Thrombogenic Potential Research Articles

Preclinical Evaluation of a New Anti-COVID-19 Intravenous Immunoglobulin

Introduction. Using of immunoglobulins containing SARS-CoV-2 neutralizing antibodies may be an effective and safe tool for COVID-19 treatment. An intravenous immunoglobulin COVID-globulin from donor blood plasma containing SARS-CoV-2 neutralizing antibodies was developed at Joint-Stock Company Nacimbio.Aim. A pilot study of the safety of the "COVID-globulin".Materials and methods. When studying the safety of the preparation in animals the following parameters were evaluated: general toxicity, thrombogenic potential, influence on hematological and biochemical parameters, blood clotting and hemolytic activity, determination of local irritant action, pyrogenic properties, bacterial endotoxins, allergic effect of the drug preparation and its physicochemical characteristics.Results and discussion. Safety studies of "COVID-globulin" in animals showed no signs of intoxication, local irritant action and thrombogenic properties. Macroscopic and histological examination of the organs of rats treated with COVID-globulin showed no signs of necrosis, inflammation, atypia, or any significant pathological changes. Hematological and biochemical parameters of the blood of laboratory animals after the administration of "COVID-globulin" corresponded to the reference values. Administration of COVID-globulin to rabbits did not activate blood clot formation. The IgG subclasses distribution in the preparation corresponded to that in human plasma. The activity of the Fc-function of the immunoglobulin molecule was more than 130 % compared to the reference standard preparation, the concentration of the prekallikrein activator in the COVID-globulin ranged from 4.2 to 4.8 IU/ml, anticomplementary activity was less than 1 unit complement per 1 mg of protein.Conclusion. The results of all studies have demonstrated a high level of safety of the developed COVID-globulin preparation, which meets the safety requirements for human immunoglobulins for intravenous administration by national regulatory documents and the European Pharmacopoeia.

Analysis of thrombosis risk of commissural misaligned transcatheter aortic valve prostheses using particle image velocimetry

Abstract Due to excellent clinical results, transcatheter aortic valve replacement (TAVR) has evolved to a treatment option for patients with low surgical risk, resulting in an increasing demand for durable heart valve prostheses. Durability of TAVR could be limited by leaflet thrombosis. Thrombus formation in the aortic root is mainly affected by the hemodynamic situation, which is dependent on the positioning of the implant. We investigated the flow field in the aortic root after TAVR implantation by means of particle image velocimetry. To quantify the influence of the implant-position with respect to an alignment or misalignment of the leaflet commissures on the thrombogenic potential, we used a transport equation for residence time (RT) to consider washout behavior. Furthermore, we introduced a shear effect criterion (SIE) to address platelet activation as a measure for a potential thrombus formation. Misaligned implantation of a TAVR resulted in a reversed direction of rotation of the occurring recirculation area. This led to fluid flow with comparable areas of increased relative blood RT (RTaligned: 97.6%, RTmisaligned: 88.0%) and a smaller area of low shear load for the misaligned TAVR (SIEaligned: 57.7%, SIEmisaligned: 3.70%) into the sinus region, indicating a higher potential for thrombus formation.

Effect of Temperature on Thrombogenicity Testing of Biomaterials in an In Vitro Dynamic Flow Loop System.

To develop and standardize a reliable in vitro dynamic thrombogenicity test protocol, the key test parameters that could impact thrombus formation need to be investigated and understood. In this study, we evaluated the effect of temperature on the thrombogenic responses (thrombus surface coverage, thrombus weight, and platelet count reduction) of various materials using an in vitro blood flow loop test system. Whole blood from live sheep and cow donors was used to assess four materials with varying thrombogenic potentials: negative-control polytetrafluoroethylene (PTFE), positive-control latex, silicone, and high-density polyethylene (HDPE). Blood, heparinized to a donor-specific concentration, was recirculated through a polyvinyl chloride tubing loop containing the test material at room temperature (22-24°C) for 1 hour, or at 37°C for 1 or 2 hours. The flow loop system could effectively differentiate a thrombogenic material (latex) from the other materials for both test temperatures and blood species ( p < 0.05). However, compared with 37°C, testing at room temperature appeared to have slightly better sensitivity in differentiating silicone (intermediate thrombogenic potential) from the relatively thromboresistant materials (PTFE and HDPE, p < 0.05). These data suggest that testing at room temperature may be a viable option for dynamic thrombogenicity assessment of biomaterials and medical devices.

Pleurotus eryngii Chips-Chemical Characterization and Nutritional Value of an Innovative Healthy Snack.

Nowadays, as the pandemic has reshaped snacking behaviors, and consumers have become more health-conscious, the need for the incorporation of "healthy snacking" in our diets has emerged. Although there is no agreed-upon definition of "healthy snacking", dietary guidelines refer to snack foods with high nutritional and biological value. The aim of this study was to chemically characterize and determine the nutritional value of an innovative UVB-irradiated and baked snack from Pleurotus eryngii mushrooms. P. eryngii is an edible mushroom native to the Mediterranean basin. We applied proximate composition, amino acids, fatty acids, vitamins, and macro and trace elements analyses. Also, we computed indices to assess the nutritional quality of food, and we evaluated the sensory characteristics of the mushroom snack. We found high nutritional, consumer, and biological values for the snack. More specifically it was low in calories, high in fibre and protein, low in lipids, without added sugars, and high in ergosterol and beta-glucans. Additionally, it had some vitamins and trace elements in significant quantities. Its NRF9.3 score was considerably high compared to most popular snacks, and the snack exhibited high hypocholesterolemic and low atherogenic and thrombogenic potentials. In conclusion, as a result of UVB-irradiation and baking of P. eryngii mushrooms, the snack's nutritional and biological value were not affected; instead, it provided a "healthy snacking" option.

Underlying mechanisms of thrombus formation/growth in atherothrombosis and deep vein thrombosis.

Thrombosis remains a leading cause of death worldwide despite technological advances in prevention, diagnosis, and treatment. The traditional view of arterial thrombus formation is that it is a platelet-dependent process, whereas that of venous thrombus formation is a coagulation-dependent process. Current pathological and basic studies on atherothrombosis and venous thrombosis have revealed the diverse participation of platelet and coagulation activation mechanisms in both thrombus initiation and growth processes during clinical thrombotic events. Atherosclerotic plaque cell-derived tissue factor contributes to fibrin formation and platelet aggregation. The degree of plaque disruption and a blood flow alteration promote atherothrombotic occlusion. While blood stasis/turbulent flow due to luminal stenosis itself initiates venous thrombus formation. The coagulation factor XI-driven propagation phase of blood coagulation plays a major role in venous thrombus growth, but a minor role in hemostasis. These lines of evidence indicate that atherothrombosis onset is affected by the thrombogenic potential of atherosclerotic plaques, the plaque disruption size, and an alteration in blood flow. Upon onset of venous thrombosis, enhancement of the propagation phase of blood coagulation under blood stasis and a hypercoagulable state contribute to large thrombus formation.

The impact of rotor configurations on hemodynamic features, hemocompatibility and dynamic balance of the centrifugal blood pump: A numerical study.

To investigate the effect of rotor design configuration on hemodynamic features, hemocompatibility and dynamic balance of blood pumps. Computational fluid dynamics was employed to investigate the effects of rotor type (closed impeller, semi-open impeller), clearance height and back vanes on blood pump performance. In particular, the Eulerian hemolysis model based on a power-law function and the Lagrangian thrombus model with integrated stress accumulation and residence time were applied to evaluate the hemocompatibility of the blood pump. This study shows that compared to the closed impeller, the semi-open impeller can improve hemolysis at a slight sacrifice in head pressure, but increase the risk of thrombogenic potential and disrupt rotor dynamic balance. For the semi-open impeller, the pressure head, hemolysis, and axial thrust of the blood pump decrease with increasing front clearance, and the risk of thrombosis increases first and then decreases with increasing front clearance. Variations in back clearance have little effect on pressure head, but larger on back clearance, worsens hemolysis, thrombogenic potential and rotor dynamic balance. The employment of back vanes has little effect on the pressure head. All back vanes configurations have an increased risk of hemolysis in the blood pump but are beneficial for the improvement of the rotor dynamic balance of the blood pump. Reasonable back vanes configuration (higher height, wider width, longer length and more number) decreases the flow separation, increases the velocity of blood in the back clearance, and reduces the risk of blood pooling and thrombosis. It was also found that hemolysis index (HI) was highly negatively correlated with pressure difference between the top and back clearances (r=-.87), and thrombogenic potential was positively correlated with pressure difference between the top and back clearances (r=.71). This study found that rotor type, clearance height, and back vanes significantly affect the hydraulic performance, hemocompatibility and rotor dynamic balance of centrifugal blood pumps through secondary flow. These parameters should be carefully selected when designing and optimizing centrifugal blood pumps for improving the blood pump clinical outcomes.

Hypercoagulability and Thrombosis Risk in Prostate Cancer: The Role of Thromboelastography.

Thrombosis is one of the leading causes of death in cancer. Cancer-induced hypercoagulable state contributes to thrombosis and is often overlooked. Prostate cancer may not be of high thrombogenic potential compared with other cancers, but its high prevalence brings it into focus. Pathological evidence for venous thromboembolisms (VTEs) in prostate cancer exists. Factors such as age, comorbidities, and therapies increase the VTE risk further. There is a need to systematically identify the risk of VTE in regard to patient-, cancer-, and treatment-related factors to risk stratify patients for better-targeted and individualized strategies to prevent VTE. Sensitive tests to enable such risk assessment are urgently required. There is sufficient evidence for the utility of thromboelastography (TEG) in cancer, but it is not yet part of the clinic and there is only limited data on the use of TEG in prostate cancer. One study revealed that compared with age-matched controls, 68.8% of prostate cancer patients demonstrated hypercoagulable TEG parameters. The absence of clinical guidelines is a limiting factor in TEG use in the cancer population. Cancer heterogeneity and the unique cancer-specific microenvironment in each patient, as well as determining the hypercoagulable state in each patient, are added limitations. The way forward is to combine efforts to design large multicenter studies to investigate the utility and clinical effectiveness of TEG in cancer and establish longitudinal studies to understand the link between hypercoagulable state and development of thrombosis. There is also a need to study low thrombogenic cancers as well as high thrombogenic ones. Awareness among clinicians and understanding of test applicability and interpretation are needed. Finally, expert discussion is critical to identify the investigation priorities.

Optimizing the Porohyperelastic Response of a Layered Compliance Matched Vascular Graft to Promote Luminal Self-Cleaning.

Thrombosis and intimal hyperplasia have remained the major failure mechanisms of small-diameter vascular grafts used in bypass procedures. While most efforts to reduce thrombogenicity have used a biochemical surface modification approach, the use of local mechanical phenomena to aid in this goal has received somewhat less attention. In this work, the mechanical, fluid transport, and geometrical properties of a layered and porous vascular graft are optimized within a porohyperelastic finite element framework to maximize self-cleaning via luminal reversal fluid velocity (into the lumen). This is expected to repel platelets as well as inhibit the formation of and/or destabilize adsorbed protein layers thereby reducing thrombogenic potential. A particle swarm optimization algorithm was utilized to maximize luminal reversal fluid velocity while also compliance matching our graft to a target artery (rat aorta). The maximum achievable luminal reversal fluid velocity was approximately 246 μm/s without simultaneously optimizing for host compliance. Simultaneous optimization of reversal flow and compliance resulted in a luminal reversal fluid velocity of 59 μm/s. Results indicate that a thick highly permeable compressible inner layer and a thin low permeability incompressible outer layer promote intraluminal reversal fluid velocity. Future research is needed to determine the feasibility of fabricating such a layered and optimized graft and verify its ability to improve hemocompatibility.

Recommendations for the Development of CFD Model to Assess the Thrombogenic Potential of Stents

Abstract Computational fluid dynamics (CFD) has enormous potential for the development of novel cardiovascular implants. In particular, the evaluation of the thrombogenic potential of implants is gaining importance. For this purpose, the numerical model must represent the essential properties of the real system, i.e., an implant in the human blood circulation, in a suitable form. Due to its complexity, the model building process is crucial for the successful application of the model. Currently, there is no structured guideline for the application of numerical flow simulation to which model developers can refer. Based on NASA and ASTM, we present key aspects of the model building process using CFD for stent flow as an example.

Impact of volute design features on hemodynamic performance and hemocompatibility of centrifugal blood pumps used in ECMO.

The centrifugal blood pump volute has a significant impact on its hemodynamic performance hemocompatibility. Previous studies about the effect of volute design features on the performance of blood pumps are relatively few. In the present study, the computational fluid dynamics (CFD) method was utilized to evaluate the impact of volute design factors, including spiral start position, volute tongue radius, inlet height, size, shape and diffuser pipe angle on the hemolysis index and thrombogenic potential of the centrifugal blood pump. Correlation analysis shows that flow losses affect the hemocompatibility of the blood pump by influencing shear stress and residence time. The closer the spiral start position of the volute, the better the hydraulic performance and hemocompatibility of the blood pump. Too large or too small volute inlet heights can worsen hydraulic performance and hemolysis, and higher volute inlet height can increase the thrombogenic potential. Small volute sizes exacerbate hemolysis and large volute sizes increase the thrombogenic risk, but volute size does not affect hydraulic performance. When the diffuser pipe is tangent to the base circle of the volute, the best hydraulic performance and hemolysis performance of the blood pump is achieved, but the thrombogenic potential is increased. The trapezoid volute has poor hydraulic performance and hemocompatibility. The round volute has the best hydraulic and hemolysis performance, but the thrombogenic potential is higher than that of the rectangle volute. This study found that the hemolysis index shows a significant correlation with spiral start position, volute size, and diffuser pipe angle. Thrombogenic potential exhibits a good correlation with all the studied volute design features. The flow losses affect the hemocompatibility of the blood pump by influencing shear stress and residence time. The finding of this study can be used to guide the optimization of blood pump for improving the hemodynamic performance and hemocompatibility.

Abstract 3849: Exosomes in polycythemia vera: "mini platelets" with oncogenic and thrombogenic potential

Abstract Polycythemia vera (PV) is a classical "myeloproliferative neoplasm" characterized by clonal proliferation of myeloid progenitor cells caused by their acquisition of a mutation in the JAK2 gene. Its common complications are thrombosis and second primary malignancies. Secreted from virtually all cell types, exosomes are extracellular vesicles that carry bioactive cargo derived from their cells of origin. When engulfed, their cargo may alter the phenotype of the recipient cells. For example, neoplastic exosomes modulate the cellular makeup of bystander cells. Therefore, since mutated JAK2 is present in virtually all PV-patients, we hypothesize that PV-derived exosomes (hereafter PV-exo) carry the mutated JAK2 oncogene and are taken up by non-clonal cells, thus contributing to the thrombotic manifestations and oncogenic potential of patients with PV. We isolated and characterized exosomes from PV-patients and from the Human erythroleukemia (HEL) cell line (hereafter HEL-exo). We exposed normal cells implicated in thrombosis and skin cells to these exosomes and examined the cells' phenotypic changes and activation after exposure. Using Sanger sequencing we discovered that both PV-exo and HEL-exo, like their parental cells, carry the mutated JAK2 transcripts, allowing clonal cells to export oncogenes to distant, non-clonal sites. Our preliminary findings suggest that these exosomes promote pro-coagulant and malignant phenotypes in multiple ways. Thrombin generation assay pointed to a significantly higher generation of thrombin in the presence of PV-exo than those derived from healthy donors. Similarly, flow cytometry analysis revealed that PV-exo increased the expression of platelet activation markers. Moreover, Trans Endothelial Electrical Resistance (TEER) assay results suggest that HEL-exo induces endothelial dysfunction. Furthermore, using the Sulforhodamine B assay, we found that exposure to HEL-exo increased the proliferation of normal keratinocytes. In summary, we developed the concept of exosomes as “mini metastasis” that might promote disease manifestations either directly or indirectly. Since unlike solid tumors, hematological malignancies do not metastasize, exosomes derived from neoplastic hematological cells may fulfill this function. Such exosomes may spread oncogenes (e.g., mutated JAK2), damage non-clonal tissues (e.g., endothelial dysfunction) or act as a miniature reflection of their cells of origin (e.g., exosomes as mini platelets) in a parallel way to "real" metastasis; this concept may affect treatment related decisions. For example, by reducing clonal burden, early treatment even in “low risk” patients may prevent exosomal spread and exosomal-dependent damage to distant tissues. The results of our study highlight PV-exo as promoters of PV-complications, thrombosis and malignant transformation. Citation Format: Orit Uziel, Adi Shacham-Abulafia, Galia Spectre, Ester Ziv, Karyn Revital Geiger, Zinab Sarsor, Neria Ron, Einat Beery, Pia Raanani, Shoshana Revel-Vilk, Mira Naamad, Uri Rozovski. Exosomes in polycythemia vera: "mini platelets" with oncogenic and thrombogenic potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3849.

P12: Investigation of Ventricular Assist Device Inflow Configurations Within Single Ventricle Hearts

Study: Ventricular assist devices (VADs) provide cardiac support to failing hearts. A recent study showed that over half of VAD inflow cannulas are malpositioned; this number is estimated to be greater in patients with congenital heart defects. VAD malpositioning can lead to thrombus formation (clotting), pump failure, or even patient death. The relationship between VAD inflow cannula configuration and thrombus formation was explored for a pediatric patient with a single systemic ventricle. Methods: A post-Fontan hypoplastic left heart syndrome pediatric patient was evaluated. Computational fluid dynamics (CFD) was used to investigate the potential for thrombus formation in the apical vs. diaphragmatic inflow cannula configurations. A dynamic, non-Newtonian Carreau model was used and thrombogenic potential was defined by fluid with low velocity, low strain, and long residence times. CFD was validated using particle image velocimetry (PIV) and a mock circulatory loop with a moving ventricular sac. Results: While regions with thrombogenic potential were found in both the diaphragmatic and apical cannula configurations, the apical position exhibited a greater volume of fluid with these characteristics. PIV also confirmed these results. Conclusions: Although low velocity, low strain, long residence time flow may be indicative of thrombogenic potential, many factors actually contribute to thrombus formation and should be taken into account when comparing VAD implant configurations. Furthermore, while PIV validated overall trends observed in CFD, specific numerical values differed, suggesting the need for future refinement of both the CFD and PIV models.

237-OR: Platelet-Derived Protein Responses Differ According to Severity of Hypoglycemia

Introduction: Severe hypoglycemia is associated with an increased risk of cardiovascular (CV) death, and platelet responses to hypoglycemia (hypo) have been described. The impact of a transient severe hypo versus prolonged less severe hypo is unclear. Methods: 2 hypo studies were compared; firstly, in 18 subjects (type 2 diabetes (T2D) : 8 controls) blood glucose lowered to 3.5mmoL/L (90mg/dL) for 1-hour; secondly, in 46 subjects (23 T2D: 23 controls) blood glucose lowered to &amp;lt;2.2mmoL/L (&amp;lt;40mg/dL) transiently. The platelet-related protein (PRP) responses from baseline to after 1-hour of hypo (study-1) or at severe transient hypo (study-2) were compared, and at 24-hours post-hypo. Slow Off-rate Modified Aptamer (SOMA) -scan plasma protein measurement was used to determine platelet-related protein changes for 13 proteins. Results: In T2D, from baseline to hypo, differences were seen for 4 PRPs, three showing increased percent change in study-2 (plasminogen activator inhibitor-1 (PAI-1) , platelet glycoprotein VI (PGVI) and Tissue factor) , one showing increased percent change in study-1 (CD40 ligand (CD40LG)) ; at 24-hours in T2D, percent change for CD40LG remained increased, together with von Willebrand factor (vWF) , in study-2. In controls, from baseline to hypo, differences were seen for four PRPs, three showing increased percent change in study-2 (PAI-1, CD40LG and Protein S) , one showing increased percent change in study-1 (vWF) ; at 24-hours in controls, percent change for Protein S remained increased in study-2, whilst percent change for vWF and plasminogen were increased in study-1. Conclusion: Thrombogenic potential was enhanced in T2D versus controls, as evidenced by an increased thrombogenic protein expression profile in both mild and severe hypoglycemia, that showed persistent changes at 24-hours in severe hypo. Disclosure A. Moin: None. H. Kahal: None.

Prospective directions for creating a strategy for effective medicine prevention of preeclampsia (Literature review)

Preeclampsia (PE) is a main cause of morbidity and mortality for both mother and fetus. The frequency of PE is from 2 % to 8 %. The complications which are related to PE lead to more than 50,000 maternal deaths and more than 500,000 fetal deaths worldwide each year. In Ukraine, PE was diagnosed in 11,075 women in 2020 (39.32 per 1,000 births), of which severe PE was diagnosed in 1,573 women (5.58 per 1,000 births).The advances in obstetrics and neonatology have significantly mitigated many adverse pregnancy outcomes associated with PE. The optimal prevention of PE is essential to prevent the morbidity and mortality associated with this pathology. The number of researches about new management for the prevention or treatment of PE and new drugs that can affect the pathophysiology of the disease increases. The main value of potential candidates for the prevention of PE is the preclinical impact on oxidative stress, antiangiogenic factors, as well as thrombogenic potential and proinflammatory pathways of pathology development. A systematic data search was carried out in MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar and Proquest databases for 2014–2022. In this review, the results of preclinical and clinical studies about the rational prevention of the development of PE in pregnant women at risk with the involvement of the most promising drugs were analyzed. Preclinical studies have suggested new molecular targeting strategies, such as monoclonal antibodies directed against tumor necrosis factor alpha, placental growth factor, and short interfering ribonucleic acid technology to inhibit soluble fms-like tyrosine kinase-1 or angiotensinogen gene expression. Other treatment approaches that have progressed to phase III trials (either completed or ongoing) include proton pump inhibitors, metformin, nitric oxide donors and precursors, recombinant antithrombin III, digoxin immune antigen, and melatonin. There are cases suggesting that deletion of circulating soluble fms-like tyrosine kinase-1 can help to stabilize PE and prolong pregnancy.

A New Mathematical Numerical Model to Evaluate the Risk of Thrombosis in Three Clinical Ventricular Assist Devices

(1) Background: Thrombosis is the main complication in patients supported with ventricular assist devices (VAD). Models that accurately predict the risk of thrombus formation in VADs are still lacking. When VADs are clinically assisted, their complex geometric configuration and high rotating speed inevitably generate complex flow fields and high shear stress. These non-physiological factors can damage blood cells and proteins, release coagulant factors and trigger thrombosis. In this study, a more accurate model for thrombus assessment was constructed by integrating parameters such as shear stress, residence time and coagulant factors, so as to accurately assess the probability of thrombosis in three clinical VADs. (2) Methods: A mathematical model was constructed to assess platelet activation and thrombosis within VADs. By solving the transport equation, the influence of various factors such as shear stress, residence time and coagulation factors on platelet activation was considered. The diffusion equation was applied to determine the role of activated platelets and substance deposition on thrombus formation. The momentum equation was introduced to describe the obstruction to blood flow when thrombus is formed, and finally a more comprehensive and accurate model for thrombus assessment in patients with VAD was obtained. Numerical simulations of three clinically VADs (CH-VAD, HVAD and HMII) were performed using this model. The simulation results were compared with experimental data on platelet activation caused by the three VADs. The simulated thrombogenic potential in different regions of MHII was compared with the frequency of thrombosis occurring in the regions in clinic. The regions of high thrombotic risk for HVAD and HMII observed in experiments were compared with the regions predicted by simulation. (3) Results: It was found that the percentage of activated platelets within the VAD obtained by solving the thrombosis model developed in this study was in high agreement with the experimental data (r² = 0.984), the likelihood of thrombosis in the regions of the simulation showed excellent correlation with the clinical statistics (r² = 0.994), and the regions of high thrombotic risk predicted by the simulation were consistent with the experimental results. Further study revealed that the three clinical VADs (CH-VAD, HVAD and HMII) were prone to thrombus formation in the inner side of the secondary flow passage, the clearance between cone and impeller, and the corner region of the inlet pipe, respectively. The risk of platelet activation and thrombus formation for the three VADs was low to high for CH-VAD, HVAD, and HM II, respectively. (4) Conclusions: In this study, a more comprehensive and accurate thrombosis model was constructed by combining parameters such as shear stress, residence time, and coagulation factors. Simulation results of thrombotic risk received with this model showed excellent correlation with experimental and clinical data. It is important for determining the degree of platelet activation in VAD and identifying regions prone to thrombus formation, as well as guiding the optimal design of VAD and clinical treatment.

A new way to evaluate thrombotic risk in failure heart and ventricular assist devices

Thrombosis is one of the main complications in patients implanted with ventricular assist device (VAD). The complicated structure and disturbed flow field within failure heart and blood pump play an important role in thrombosis formation. In this study, the influence of Left ventricular (LV) volumes on flow field contributing to thrombosis formation within failure heart and VAD was investigated. Computational Fluid Dynamics (CFD) methods were employed to investigate the effect of different LV volumes on the thrombogenic potential of failure heart and VAD. Lagrangian methods were utilized to obtain information on platelet voyage trajectories. The concepts of mean and threshold of stress accumulation and residence time were introduced to accurately assess the likelihood of thrombus. Eulerian methods were used to identify thrombus-prone locations. CFD results showed that residence time (RT) was the main cause of thrombus formation in the failure heart, and the percentage of platelet trajectories above the RT threshold increased significantly with increasing LV volume. The RT in the left atrial appendage and LV increased significantly with LV volume increasing, which indicated that thrombus is prone to form there. Compared with the failure heart, non-physiological shear stress (NPSS)-caused platelet activation is the main reason for thrombus formation within VAD. The narrow zones (top clearance and secondary flow passage) within VAD have a high incidence of thrombus generation. In VAD patients, the LV volume has an important impact on thrombosis probability within failure heart, in which the larger size of the LV volume is, the higher risk of thrombosis will be. The size of LV volume has little effect on the thrombosis formation probability of VAD, where the NPSS plays the leading role in thrombosis formation. The finding of this study can be utilized to guild the clinical treatment and VAD structure optimization design for reducing the thrombosis risk.

Association between COVID-19 Diagnosis and Coronary Artery Thrombosis: A Narrative Review.

Coronavirus disease 2019 is characterized by its severe respiratory effects. Data early on indicated an increased risk of mortality in patients with cardiovascular comorbidities. Early reports highlighted the multisystem inflammatory syndrome, cytokine storm, and thromboembolic events as part of the disease processes. The aim of this review is to assess the association between COVID-19 and its thrombotic complications, specifically related to the cardiovascular system. The role of neutrophil extracellular traps (NETs) is explored in the pathogenesis of the disease. The structure and anatomy of the virus are pivotal to its virulence in comparison to other α and β Coronaviridae (HCoV-229E, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1). In particular, the host interaction and response may explain the variability of severity in patients. Angio tensin-converting enzyme 2 (ACE2) activation may be implicated in the cardiovascular and throm bogenic potential of the disease. The virus may also have direct effects on the endothelial lining affecting hemostasis and resulting in thrombosis through several mechanisms. Dipyridamole may have a therapeutic benefit in NET suppression. Therapeutic avenues should be concentrated on the different pathophysiological steps involving the virus and the host.

In Vitro Studies Regarding the Safety of Chitosan and Hyaluronic Acid-Based Nanohydrogels Containing Contrast Agents for Magnetic Resonance Imaging.

The aim of this study was to investigate the biocompatibility of contrast agents, such as gadolinium 1, 4, 7, 10 tetraazacyclo-dodecane tetraacetic acid (GdDOTA) and gadolinium dioctyl terephthalate (GdDOTP), encapsulated in a polymeric matrix containing chitosan and hyaluronic acid using RAW264.7 murine macrophages and human blood samples. The cell viability and cytotoxicity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, while cell cycle analysis was determined in RAW264.7 cells using flow cytometry. The mitochondrial membrane potential (MMP), hemolytic index, complement activation, and thrombogenic potential of gadolinium (Gd) containing nanohydrogels were measured by fluorometric and spectrophotometric methods. Taken together, our results demonstrate the good bio- and hemocompatibility of chitosan-based nanohydrogels with the RAW264.7 cell line and human blood cells, suggesting that these could be used as injectable formulations for the magnetic resonance imaging diagnostic of lymph nodes.

Development of DVT in an operated case of cemented bipolar hemiarthroplasty during COVID pandemic: a case report

&lt;p class="abstract"&gt;One of the most common treatment for fracture neck of femur in the elderly is bipolar hemi-arthroplasty which is associated with the patient being mobilized early, lower complication rate, longer implant life. Both uncemented and cemented arthroplasty have been associated with good outcomes, however cemented arthroplasty has higher incidences of DVT due to the thrombogenic potential of cement in addition to the hypercoagulability due to the femoral fracture. Hence, DVT remains a life-threatening complication of arthroplasty, despite the preventive measures owing also to certain genetic and acquired risk factors. We have a 70-year-old female patient, who presented to us with a post traumatic right sided displaced neck of femur with greater trochanter fracture following an alleged history of slip and fall at home who was operated with cemented bipolar hemi-arthroplasty. The patient developed deep vein thrombosis of the operated limb even after adequate mobilization with full weight bearing over the operated limb from post op day 2 and other adequate physiotherapy exercises such as hip/knee ROM exercises and ankle pump exercises. Although, our case report seems to be too far-fetched in terms of correlating this episode of DVT even after adequate mobilization from POD-2 to the ongoing COVID-19 pandemic causing a sub-clinical asymptomatic coronavirus infection causing an increased hypercoagulability of the blood as has been demonstrated by various studies, it does provide substantial evidence which warrants wider multi-centric studies in order to provide a definite correlation of the aforementioned scenario. &lt;/p&gt;

An Optimized Purification Design for Extracting Active ADAMTS13 from Conditioned Media

ADAMTS13 is a hemostatic enzyme that breaks down pro-thrombotic ultra-large multimers of von Willebrand factor (VWF). The deficiency of ADAMTS13 increases VWF-mediated thrombogenic potential and may lead to thrombotic thrombocytopenic purpura (TTP). Recently, clinical studies have shown the development of acquired TTP after COVID-19 infection and a correlation between low ADAMTS13 plasma levels and increased mortality. As a result, investigating ADAMTS13 as a potential recombinant therapeutic is of broad interest in the field of hematology. ADAMTS13 is considered challenging to purify in its biologically active state. Current purification methods utilize immobilized metal ions, which can interfere with ADAMTS13 metalloprotease activity. For this reason, we optimized an alternative strategy to isolate milligram quantities of highly active recombinant ADAMTS13 (rADAMTS13) from conditioned media after exogenous expression in human cell line, HEK293. HEK293 cells stably expressing C-terminal V5-His-tagged ADAMTS13 were grown in two parallel systems, culture bottles and flasks, for identifying an optimal cultivation strategy. Subsequently, we employed anion exchange followed by anti-V5-tag affinity chromatography to purify rADAMTS13, and extracted rADAMTS13 of high specific activity while preserving its native post-translational modifications. In addition, this process has been optimized and scaled up to produce active rADAMTS13 at levels sufficient for laboratory-scale structural, enzymatic, and biochemical studies.