TRV, and blood viscosity was associated with retinopathy and the absence of macroalbuminuria. Despite extensive phenotyping of patients, no specific pattern of SCA-related complications was identified. New biomarkers are needed to predict SCA clinical expression to adapt patient management, especially in Africa, where healthcare resources are scarce.

Effects of sarpogrelate on blood viscosity.

The objective of the present study was to evaluate the effects and safety of sarpogrelate hydrochloride (sarpogrelate) in patients with elevated blood viscosity (BV), after 12 and 24 weeks of twice (BID) or thrice (TID) daily administrations of sarpogrelate (100 mg). The participants received oral sarpogrelate administration for 24 weeks and visited the hospital every 12 ± 2 week for blood viscosity measurements at shear rates of 5 and 300 s-1. The BV measured at shear rate of 5 s-1 in male patients decreased significantly from 18.91 cP at the baseline to 16.3 cP after 24 weeks of sarpogrelate administration (13.6 % drop, p < 0.001). The BV measured at 5 s-1 in female decreased more significantly from 17.5 cP at the baseline to 13.4 cP after 24 weeks of sarpogrelate administration (23.0 % drop, p < 0.001). In summary, sarpogrelate may be considered as a possible therapeutic option for improving BV in patients with elevated blood viscosity. In particular, the reduction of the low-shear BV with the help of a viscosity-reducing drug such as sarpogrelate may be considered as a potentially new pharmacological tool for microvascular disease.

Single-night continuous positive airway pressure treatment improves blood fluid properties in individuals recently diagnosed with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a prevalent disorder that causes repetitive, temporary collapses of the upper airways during sleep, resulting in intermittent hypoxaemia and sleep fragmentation. Given those with OSA also exhibit decreased blood fluidity, this clinical population is at heightened risk for cardiovascular disease (CVD) development. Continuous positive airway pressure (CPAP) remains a primary therapy in OSA, which improves sleep quality and limits sleep fragmentation. While CPAP effectively ameliorates nocturnal hypoxic events and associated arousals, it remains unclear whether CVD risk factors are positively impacted. The aim of the present study was thus to assess the effects of an acute CPAP therapy on sleep quality and the physical properties of blood that determine blood fluidity. Sixteen participants with suspected OSA were recruited into the current study. Participants attended the sleep laboratory for two visits: an initial diagnostic visit that included confirmation of OSA severity and comprehensive assessments of blood parameters, followed by a subsequent visit where participants were administered an individualised, acute CPAP therapy session and had their blood assessments repeated. Holistic appraisal of blood rheological properties included assessment of blood and plasma viscosity, red blood cell (RBC) aggregation, deformability, and osmotic gradient ektacytometry. Acute CPAP treatment significantly improved sleep quality parameters, which were associated with decreased nocturnal arousals and improved blood oxygen saturation. Whole blood viscosity was significantly decreased following acute CPAP treatment, which might be explained by the improved RBC aggregation during this visit. Although an acute increase in plasma viscosity was observed, it appears that the alterations in RBC properties that mediate cell-cell aggregation, and thus blood viscosity, overcame the increased plasma viscosity. While deformability of RBC was unaltered, CPAP therapy had mild effects on the osmotic tolerance of RBC. Collectively, novel observations demonstrate that a single CPAP treatment session acutely improved sleep quality, which was accompanied by improved rheological properties.

A theoretical model for the Fåhræus effect in medium-large microvessels.

This paper presents a mathematical model capable to reproduce a celebrated phenomenon in blood microcirculation known as Fåhræus effect, since its discovery by Robin Fåhræus (1929). This consists in a decaying of the relative hematocrit in small vessels as the vessel diameter decreases. The key point of the model is a formula, direct consequence of the basic principles of fluid dynamics, that links the relative hematocrit to the reservoir hematocrit and the vessel diameter, which confirms the observed behavior. To test the model we selected, among the few experiments carried on since then, those performed by Barbee and Cokelet (1971). The agreement is remarkable. An extended comparison is also carried out with a celebrated empirical formula proposed by Pries et al. (1992) to describe the same phenomenon.

Influence of blood viscosity models and boundary conditions on the computation of hemodynamic parameters in cerebral aneurysms using computational fluid dynamics.

BACKGROUND: Computational fluid dynamics (CFD) is widely used to calculate hemodynamic parameters that are known to influence cerebral aneurysms. However, the boundary conditions for CFD are chosen without any specific criteria. Our objective is to establish the recommendations for setting the analysis conditions for CFD analysis of the cerebral aneurysm. METHOD: The plug and the Womersley flow were the inlet boundary conditions, and zero and pulsatile pressures were the outlet boundary conditions. In addition, the difference in the assumption of viscosity was analyzed with respect to the flow rate. The CFD process used in our research was validated using particle image velocimetry experiment data from Tupin et al.'s work to ensure the accuracy of the simulations. RESULTS: It was confirmed that if the entrance length was sufficiently secured, the inlet and outlet boundary conditions did not affect the CFD results. In addition, it was observed that the difference in the hemodynamic parameter between Newtonian and non-Newtonian fluid decreased as the flow rate increased. Furthermore, it was confirmed that similar tendencies were evaluated when these recommendations were utilized in the patient-specific cerebral aneurysm models. CONCLUSIONS: These results may help conduct standardized CFD analyses regardless of the research group.

Effects on blood parameters from hand-arm vibrations exposure.

Vibration exposure from handheld tools can affect the hands with neurological symptoms and vibration-induced Raynaud's phenomenon (VRP). The underlying pathophysiological mechanisms are not fully known, however, changes in the composition of blood parameters may contribute to VRP with an increase in blood viscosity and inflammatory response. The aim of this study was to examine the effect on blood parameters in capillary blood from fingers that had been exposed to a vibrating hand-held tool. This study involved nine healthy participants who had been exposed to vibration and an unexposed control group of six participants. Capillary blood samples were collected before and after vibration exposure for the exposed group, and repeated samples also from the control group. The exposed groups were exposed to vibration for a 15-min period or until they reached a 5.0 m/s2 vibration dose. Analysis of blood status and differential counting of leucocytes was performed on the capillary blood samples. The results of the blood samples showed an increase in mean value for erythrocyte volume fraction (EVF), hemoglobin, red blood cell count, white blood cell count and neutrophils, as well as a decrease of mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration. The increase of EVF and neutrophils was statistically significant for samples taken from the index finger but not the little finger. Even though the study was small it showed that an acute vibration exposure to the hands might increase EVF and neutrophilic granulocytes levels in the capillary blood taken from index fingers.

Hypolipidemic and Anti-Inflammatory Effects of Curcuma longa-Derived Bisacurone in High-Fat Diet-Fed Mice.

Turmeric (Curcuma longa) contains various compounds that potentially improve health. Bisacurone is a turmeric-derived compound but has been less studied compared to other compounds, such as curcumin. In this study, we aimed to evaluate the anti-inflammatory and lipid-lowering effects of bisacurone in high-fat diet (HFD)-fed mice. Mice were fed HFD to induce lipidemia and orally administered bisacurone daily for two weeks. Bisacurone reduced liver weight, serum cholesterol and triglyceride levels, and blood viscosity in mice. Splenocytes from bisacurone-treated mice produced lower levels of the pro-inflammatory cytokines IL-6 and TNF-α upon stimulation with a toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS), and TLR1/2 ligand, Pam3CSK4, than those from untreated mice. Bisacurone also inhibited LPS-induced IL-6 and TNF-α production in the murine macrophage cell line, RAW264.7. Western blot analysis revealed that bisacurone inhibited the phosphorylation of IKKα/ß and NF-κB p65 subunit, but not of the mitogen-activated protein kinases, p38 kinase and p42/44 kinases, and c-Jun N-terminal kinase in the cells. Collectively, these results suggest that bisacurone has the potential to reduce serum lipid levels and blood viscosity in mice with high-fat diet-induced lipidemia and modulate inflammation via inhibition of NF-κB-mediated pathways.

Effectiveness and Safety of Fufang Danshen Dripping Pill (Cardiotonic Pill) on Blood Viscosity and Hemorheological Factors for Cardiovascular Event Prevention in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.

Background and Objectives: Diabetes can cause various vascular complications. The Compounded Danshen-Dripping-Pill (CDDP) is widely used in China. This study aimed to analyze the effectiveness and safety of CDDP in the blood viscosity (BV) with type 2 diabetes mellitus (T2DM). Materials and Methods: We conducted a systematic search of seven databases from their inception to July 2022 for randomized controlled trials that used CDDP to treat T2DM. To evaluate BV, we measured low shear rate (LSR), high shear rate (HSR), and plasma viscosity (PV). Homocysteine and adiponectin levels were also assessed as factors that could affect BV. Results: We included 18 studies and 1532 patients with T2DM. Meta-analysis revealed that CDDP significantly reduced LSR (mean difference [MD] -2.74, 95% confidence interval [CI] -3.77 to -1.72), HSR (MD -0.86, 95% CI -1.08 to -0.63), and PV (MD -0.37, 95% CI -0.54 to -0.19) compared to controls. CDDP also reduced homocysteine (MD -8.32, 95% CI -9.05 to -7.58), and increased plasma adiponectin (MD 2.72, 95% CI 2.13 to 3.32). Adverse events were reported less frequently in the treatment groups than in controls. Conclusions: CDDP is effective in reducing BV on T2DM. However, due to the poor design and quality of the included studies, high-quality, well-designed studies are required in the future.

Impact of small fractions of abnormal erythrocytes on blood rheology.

Red blood cell (RBC) populations are inherently heterogeneous, given mature RBC lack the transcriptional machinery to re-synthesize proteins affected during in vivo aging. Clearance of older, less functional cells thus aids in maintaining consistent hemorheological properties. Scenarios occur, however, where portions of mechanically impaired RBC are re-introduced into blood (e.g., damaged from circulatory support, blood transfusion) and may alter whole blood fluid behavior. Given such perturbations are associated with poor clinical outcomes, determining the tolerable level of abnormal RBC in blood is valuable. Thus, the current study aimed to define the critical threshold of blood fluid properties to re-infused physically-impaired RBC. Cell mechanics of RBC were impaired through membrane cross-linking (glutaraldehyde) or intracellular oxidation (phenazine methosulfate). Mechanically impaired RBC were progressively re-introduced into the native cell population. Negative alterations of cellular deformability and high shear blood viscosity were observed following additions of only 1-5% rigidified RBC. Low-shear blood viscosity was conversely decreased following addition of glutaraldehyde-treated cells; high-resolution microscopy of these mixed cell populations revealed decreased capacity to form reversible aggregates and decreased aggregate size. Mixed RBC populations, when exposed to supraphysiological shear, presented with compounded mechanical impairment. Collectively, key determinants of blood flow behavior are sensitive to mechanical perturbations in RBC, even when only 1-5% of the cell population is affected. Given this fraction is well-below the volume of rigidified RBC introduced during circulatory support or transfusion practice, it is plausible that some adverse events following surgery and/or transfusion may be related to impaired blood fluidity.

Improved Erythrocyte Deformability Induced by Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetic Patients.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are antidiabetic drugs that improve cardiovascular outcomes. Hemoglobin and hematocrit values increase after SGLT-2 inhibitor administration. Although these factors increase blood viscosity and the risk of cardiovascular disease, SGLT-2 inhibitors have protective effects on the cardiovascular system. The mechanisms for this paradoxical phenomenon remain unclear, and the effect of SGLT-2 inhibitors on hemorheology has not been studied. METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Blood viscosity was measured using a cone-and-plate viscometer, erythrocyte aggregation was measured using a modified erythrocyte sedimentation rate method, and erythrocyte membrane fluctuation was measured as deformability, using a diffraction optical tomography. RESULTS: Both blood viscosity and erythrocyte aggregation increased in the SGLT-2 inhibitor group, although erythrocyte deformability was significantly improved compared with that of the DPP-4 inhibitor group (DPP-4 inhibitor 43.71 ± 5.13 nm; SGLT-2 inhibitor 53.88 ± 4.88 nm; p < 0.001). When the two groups were compared after propensity score matching, no differences in blood viscosity at high shear rates and erythrocyte aggregation were observed, although erythrocyte deformability was significantly improved in the SGLT-2 inhibitor group (DPP-4 inhibitor 45.01 ± 5.28 nm; SGLT-2 inhibitor 53.14 ± 4.72 nm; p = 0.001). CONCLUSION: This study demonstrates that erythrocyte deformability was improved in the SGLT-2 inhibitor group compared with that in the DPP-4 inhibitor group. This improvement in erythrocyte deformability is expected to have a protective effect on the cardiovascular system.

Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke.

Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2 h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.

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.

Comparing of Frequency Shift and Impedance Analysis Method Based on QCM Sensor for Measuring the Blood Viscosity.

Blood viscosity measurements are crucial for the diagnosis of cardiovascular and hematological diseases. Traditional blood viscosity measurements have obvious limitations because of their expensive equipment usage and large sample consumption. In this study, blood viscosity was measured by the oscillating circuit method and impedance analysis method based on single QCM. In addition, the effectiveness of two methods with high precision and less sample is proved by the experiments. Moreover, compared to the result from a standard rotational viscometer, the maximum relative errors of the proposed oscillating circuit method and impedance analysis method are ±5.2% and ±1.8%, respectively. A reliability test is performed by repeated measurement (N = 5), and the result shows that the standard deviation about 0.9% of impedance analysis is smaller than that of oscillating circuit method. Therefore, the impedance analysis method is superior. Further, the repeatability of impedance analysis method was evaluated by regression analysis method, and the correlation coefficient R2 > 0.965 demonstrated that it had excellent reproducibility.

Another possible determinant for ischemic stroke with nonvalvular atrial fibrillation other than conventional oral anticoagulant treatment: The relationship between whole blood viscosity and stroke☆.

OBJECTIVES: Patients with nonvalvular atrial fibrillation (NVAF) still experience ischemic stroke despite recommended medications and this could be the consequence of increased whole blood viscosity (WBV). We evaluated the predictive value of WBV for stroke in patients with NVFA despite receiving oral anticoagulant (OAC) therapy. METHODS: One thousand and forty-three NVAF patients on OAC medication were followed up for median 36.13 ± 18.31 months. WBV was calculated according to the validated de Simone's formula. RESULTS: WBV was significantly higher in stroke group when compared to non-stroke group at both low shear rate (LSR) and high shear rate (HSR). Multiple regression analysis demonstrated an independent association between WBV and stroke when adjusted for other risk factors. CONCLUSIONS: WBV appears to be a profitable predictor of ischemic stroke in patients with NVAF receiving OAC.

Elevated blood viscosity is associated with delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Delayed cerebral ischemia (DCI) is a contributing factor for poor clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). Blood viscosity can reflect flow resistance and dehydration status. Our study aimed to analyze the association between blood viscosity and DCI in patients with aSAH. METHODS: In this retrospective cohort, systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) were measured at admission in patients with aSAH. Receiver operating characteristic curve analysis was used to assess the predictive values of SBV and DBV for DCI after aSAH. Univariate and multivariate logistic regression was performed to analyze the association between blood viscosity and the development of DCI. RESULTS: A total of 470 patients with aSAH were included in this study, and 184 (39.1%) patients had DCI. Optimal cut-off values of DBV and SBV were presented as 12.05 (cP) and 3.75 (cP), respectively. In addition, DBV has higher predictable value of DCI than SBV (DBV: area under the curve [AUC] 0.793; standard error [SE] 0.026; 95% CI 0.722-0.864; P < 0.001, and SBV: AUC 0.702; SE 0.040; 95% CI 0.624-0.781; P < 0.001). In multivariate logistic regression analysis, elevated DBV was a predicting factor for development of DCI (odds ratio: 1.60; 95% confidence interval: 1.32-2.58; P = 0.037). CONCLUSIONS: Blood viscosity is associated with development of DCI in patients with aSAH. Especially, DBV has a higher predictive value for the occurrence of DCI than SBV. Elevated DBV is a potential predicting factor for the occurrence of DCI.

A raising dawn of pentoxifylline in management of inflammatory disorders in Covid-19.

The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up-regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute lung injury and acute respiratory distress syndrome. Different repurposed had been in use in the management of Covid-19, one of these agents is pentoxifylline (PTX) which has anti-inflammatory and antioxidant properties. Therefore, the objective of the present mini-review is to highlight the potential role of PTX in Covid-19 regarding its anti-inflammatory and antioxidant effects. PTX is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate which stimulates protein kinase A and inhibits leukotriene and tumor necrosis factor. PTX has antiviral, anti-inflammatory and immunomodulatory effects, thus it may attenuate SARS-CoV-2-induced hyperinflammation and related complications. As well, PTX can reduce hyper-viscosity and coagulopathy in Covid-19 through increasing red blood cell deformability and inhibition of platelet aggregations. In conclusion, PTX is a non-selective phosphodiesterase drug, that has anti-inflammatory and antioxidant effects thereby can reduce SARS-CoV-2 infection-hyperinflammation and oxidative stress. Besides, PTX improves red blood cells (RBCs) deformability and reduces blood viscosity so can mitigate Covid-19-induced hyper-viscosity and RBCs hyper-aggregation which is linked with the development of coagulopathy. Taken together, PTX seems to be an effective agent against Covid-19 severity.

A New In Vitro Blood Hyperviscosity Model.

We developed a model of blood hyperviscosity avoiding extreme impact on the blood. The model shows reproducibility in rat blood under common storage conditions (4±1°C; stabilization with citrate-phosphate-glucose additive solution). Storage of rat blood under these condition leads to impairment of its rheological properties, which manifested in an increase in blood viscosity in a wide range of shear rates (3-300 sec-1). An increase in blood viscosity appeared the first day of storage and reached a maximum on the third day. During further 11-day storage, the blood viscosity did not change significantly. A hybrid macromolecular compound O-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoyl)-(1→6)-α-D-glucan improved the hemorheological properties during storage. The most pronounced effect was observed on the third day of storage and manifested in a decrease in blood viscosity in the range of shear rates of 50-300 sec-1. Thus, storage of rat blood with citrate-phosphate-glucose additive solution for 3 days at 4±1°C reproduces the phenomenon of blood hyperviscosity; this model can be used to screen agents with hemorheological activity.