Platelet Density Research Articles

Abstract 2273: Development of a prognostic biomarker for ovarian cancer based on a high-resolution digital pathology platform for spatial statistical analysis of platelets and blood vessels

Abstract Purpose: A third of ovarian cancer patients have elevated platelet counts that are associated with poor prognosis. However, the exact mechanism by which platelets preferentially extravasate into tumor microenvironment is unknown, partly owing to lack of effective tools that can accurately segment and measure platelet counts found in tumor tissues. In this study, we developed a high-resolution digital pathology (DP) platform with whole tissue confocal imaging and deep learning model that can be used to automatically segment out platelets and blood vessels to perform spatial statistics (SA) of platelets with high precision and consistency. We utilized our SADP platform to study an interaction between tumor secreted SDF-1 and CXCR4 on platelets which initiates platelet chemotaxis towards tumor microenvironment. Methods: A deep learning algorithm to accurately segment out platelets was developed based on the U-Net structure using our original datasets from the murine ovarian cancer model. Tumor-bearing mice were injected with 5 mg/kg of Plerixafor, a CXCR4 inhibitor, daily for 4 weeks. Then, tumor nodules were resected, stained with CD41a and CD31 antibodies, and imaged using a whole slide confocal microscopy. We performed manual annotation of these images to generate the mask dataset and performed further data augmentation to increase the diversity of datasets. We trained our model using 85% of these images and performed validation using the remaining 15%. Results: Using our SADP platform, the validation dataset achieved pixel-wise accuracy of 98.8%. A receiver operating characteristic (ROC) curve demonstrated an area under the ROC curve (AUC) of 0.99 with high sensitivity and specificity. Intersection over union (IoU) score of 0.765 was obtained. A statistically significant (p=0.0467), 7.03% reduction in the platelet density was shown in the Plerixafor-treated mouse ovarian tumor tissues (n=8) compared to the control tumor tissues (n=9). We also found that platelets are spatially concentrated near blood vessels in the control tumor tissues compared to the Plerixafor-treated tumor tissues (p=0.0377). Conclusions: We developed a SADP platform to segment and quantitate tens of thousands of platelets from whole slide mouse ovarian cancer tissues automatically with high accuracy and consistency and incorporated spatial statistics to understand their spatial relationships and patterns that would not be apparent in non-spatial analyses. Applying the SADP platform, we demonstrated that treatment with Plerixafor leads to overall reduction in platelet infiltration within ovarian murine tumors. Our ongoing effort is to utilize our SADP platform on human tumor tissue images from a whole slide digital scanner to further characterize spatial distribution of platelets as a potential prognostic marker for ovarian cancer. Citation Format: Ju Young Ahn, Wendolyn Carlos-Alcalde, Matthew Vasquez, Min Soon Cho, Vahid Afshar-Kharghan, Stephen T. Wong. Development of a prognostic biomarker for ovarian cancer based on a high-resolution digital pathology platform for spatial statistical analysis of platelets and blood vessels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2273.

Enhancing Titanium Disk Performance through In-Pack Cold Atmospheric Plasma Treatment.

While titanium dental implants have already been clinically established, ongoing research is continuously being conducted to advance the fields of osseointegration and bacterial resistance, seeking further improvements in these areas. In this study, we introduce an innovative method for treating titanium surfaces within tightly sealed packaging. Specifically, titanium discs, enclosed in surgical-grade packaging, underwent treatment using cold atmospheric plasma (CAP). The surfaces were thoroughly characterized in terms of wettability, crystalline structure, and chemical composition. Hemocompatibility analyses were conducted using blood diluted in sodium citrate (1:9) exposed to titanium discs for 30 min inside a CO2 incubator at 37 °C. Subsequently, various blood parameters were evaluated, including prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet adhesion. Microbiological analyses were also performed using Pseudomonas aeruginosa (ATCC 27853) for 4 h at 37 °C. The treatment with CAP Jet resulted in a reduction in contact angle without causing any changes in the crystalline structure. No statistically significant differences were observed in the blood parameters. The plasma-treated samples exhibited lower PT and APTT values compared to those of the control group. The surfaces treated with CAP Jet showed increased platelet activation, platelet density, and thrombus formation when compared with the untreated samples. Moreover, the treated surfaces demonstrated lower bacterial colony formation compared with other surfaces.

Fibrin Network and Platelets Densities in Platelet-Rich Fibrin (PRF) Membranes Produced from Plastic Tubes Without Additives: A New Approach to PRF Clinical Use.

The present study aimed to investigate plastic tubes without additives as alternatives to glass and silica-coated plastic tubes, in the production of PRF membranes. Nine blood samples were collected from eight volunteers (n = 8) separated into three groups, according to tube material: glass, silica-coated plastic, and plastic without additives. In each group, the samples were centrifuged using different relative centrifugation forces: L-PRF (700g/12min), A-PRF (200g/14min), and A-PRF + (200g/8min). The generated membranes were evaluated by histomorphometry, considering the fibrin network, platelet aggregates, and cellular morphology, by light microscopy. The ultrastructural cellular morphology integrity was evaluated by transmission electron microscopy. The L-PRF (p < 0.019) and A-PRF (p < 0.001) membranes showed a significantly lower fibrin network density in plastic tubes without additives compared to glass and silica-coated plastic tubes. Plastic tubes without additives revealed a significantly higher platelet percentage, regardless of the protocol (p < 0.005). In all groups, TEM analysis showed preserved normal morphological ultrastructure, maintaining the integrity of cellular components. Plastic tubes without additives offer a viable alternative for producing PRF membranes. They exhibited a higher platelet density and demonstrated fibrin network and cellular morphology similar to those of glass and silica-coated plastic tubes, irrespective of the centrifugation protocol.

Effect of EDTA Activation on Blood Clot Structure in Regenerative Endodontics: A Scanning Electron Microscopy Study

IntroductionEDTA plays a crucial role in regenerative endodontic therapy (RET) because of its significant biological effects. However, EDTA is also recognized as the preferred anticoagulant for hematologic tests. Thus, this study aimed to assess the influence of different EDTA activation techniques on the morphology of blood clots after conditioning the root canal dentin. MethodsForty extracted human teeth were prepared to simulate immature teeth and divided into the following 5 groups: (1) saline solution (negative control), (2) EDTA 17% + saline solution (CNI), (3) CNI + ultrasonic activation, (4) CNI + Easy clean activation, and (5) CNI + XP-endo Finisher activation. After irrigation, the roots were cleaved, and the root canals were filled with human blood to clot formation. The morphology and density of erythrocytes, platelets, and the fibrin network were observed using a scanning electron microscope. The fibrin network density was classified using a 4-point scale. Data were analyzed using the Friedman test and the Kruskal-Wallis test with Bonferroni adjustment (α = 5%). ResultsAll groups exhibited consistent blood clot morphology characterized by a high density of erythrocytes, platelets, and white blood cells throughout the entire length of the root canal. The negative control group showed statistically significant high scores of fibrin density compared with the CNI group in all root thirds (P < .05). However, there was no statistical difference in the scores for the fibrin network density between the groups irrigated with EDTA with and without activation (P > .05). ConclusionsEDTA may impair the fibrin network formation compared with the saline group. However, EDTA activation did not significantly change the effects on the blood clot in contact with the conditioned intraradicular dentin.

Effect of Atomic-Layer-Deposited Hydroxyapatite Coating on Surface Thrombogenicity of Titanium

This study aimed to evaluate the surface characteristics of a nanocrystalline hydroxyapatite coating made through atomic layer deposition (ALD-HA) on titanium surfaces and to investigate its effect on blood coagulation and platelet adhesion. Grade 2 square titanium discs (0.7 cm, 1 mm thick) were used (n = 108). Half of the substrates (n = 54) were coated with ALD-HA, and the other half were used as the non-coated control. Surface free energy (SFE), contact angle (CA), surface roughness (Ra), and chemical composition were evaluated. Blood thrombogenic properties were assessed on ALD-HA and non-coated surfaces using the kinetic clotting time method. The platelets’ adhesion and morphology were also evaluated. The ALD-HA-coated surfaces demonstrated significantly higher polar SFE (p &lt; 0.001) and lower CA (p &lt; 0.001) values compared to the non-coated surfaces. In addition, the surface roughness was significantly lower for the ALD-HA (p &lt; 0.001) than for the non-coated surfaces. Platelets adhered to both surfaces; however, there was variability in platelet morphologies in different areas with higher platelet density on the ALD-HA surfaces. There was no significant difference in the overall absorbance values of the hemolyzed hemoglobin for both substrates, and the total clotting time was achieved at 60 min. It can be concluded that the ALD-HA coating of titanium can enhance surface wettability, increase surface free energy, and support blood coagulation and platelet adhesion.

Abstract 5406: A deep learning enabled digital pathology platform for characterization of cancer-associated thrombosis of ovarian cancer

Abstract Purpose: Cancer-associated thrombosis (CAT), characterized by activation, extravasation, and aggregation of platelets in tumor microenvironment, is a common complication observed in ovarian cancer patients. A third of ovarian cancer patients have elevated platelet counts that are associated with poor prognosis. However, the exact mechanism by which platelets preferentially extravasate into tumor microenvironment is unknown, partly owing to lack of tools that can accurately segment and measure platelet counts found in tumor tissues. In this study, we hypothesize that tumor secreted SDF-1 interacts with CXCR4 receptors on platelets and initiates platelet chemotaxis towards tumor microenvironment. We developed a digital pathology (DP) platform with automated whole tissue confocal imaging and deep learning (DL) model that can be used to automatically segment out platelets and calculate platelet density with high precision and consistency in the mouse ovarian cancer tissue sections for supporting hypothesis evaluation. Methods: A DL algorithm to accurately segment out platelets was developed based on the U-Net structure using our original datasets from the murine ovarian cancer model. Tumor-bearing mice were injected with 5 mg/kg of Plerixafor, a CXCR4 inhibitor, daily for 4 weeks. Then, tumor nodules were resected, stained with CD41a antibody, and imaged using the whole slide confocal microscopy. Using these high-resolution images, we performed manual annotation of platelets to generate the mask dataset and performed further data augmentation to increase the diversity of datasets. We trained our model using 85% of these images and performed validation using the remaining 15%. Results: Using our DLDP platform, the validation dataset achieved pixel-wise accuracy of 98.7%. A receiver operating characteristic (ROC) curve demonstrated an area under the ROC curve (AUC) of 0.99 with high sensitivity and specificity. Intersection over union (IoU) score of 0.724 was obtained. A statistically significant (p=0.0467), 7.03% reduction in the platelet density was shown in the Plerixafor-treated mouse ovarian tumor tissues (n=8) compared to the control tumor tissues (n=9). Note that the traditional threshold method was not able to find the statistical significance (p=0.0966) in the same dataset. Conclusions: We developed a DLDP platform to segment and quantitate tens of thousands of platelets from whole slide mouse ovarian cancer tissues automatically with high accuracy and consistency. Applying the DLDP platform, we demonstrated that treatment with Plerixafor leads to overall reduction in platelet infiltration within ovarian murine tumors. With high-throughput, accurate, and automated detection of platelets, our DLDP platform can serve as a powerful tool for characterization of CAT by evaluation of platelet density as a potential prognostic biomarker for ovarian cancer. Citation Format: Ju Young Ahn, Wendolyn Carlos-Alcalde, Matthew Vasquez, Min Soon Cho, Vahid Afshar-Kharghan, Stephen T. Wong. A deep learning enabled digital pathology platform for characterization of cancer-associated thrombosis of ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5406.

Diabetes type 2: relationships between lysosomal exocytosis of circulating normal-sized platelets and in vitro ɑ-thrombin-evoked platelet responses

Background/objective Type 2 diabetes is a major risk factor for atherosclerotic disease. It is well agreed that the reactivity of diabetic platelets is increased but how platelet reactivity regulates is unknown. In our laboratory, density separated platelets have been investigated extensively and high- and low-density platelets circulate in an activated state. The density distribution of circulating platelets is altered in diabetes type 2 as well. We hypothesize that such platelets modify whole blood (WB) in vitro α-thrombin-evoked (10 μM/mL) activity in type 2 diabetes. Thus, the study aims to identify features of circulating normal-sized density subpopulations affecting whole blood (WB) platelet reactivity in type 2 diabetes. Patients and methods Patients with type 2 diabetes (n = 16) were enrolled. Their normal-sized platelets were divided into density subfractions (n = 16) using continuous polyvinylpyrrolidone-coated silica (Percoll™) gradients (density span, 1.090–1.040 kg/L) containing prostaglandin E1. The proportions (%) of such density-separated platelets expressing lysosomal-associated membrane protein 1 (LAMP-1) were analyzed using a flow cytometer. Further, determinations of WB ɑ-thrombin-evoked (10 U/mL) surface LAMP-1 (an assessment of lysosomal release), the fibrinogen (αIIbβ3) receptor activity, annexin V (binds to exposed membrane phosphatidylserine), and mitochondrial transmembrane potentials (an estimate of organelle integrity) were performed. Surface LAMP-1 expressions of individual normal-sized platelet density subpopulations were stratified into equal-sized groups (n = 2) depending on reactivity, as judged from the ɑ-thrombin-induced WB activity markers. Results With some exceptions, the proportion of normal-sized circulating platelets showing spontaneous LAMP-1 was strongly associated with WB ɑ-thrombin-evoked (10 U/mL) surface LAMP-1 and αIIbβ3 receptor activity. LAMP-1-expressing normal-sized platelets also displayed inverse associations with WB ɑ-thrombin-induced surface annexin V and mitochondrial damage, which are features of procoagulant platelets. Conclusions From the current descriptive work only involving type 2 diabetes, it is impossible to judge whether the findings are features of the disease or if they occur in healthy individuals as well. However, the study describes LAMP-1 expressing subpopulations of circulating normal-sized platelets that associate with WB α-thrombin (10 U/mL) responses in vitro. Increased proportions of such platelets induced lysosomal release and αIIbβ3 receptor activity, whereas lower proportions promoted WB agonist-induced procoagulant platelet creation. It is to hypothesize that the new described regulatory mechanism could in the future offer a possibility to influence platelet behavior in type 2 diabetes. Key messages Lysosomal exocytosis of circulating platelets influences reactivity, as determined by agonist-induced platelet reactions in vitro Thus, the low release of lysosomes by normal-sized platelets in vivo increases agonist-evoked procoagulant platelet production. Higher lysosomal exocytosis of circulating normal-sized platelets promotes platelet aggregation and secretion.

PLATELET SUPPRESSION BY TIROFIBAN AMELIORATES PULMONARY COAGULATION AND FIBRINOLYSIS ABNORMALITIES IN THE LUNGS OF MOUSE ANTIBODY-MEDIATED TRANSFUSION-RELATED ACUTE LUNG INJURY.

This study aimed to explore the ameliorating effects of the platelet surface glycoprotein IIb/IIIa receptor antagonist tirofiban on coagulation and fibrinolytic abnormalities in a mouse model of antibody-mediated transfusion-associated acute lung injury (ALI). This is important because ALI is a major cause of death attributable to the occurrence of adverse transfusion reactions. No information on a definite diagnosis or pathological mechanism exists, and targeted treatment options are not available. In this study, wild-type male Balb/c mice aged 8 to 10 weeks were randomly divided into the TRALI model, blank control, tirofiban intervention, and isotype control groups. After different treatment exposures, the mice were observed for 2 h before being killed, and lung tissue samples were collected. To explore the intervention effect of tirofiban, the degree of lung injury was quantified by estimating the lung wet/dry ratio, rectal temperature, survival rate, total protein, and myeloperoxidase and via hematoxylin-eosin staining. Furthermore, the coagulation, anticoagulation, and fibrinolysis assays were measured by automatic coagulation instrument and enzyme-linked immunosorbent assay kits, and the fluorescence densities of platelets and fibrin were quantified using immunofluorescence to analyze the effects of tirofiban on the platelet and fibrin interactions of TRALI. Compared with the TRALI model group, the lung injury indices in the tirofiban intervention group decreased significantly, and survival rates also improved. Furthermore, the level of coagulation and fibrinolytic abnormalities were obviously lower than those in the TRALI model group. In conclusion, our findings suggest that tirofiban might interfere with TRALI by inhibiting platelet activation and improving coagulation and fibrinolytic abnormalities.

Effect of Epitope Specific Antibodies on Single Platelet Physiology with Implications for Immune Thrombocytopenia Purpura

Background: Platelets play a vital role in both hemostasis and thrombosis and dysfunction thereof may lead to uncontrolled bleeding and clotting. Consequently, patients with Immune Thrombocytopenia Purpura (ITP) exhibit extremely low platelet counts caused by enhanced platelet clearance and destruction due to platelet reactive antibodies. However, even though all patients have thrombocytopenia, only 20 percent of ITP patients develop major bleeding episodes, which cannot be reliably predicted by platelet count alone. While platelet auto-antibodies have been investigated previously, whether epitope-specific antibodies directly affect platelet function remains poorly understood. To that end, we explored the possible physiological impacts of antibodies on single platelet adhesion, spreading, morphology and activation. Because 70% of platelet reactive antibodies in ITP are directed toward the integrin GPIIb/IIIa, we leveraged well-characterized monoclonal antibodies toward GPIIb/IIIa to better understand their physiological effects of platelet-fibrinogen interactions via the assays described above. Overall, we found that antibodies toward GPIIb/IIIa alter the functionality of individual platelets on fibrinogen surfaces in an epitope dependent manner. Most notably, antibodies that bound to either the head or tail region of αIIb (MBC 290.5 and MBC 314.5) increased the percent of platelets expressing phosphatidylserine, when compared to the control and antibodies binding to the head or tail region of βIIIa (AP3, AP5, and Libs 2). However, the mean intensity of this expression was on average much weaker than the βIIIa antibodies. This suggesting differing functional consequences of platelets to various epitopes and in turn could help explain the differing effects antibodies could have in ITP. Methods: Healthy donor platelets were diluted to 10 million/mL in Tyrode's modified HEPES buffer to ensure that single platelets were being measured and to reduce the number of platelet aggregates. These platelets were then incubated and adhered on 100 µg/mL human fibrinogen-coated coverslips for 2 hours in the presence of an antibody toward a selected epitope (Figure 1A). Adhered platelets were then stained with a cell membrane stain and Annexin V (PS exposure), fixed and then imaged with fluorescence microscopy. After imaging, thousands of platelets were then counted and analyzed. The antibody treated platelets were then normalized to the non-treated control. Results: Our preliminary data indicates an epitope-specific effect of antibodies on platelet physiology at the single cell level. Using well-characterized antibodies to various epitopes of GPIIb/IIIa (Figure 1A), we found that when compared to the non-antibody treated control, MBC 290.5 and Libs 2 decreased platelet spreading area by 29% and 31% respectively. However, while MBC 290.5 did not alter platelet density (n/mm²) Libs 2 enhanced platelet adhesion by increasing platelet density by 85%. This indicates the possible decrease in functionality of platelets treated with MBC 290.5. Additionally, both MBC 290.5 and MBC 314.5 increased the percentage of platelets that exposed PS by 97% and 87%, respectively, while AP3 and Libs 2 decreased the percentage of PS-exposed platelets by 64% and 49% respectively. Interestingly, although there was a decrease in the percent PS-exposed platelets, the mean intensity of the platelets that were PS exposed was much greater than the control with an increase of 360% and 228% respectively (Figure 1B). Conclusion: Although auto-antibodies cause platelet clearance, leading to low platelet counts, little is understood about the possible ramifications of antibodies on platelet behavior. Importantly, we show here that antibodies have a physiological consequence on platelets and different epitope-specific antibodies exhibit unique signatures for altering single platelet physiology, which could help explain how patients with ITP have varying clinical presentations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

In-vivo effects of Green laser radiation on hematological parameters of albino rats using direct exposure methods.

Laser beam has a thermal effect on the exposed body through oscillation of molecules. Rate of the vibrations depend on the time of exposure, intensity of the laser beam, the quantity of the absorbed dose, and the laser wavelength. Impacts of green laser beam on the hematological parameters of Albino Rats investigated in an in-vivo irradiation process. Green laser (200mW, 532nm) was used as a source of non-ionizing radiation to irradiate albino rats, the exposure carried out to heart position (in-vivo) of the rats directly. Fifteen female rats participated. Main blood components: white blood cells (WBC), red blood cells (RBC), and platelet (PLT) counts were evaluated using a direct exposure method for low and high radiation doses. High doses of laser beam affected the WBCs and PLTs significantly (P-value &lt; 0.05), and the low doses were not significant (P-value &gt; 0.05). Laser beam radiation affected on the main blood components at a limited time of exposure. Optimum radiation doses that had high effectiveness on blood component density depended on the type of blood components. As well as, high impacts (high significant) were on the density of PLT not RBCs. References FARHAD H M, JAAFAR M S, ISMAIL A H.( 2011). Control Light Delivery in PDT by Taking Account the Optical Properties of Hair Density on the Skin Surface. Journal of Modern Applied Science. 2 p.325-331. HUDA K.M., (2017). The effects of laser radiation on viscosity (PCV) of blood. Pak.J.Biotechnol . Vol.14, No.3 , pp.477-479. ISMAIL A. H., AND ABDULLA K. N., (2021). Biochemical and hematological study of the effects of annual exposure radiation doses on the operators of X-ray and CT-scan in some Erbil hospitals. Radiation Physics and Chemistry, Vol.184, 109466 KUTSCH, V. K. (1993). Laser in Dentistry. Jour. Amer. Dent. Asso. 124: 49-54. MARKOLF, H. N. (1996). Laser Tissue Interaction. Heidelberg, Germany. MUSTAFA S. AL MUSAWI, M. S. JAAFAR, B. AL-GAILANI, NASER M. AHMED, FATANAH M. SUHAIMI &amp; NURSAKINAH SUARDI ,Lasers in Medical Science volume 32, pages405–411(2017). MUSTAFA S.A., JAFAAR M.S., NASER M. A., AL-GAILANY B.T., FATANAH M. S., 2016. Effects of low power violet laser irradiation on red blood cells volume and erythrocyte sedimentation rate in human blood, Journal of physics; conference series, Vol.1875, 020005-1-020005-7. RAAD SH. ALNAYLI A., ZAHRAA S. S., FAID SH. H., HADEEL H. S. (2017).The Effect of LASER on Blood Viscosity and Its Influential Relation on the Rapidity of Red Blood Cells Precipitation . American International Journal of Research in Science, Technology, Engineering &amp; Mathematics, 19(1) pp.69- 74. SITI SAKINA M. F., SUARDI N., MUSTAFA I. S., (2018). In vitro UV-visible spectroscopy study of yellow laser irradiation on human blood. Journal of physics; conference series, Vol.995, 012053. THAIHAMMER.S, LAHR. A, CLEMENT, SENGEWALD. A, HESKL. W. M, BURGEMEISTER. R, AND SCHUTZE (2003) “Laser Micro tool in Cell Biology Medicine” laser physics ,13,5. VANENKO, M. &amp; HERING, P. (1998). Hard Tissue Ablation with Mechanically Q – Switched CO2 Laser. SPIE Proc. 3565:110 – 115. XU Q, MING Z, DART AM, DU XJVAN PELT LF. (2007). Optimizing dosage of ketamine and xylazine in murine echocardiography. Clin Exp Pharmacol Physiol. 4(5-6):499-507. ZAHRA AL- TIMIMI (2014). Investigating the Effects of Green Laser Irradiation on Red Blood Cells: Green Laser Blood Therapy. Int.Jou. of Applied Research and Studies.Vol.3, Issue 10,pp.1-5.

Main Factors Influencing the Platelet Spreading

To explore the main factors of platelet spreading and provide the foundation for related research. Platelets (2×107/ml) were draw from C57BL/6J mouse and kept at 22 ℃ for 1-2 hours. Platelets (2×107/ml) were were allowed to adhere and spread on the fibrinogen-coated slides, after staining F-actin in platelets, the platelets were observed with the confocal microscopy. The effects of different concentrations of fibrinogen (10 μg/ml, 30 μg/ml, 100 μg/ml) and kinds of agonists ［thrombin(0.01,0.05,0.1 U/ml), ADP（5,10,20 μmol/L）, U46619（0.125,0.25,0.5 μmol/L）］ on platelets were analyzed. The platelet spreading was successful if the spreading rate was higher after treated with agonists. Compared to the group which coated with 10 μg/ml and 100 μg/ml fibrinogen, the platelet density is optimal when coated with 30 μg/ml fibrinogen. In addition, under the stimulation of thrombin, ADP and U46619, the spreading rate of platelets showed a certain concentration-dependent increasing. The platelet spreading is easily influenced by various factors, the platelet spreading can be induced successfully at 0.1 U/ml thrombin, 20 μmol/L ADP and 0.5 μmol/L U46619 on the slide coated with 30 μg/ml fibrinogen.

A Novel Dynamical Analysis Method for Platelet Aggregation: From Traffic Flow to Blood Flow

This study proposed an ordinary differential equation model to simulate platelet aggregation by considering the Stokes viscosity resistance and interaction force between each platelet. This model is similar to the car-following traffic model, and its stability condition can be derived via long-wave expansion. The phase diagram can be divided into stable, metastable, and unstable regions. The theoretical results show that the flow viscosity and platelet diameter play essential roles in thrombus formation. The mKdV equation near the critical point is derived to describe the platelet density waves’ evolution properties by applying the reductive perturbation method. Furthermore, through the simulation of the space-time evolution of the distance distributions for platelets, it is shown that a smaller platelet diameter and lower viscosity will lead to thrombus formation, and the analytical results are consistent with the simulation results. The model indicates that thrombosis is similar to traffic congestion.

Structural transition of various-sized sphere-platelet mixtures.

Monte Carlo simulations on the structural change of hard sphere-platelet mixtures were performed to investigate the effect of particle size. We quantitatively analyzed local equilibrium structures of sphere-platelet mixtures with varying size ratios under various sphere and platelet density conditions. Based on the simulation results, we investigated the structural transitions such as isotropic to anisotropic, clustering, and so on. When a small amount of small-sized sphere is added to a large-sized platelet system, the mixture structure transitions from isotropic to nematic ones as the platelet number density increases. On the other hand, the platelet forms clusters with the addition of a large number of spheres. In a small platelet-large sphere system, the spheres form aggregates by increasing platelet density instead. The platelet and spherical particles exhibit different structural transitions depending on the size and density. In the limit of small and large size ratios, the structures of the platelet-sphere mixture obtained from the Monte Carlo simulation are close to those shown by previous theoretical and experimental studies, respectively. Because the primary actor shifts from sphere to platelet as the size ratio changes, the transition boundary shifts continuously. When the size ratio is close to unity, the most complicated behavior is observed, with both the platelet and sphere simultaneously acting the leading part.

Assembly of Graphene Platelets for Bioinspired, Stimuli-Responsive, Low Ice Adhesion Surfaces.

Design and fabrication of functional materials for anti-icing and deicing attract great attention from both the academic research and industry. Among them, the study of fish-scale-like materials has proved that enabling sequential rupture is an effective approach for weakening the intrinsic interface adhesion. Here, graphene platelets were utilized to construct fish-scale-like surfaces for easy ice detachment. Using a biomimicking arrangement of the graphene platelets, the surfaces were able to alter their structural morphology for the sequential rupture in response to external forces. With different packing densities of graphene platelets, all the surfaces showed universally at least 50% reduction in atomistic tensile ice adhesion strength. Because of the effect of sequential rupture, stronger ice–surface interactions did not lead to an obvious increase in ice adhesion. Interestingly, the high packing density of graphene platelets resulted in stable and reversible surface morphology in cyclic tensile and shearing tests, and subsequently high reproducibility of the sequential rupture mode. The fish-scale-like surfaces built and tested, together with the nanoscale deicing results, provided a close view of ice adhesion mechanics, which can promote future bioinspired, stress-responsive, anti-icing surface designs.

BIBLIOGRAPHIC REVIEW ON HOW IT AFFECTS THE MEAN PLATELET VOLUME IN CANCER

Introduction: Platelets are anucleated cytoplasmic fragments derived from megakaryocytes,they are oval in shape,1 to 2 millimeters in diameter, and have a half-life of 8 to 10 days. MPV is measured by automated cell counters based on impedance and optical effect, and can be modified by the anticoagulant ethylene aminotetraacetic acid (EDTA), temperature and storage time of the sample;Therefore,it is recommended that the analysis of the sample and its reading be carried out ideally in the first hour after taking the sample and preferably in the first 30 min. Another concept that is important to include in the interpretation of platelet activity is platelet mass,which is defined as the relationship between the platelet count and MPV; from which it has been found that the inverse platelet count-MPV relationship is not linear, so several normograms have been described to evaluate this relationship.3,4 The number, density and size of platelets is determined by a complex interaction between growth factors, cytokines, hormones and the megakaryocyte in the bone marrow. Megakaryopoiesis is programmed to maintain platelet function and mass, a mechanism in which thrombopoietin, granulocyte colony-stimulating factor, interleukins 1 and 6, and tumor necrosis factor are closely involved.Thrombopoietin levels are determined by gender and the number of platelets.In situations of stress,platelet production and mass are increased, resulting in the release into the circulation of large numbers of large, highly reactive platelets that migrate to sites of injury. An intense stimulus at the medullary level induces a hyperproduction of platelets that is characterized by a high MPV.

Ramifications of Vorticity on Aggregation and Activation of Platelets in Bi-Leaflet Mechanical Heart Valve: Fluid-Structure-Interaction Study.

Bileaflet mechanical heart valves (BMHV) are widely implanted to replace diseased heart valves. Despite many improvements in design, these valves still suffer from various complications, such as valve dysfunction, tissue overgrowth, hemolysis, and thromboembolism. Thrombosis and thromboembolism are believed to be initiated by platelet activation due to contact with foreign surfaces and nonphysiological flow patterns. The implantation of the valve causes nonphysiological patterns of vortex shedding behind the leaflets. This study signifies the importance of vorticity in platelet activation and aggregation in BMHV implants. A two-phase model with the first Eulerian phase for blood and the second discrete phase for platelets is used here. The generalized cross model of viscosity has been used to simulate the non-Newtonian viscosity of blood. A fluid-structure-interaction model has been used to simulate the motion of leaflets. This study has also estimated the platelet activation state (PAS), which is the mathematical estimation of the degree of activation of platelets due to flow-induced shear stresses that cause thrombus formation. The regions in the fluid domain with a higher vorticity field have been found to contain platelets with relatively higher PAS than regions with relatively lower vorticity fields. Also, this study has quantitatively reported the effect of vorticity on platelet aggregation. Platelet densities in fluid areas with higher vorticity are higher than densities in fluid areas with lower vorticity, indicating that highly activated platelets aggregate in areas with stronger vorticity.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use

Background and purposeGiven recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. Materials and methodsConsecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. ResultsA total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. ConclusionsOur study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

The retention of multivalent pollutants in mineral layers

Radioactive waste treatment is earning worldwide awareness due to the harmful impact of radiation emitted from these wastes to human health and environment. Clay can be used as effective adsorbent in order to remove radioactive pollutants in aqueous solution, and have great potential for ion exchange technique. In our study we investigated the montmorillonite clay using primitive model Grand canonical Monte Carlo (MC) simulations to describe the ion exchange or competition between the counterions of different valences. Throughout the study we introduced a formula representing the retention coefficient to quantify the ion exchange, which is essentially proportional to the more common distribution coefficientKd, and has the advantage of being dimensionless and more suitable for theoretical cases. we emphasized on the effect of surface charge density of clay platelets assumed to be negative, valence of the pollutants, and ground water reservoir concentrations of pollutants and of other cations. It is found that the retention is increased by increasing the valence of the pollutants, and the surface charge density, while it is decreased by increasing bulk concentration of pollutants and of other cations. Also it is found that the presence of high concentration of monovalent is less serious for the retention than the presence of multivalent ones.

Retaining the ‘art’: Painted Button-quail Turnix varius do make platelets in north-eastern Queensland

Button-quail Turnix spp. forage in a unique manner, leaving behind circular scratched depressions in the substrate known as platelets. These platelets offer an indirect method of surveying an otherwise cryptic and shy group of birds. Painted Button-quail T. varius are well known for creating platelets throughout most of their distribution. However, following 8 years of surveys from 1992 to 2000 in North Queensland, Nielsen (2000, p. 25) failed to locate any platelets and questioned whether Painted Button-quail in North Queensland may have “lost the art of forming platelets?”. During surveys in North Queensland between 2017 and 2022, we found extensive evidence at multiple locations of Painted Button-quail creating platelets that were consistent in size, shape, and placement with descriptions from elsewhere throughout the species’ distribution. A marked seasonal difference in occurrence and density of platelets was detected. Platelets were scarce from January to April, which coincides with the wet season, and increased in abundance throughout the dry season, with a peak at the end of the dry season (September–December). Platelets may represent a viable method for detecting Painted Button-quail in North Queensland, particularly during the dry season.

Understanding the Reinforcement of Graphene in Poly(Ether Ether Ketone)/Carbon Fibre Laminates.

PEEK appears as an excellent candidate to substitute epoxy resins in carbon fibre laminates for high-performance aeronautical applications. The optimization of the properties and, in particular, of the transition region between the fibres and the matrix appear as a major issue prior to serial production. Graphene, modified with two compatibilizers, has been incorporated in the polymer layer with the purpose of imparting additional functionalities and enhancing the matrix-fibre interaction. It is found that both carbon fibres and modified graphene significantly influence the crystallization behaviour and smaller, and/or more imperfect crystals appear while the degree of crystallinity decreases. Despite this, nanoindentation studies show that the PEEK layer exhibits significant modulus improvements (≈30%) for 5 wt.% of graphene. Most importantly, the study of the local mechanical properties by nanoindentation mapping allows the identification of remarkably high modulus values close to the carbon fibre front. Such a relevant mechanical enhancement can be associated with the accumulation of graphene platelets at the polymer–fibre boundary, as revealed by electron microscopy studies. The results offer a feasible route for interlaminar mechanical improvement based on the higher density of graphene platelets at the fibre front that should promote interfacial interactions. Concerning electrical conductivity, a large anisotropy was found for all laminates, and values in the range ~10−4 S/cm were found for the through-thickness arrangement as a consequence of the good consolidation of the laminates.