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Existing challenges with the early diagnosis of rheumatoid arthritis (RA) and active disease, mainly by non-rheumatologists, have prompted the search for novel biomarkers. Elevations in indices derived from blood cell counts, e.g., the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), have been reported in RA patients. However, their diagnostic accuracy has not been comprehensively assessed. Therefore, we conducted a systematic review and meta-analysis of studies reporting the sensitivity and specificity of the NLR and PLR, obtained by receiver operating characteristic (ROC) curve analysis, for the presence of RA and active disease. We searched electronic databases from inception to 15 March 2024 and assessed the risk of bias using the JBI Critical Appraisal Checklist (PROSPERO registration number: CRD42024533546). In 15 studies, the NLR exhibited acceptable accuracy for the presence of RA (area under the curve, AUC = 0.76, 95% CI 0.72 to 0.80) and active disease (AUC = 0.70, 95% CI 0.66 to 0.74). The PLR exhibited good accuracy for the presence of RA (AUC = 0.80, 95% CI 0.76 to 0.83). There were insufficient studies to assess the accuracy of the PLR for the presence of active disease. Our systematic review and meta-analysis suggests that the NLR and the PLR are promising biomarkers of RA (NLR and PLR) and active disease (NLR). Further research is required to investigate whether the NLR and PLR can significantly enhance the capacity to diagnose RA and active disease in clinical practice. [ABSTRACT FROM AUTHOR]

Depression is a common psychiatric disorder among patients undergoing maintenance haemodialysis (MHD). Depression may reportedly contribute to poor prognosis in several ways, including its effects on platelet function. We hypothesised that depression contributes to the occurrence of cardiocerebral vascular events (CCVE) and dysfunction of arteriovenous fistula (DAVF) in patients undergoing MHD through its effects on platelets. In this prospective cohort study, patients undergoing MHD were recruited and divided into depression and non-depression groups according to their Hamilton Depression Scale (HAMD) scores. The 286 enrolled patients had 103 occurrences of depressive symptoms (prevalence = 36.01%). Compared with the non-depression group, depression group had a significantly higher cumulative prevalence of CCVE and DAVF during follow-up. Cox regression analysis indicated that higher HAMD scores and lower plasma platelet distribution width (PDW) were common risk factors for CCVE and DAVF. Furthermore, HAMD scores were significantly negatively correlated with plasma PDW and was the main variable affecting changes in PDW, as indicated by multiple linear regression analysis. Depression may increase the risk of CCVE and DAVF in patients undergoing MHD by activating platelets. Plasma PDW may be a convenient indicator of platelet activation status and may predict the risk of CCVE and DAVF. [ABSTRACT FROM AUTHOR]

Background: Demographic and biochemical variations in newborn children as compared to adults are attributable to variable prognosis to blood transfusions. Aims of this mixed cohort study of Platelets with/without Plasma (PLT/PZ); only Plasma (PZ) transfusions in ≤ 24 months children is as follows: An Association of demography towards hospital mortality, and an association of laboratory investigations (LI) with hospital mortality. Methods: PLT/PZ (n = 72) and PZ (n = 79) children ≤ 24 months were followed up for a total length of hospital stay (LOS(D)). We calculated the Odds Ratio (OR) of demographic, and laboratory parameters for mortality, survival studies of demographic, laboratory parameters , Kaplan Meier Survival curve, Log-Rank significance (KMLR) and Multivariable regression (r2) with outcome as death. Results: The present study is in 2019–2022. Higher OR for hospital-based mortality for PLT/PZ and PZ cohort were age ≤ 1 m, weight ≤ 1500 g, preterm, gestational age ≤ 34 weeks, hospital length of stay {LOS(D)} 0–7 days, APGAR score ≤ 5, and Hb ≤ 7 g/dl. High OR, mortality was observed with Female gender, Length of stay before first transfusion {LOS(F)}, 0-7d, WHO Grade of bleeding (GOB) 4, PT>50 sec, INR>1·7, aPTT >75sec, PLT counts (μl) ≤25000/μl (PLT/PZ) and GOB 3, 4 (PZ). Higher OR for mortality was also observed with a lower derangement of coagulative parameters PT≤50s, INR ≤1·7, aPTT ≤75s (PZ). Higher survival was observed for (PLT/PZ) LOS(F) 0–7 days across age (m), weight (g) (P = 0·002; < 0·01), and INR ≤ 1·7; aPTT ≤ 75 s across LOS(D) (P < 0·01,0·018); (PZ) LOS(D) ≤ 7 days across age (m) and weight (g) (P = 0·036, 0·001); and GOB across LOS(D) (PLT/PZ; PZ) (P = 0·052, 0·005). Demography (PLT/PZ) r2 = 50·36% (P = 0·021), laboratory investigations r2 = 10·44% (P = 0·47), LOS(F) (P = 0·010), LOS(D) (P = 0·003), and GOB (P = 0·03) were the predictors. Demography (PZ) r2 (P = 0·095), investigations r2 = 8·79% (P = 0·254), LOS(D) (P = 0·026), and GOB (P = 0·012) were the predictors. Conclusions: PLT/PZ, demographic parameters, were significant cause of mortality with LOS(F), LOS(D), and GOB as predictors. PZ, demography attributed to mortality with LOS(D), and GOB as predictors. A higher OR of morality with lower derangement of laboratory profile is indicative of unnecessary transfusions in the age group. Laboratory investigations by themselves are not significant predictors of mortality. [ABSTRACT FROM AUTHOR]

Several investigations are being done to increase the short lifetime of mesenchymal stem cells (MSCs). One of the crucial genes involved in the immortalization of MSCs, hTERT (human telomerase reverse transcriptase), is activated in most publications using viral-based techniques. In this work, we investigated the use of platelet-derived (PMPs) and B cell precursor leukemia-derived microparticles as a nonviral method to trigger and compare the expression of the hTERT gene in MSCs. MSCs were extracted from the umbilical cord for the current investigation and identified using a flow cytometry approach and an inverted microscope. The Nalm-6 cell line and platelet concentrate were used to isolate microparticles (MPs). MSCs and MPs were cocultured for 14 days at 25-, 50-, and 100 μg/ml concentrations. qRT-PCR was used to research the expression of the hTERT gene. SPSS 26.0's t test was used to compare the outcomes. After coculture with platelet MPs, MSCs had higher levels of hTERT gene expression than the control group. In contrast, this gene's expression was concurrently decreased in MSCs exposed to MPs generated from Nalm-6. We demonstrated that following 14-day treatment, PMP significantly boosted the hTERT gene expression in MSCs, while the Nalm-6 MPs lowered the gene expression. However, additional studies are necessary due to the stability of hTERT gene expression and the immortalization of MSCs following exposure. [ABSTRACT FROM AUTHOR]

The platelet/high-density lipoprotein ratio (PHR) has been identified as a significant indicator of inflammation and a hypercoagulable state, demonstrating a strong link with the severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, its correlation with hyperuricemia has not yet been documented. This study utilized a cross-sectional design, analyzing data collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 in the United States. The platelet/high-density lipoprotein ratio (PHR) was determined by dividing the number of platelets (PLT) by the level of high-density lipoprotein cholesterol (HDL-C). We employed multivariable logistic regression analyses, generalized additive models, and subgroup analyses to investigate the correlation between PHR and hyperuricemia. The study revealed a hyperuricemia prevalence of 18.56%. Analysis indicated a significant positive correlation between PHR and the risk of hyperuricemia (OR 1.11, 95% CI 1.08, 1.14). This correlation remained consistent across different subgroups including age, ethnicity, gender, and body mass index (BMI). Smooth curve fitting demonstrated a saturation effect between PHR and the risk of hyperuricemia. PHR is positively correlated with hyperuricemia and may serve as a novel biomarker for predicting the onset of this condition. Additionally, targeted interventions to improve PHR might help reduce the incidence of hyperuricemia. [ABSTRACT FROM AUTHOR]

Introduction: To determine a cut-off value for systemic immune-inflammation index (SII) (neutrophil × platelet/lymphocyte) in the prediction of fetal growth restriction (FGR). Materials and methods: This case–control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. Singleton pregnant women with late-onset FGR who were followed up in outpatient clinics or hospitalized and whose pregnancy resulted at our hospital were included in the study group (group I). Healthy early and full-term singleton pregnant women with spontaneous labor who were followed up in the same hospital and whose pregnancy resulted at the same hospital were included in the control group (group II). Receiver-operating characteristic curves were used to assess the performance of SII value in predicting FGR. Results: We recruited 79 cases (pregnant with late-onset fetal growth restriction) and 79 controls (healthy pregnant), matched for age, body mass index, and parity. ΔSII was statistically significantly higher in the pregnant with late-onset FGR compared with healthy pregnant (123 vs − 65; p = 0.039). The values in ROC curves with the best balance of sensitivity/specificity were > 152 109/L (49% sensitivity, 70% specificity) and > 586 109/L (27% sensitivity, 90% specificity) for late-onset FGR. Discussion: Higher ΔSII levels in maternal blood indicate an inflammatory process causing FGR. The cut-off value for ΔSII (> 586 109/L) at 90% specificity can be used as a screening test. In the presence of ΔSII levels > 586 109/L (27% sensitivity and 90% specificity), the physicians should be more cautious about risk for FGR. Therefore, pregnant women at risk for FGR should be checked more frequently and monitored closely. However, further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). Methods: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. Results: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = − 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). Conclusion: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states. [ABSTRACT FROM AUTHOR]

Friction has been considered to mediate physiological activities of cells, however, the biological friction between a single cell and its ligand-bound surface has not been thoroughly explored. Herein, we established a friction model for single cells based on an atomic force microscopy (AFM) combined with an inverted fluorescence microscopy (IFM) to study the friction between a highly sensitive platelet and fibrinogen-coated surface. The study revealed that the friction between the platelet and fibrinogen-coated tip is mainly influenced by specific ligand–receptor interaction. Further, we modeled the biological friction, which consists of specific interaction, non-specific interaction, and mechanical effect. Besides, the results suggested that the velocity can also affect specific ligand–receptor interactions, resulting in the friction change and platelet adhesion to fibrinogen surfaces. The study built a friction model between a single cell and its ligand-bound surface and provided a potential method to study the biological friction by the combination of AFM and IFM. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic marker in several types of malignant tumors. Prognostic value of HALP score remains unclear for MDS. To determine the prognostic value of baseline HALP score in MDS. We retrospectively analyzed data from 130 newly diagnosed MDS patients evaluated and classified under HALP score. By the receiver operating characteristic (ROC) analysis, the optimal cut-off value of HALP was > 67.5 in predicting mortality. Patients were divided into two groups: with low and high HALP scores, and the characteristics were compared between both groups. Patients' median age was 68 (19–84) years, and 79 (60.8%) were male. Higher HALP score was detected in MDS patients with intermediate-risk under IPSS score, and at high and very high risks under IPSS-R score, and those receiving azacitidine (AZA) treatment. The survival rates of those with a HALP score > 67.5 were significantly lower than those with low HALP score at 17.77 ± 3.98 (median ± SE) (p < 0.001). The 3-, 5- and 10-years survival rates of individuals with HALP scores > 67.5 were found as 25, 18, and 11%, respectively. Median overall survival (OS) was also determined as 33.10 (95% CI 16.34–49.88) months by the Kaplan–Meier method. HALP score has shown an ability to be a useful prognostic biomarker in various cancers, including MDS. The meaningful cut-off value of HALP is disease-specific and largely study-specific. High HALP score is associated with unfavorable clinicopathological characteristics. Also, it may be useful in predicting OS and mortality of MDS. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is a critical form of Acute Lung Injury (ALI), challenging clinical diagnosis and severity assessment. This study evaluates the potential utility of various hematological markers in burn-mediated ARDS, including Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), MPV-to-Lymphocyte Ratio (MPVLR), Platelet count, and Platelet Distribution Width (PDW). Employing a retrospective analysis of data collected over 12 years, this study focuses on the relationship between these hematological markers and ARDS diagnosis and severity in hospitalized patients. The study establishes NLR as a reliable systemic inflammation marker associated with ARDS severity. Elevated MPV and MPVLR also emerged as significant markers correlating with adverse outcomes. These findings suggest these economical, routinely measured markers can enhance traditional clinical criteria, offering a more objective approach to ARDS diagnosis and severity assessment. Hematological markers such as NLR, MPV, MPVLR, Platelet count, and PDW could be invaluable in clinical settings for diagnosing and assessing ARDS severity. They offer a cost-effective, accessible means to improve diagnostic accuracy and patient stratification in ARDS. However, further prospective studies are necessary to confirm these findings and investigate their integration with other diagnostic tools in diverse clinical settings. [ABSTRACT FROM AUTHOR]

Objective: To determine the predictors for chronic and/or persistent immune thrombocytopenia (ITP) among children with newly diagnosed ITP. Methods: Ours was a mixed-design study (prospective: January 2020 to March 2022 and retrospective: January 2014 to December 2019), wherein we enrolled children, aged 1 month to 18 years presenting with newly diagnosed ITP. Results: Of the 64 enrolled participants, 58 were followed up for atleast 1-year duration and 6 children were followed up for 3 to 12 months' duration. The median (IQR) age of the cohort was 8 (5, 11) years with a female preponderance (62.5%). Wet bleeding was seen in 56%; 6.25% developed intracranial bleeding. 67.2% (43/64) and 41.4% (24/58) children developed persistent and chronic ITP, respectively. Of the 34 children who achieved complete response at 12-months follow up, 21 (62%) achieved complete response by 3 months and the rest achieved complete response over the next 9 months. Development of overall response (complete or partial) at 3 and 12 months, was associated with a higher absolute lymphocyte count (ALC) at admission. The median ALC (×103/µL) at admission was 3.77 and 2.87 in children who had overall response and no response at 3 months, respectively (P = 0.03). The median ALC (×103/µL) at admission was 3.99 and 2.96 in children who had overall response and no response at 12 months, respectively (P = 0.04). Response rate was lesser in the treated group by approximately 10% compared to the non-treated group. Conclusion: The rate of chronicity and intracranial bleeding in our cohort is more than the reported rates in literature. Higher ALC was found to be associated with response. [ABSTRACT FROM AUTHOR]

Background: The current understanding emphasizes the intricate interplay between the Leukemic cell and its environment. Platelet-derived microparticles play a crucial role in facilitating intercellular communication and contribute to the complex landscape of cancer pathology. This study aimed to investigate the influence of platelet-derived microparticles on cell proliferation, apoptosis, and the expression of key genes, including P53, P21, Cyclin D1, Bax, and Bcl-2, within the context of a chronic myeloid leukemia cell line (K562). Methods and results: Platelet-derived microparticles were obtained through centrifugation at various speeds, and their concentration was quantified using the BCA assay. To determine the size and immunophenotypic characteristics of the PMPs, both the DLS technique and flow cytometry were employed. Cell proliferation was assessed using the MTT assay and hemocytometer, and cell cycle analysis was conducted through DNA content evaluation. Real-time PCR was utilized for gene expression analysis of Bax, Bcl-2, Cyclin D1, P53, and P21. Flow cytometry was employed to examine cell apoptosis. The findings revealed that platelet-derived microparticles have the ability to decrease proliferation of the K562 cell line, while not exerting an impact on apoptosis and cell cycle progression. Analysis through real-time PCR indicated an upregulation in the gene expression of P53, P21, and Bcl-2, accompanied by a downregulation in Bax and Cyclin D1. Conclusion: This investigation sheds light on the intricate relationship between chronic myeloid leukemia and its microenvironment, particularly the involvement of platelet-derived microparticles. The study underscores the potential of platelet-derived microparticles to influence cell behavior and gene expression, providing a deeper understanding of their role in CML and its therapeutic implications. [ABSTRACT FROM AUTHOR]

Vaterite microparticles, metastable form of calcium carbonate, are promising forms of delivery of medicinal compounds. For more efficient delivery of target molecules (increased incorporation and retention), vaterite microparticles must be functionalized with biopolymers. In this article the effect of polysaccharides, mucin and vaterite microparticles, as well as hybrid vaterite microparticles with the above-mentioned biopolymers was studied on platelet aggregation. It was found that fucoidan, heparin and dextran sulfate (when added to platelet-rich plasma) and mucin (when added to isolated platelets) initiated cell aggregation. Pectin and chondroitin sulfate inhibited ADP- and thrombin-induced aggregation in a dose-dependent manner, mucin suppressed ADP-induced, and dextran sulfate suppressed thrombin-induced platelet aggregation. Vaterite microparticles at a concentration of 100–1000 µg/mL did not affect the aggregation of isolated platelets, but caused 10–15% cell aggregation in plasma; at the same time, at a concentration of 1000 µg/mL vaterite microparticles prevented agonist-induced cell aggregation by ~30%. It has been established that hybrid vaterite microparticles with fucoidan or heparin, when added both to platelet-rich plasma and to isolated cells, are capable to initiate platelet aggregation. Vaterite microparticles functionalized with pectin or chondroitin sulfate had no effect on spontaneous cell aggregation, and did not affect (with chondroitin sulfate) or inhibit (with pectin) agonist-induced platelet aggregation. Thus, the use of hybrid vaterite microparticles with pectin or fucoidan/heparin may be promising for the delivery of drugs aimed at modulating (inhibition with pectin or activation with fucoidan/heparin) the platelet component of hemostasis. [ABSTRACT FROM AUTHOR]

The symptoms in patients with primary immune thrombocytopenia (ITP) after COVID-19 onset remain largely unclear. The aim of this study was to describe the platelet count fluctuations in ITP patients following the diagnosis of COVID-19. A prospective multicentre observational study was conducted from December 15th, 2022, to January 31st, 2023 in 39 general hospitals across China. Patients with preexisting primary ITP who were newly diagnosed with COVID-19 were enrolled. A total of 1216 ITP patients with newly-diagnosed COVID-19 were enrolled. 375 (30.8%) patients experienced ITP exacerbation within eight weeks after the diagnosis of COVID-19, and most exacerbation (266/375, 70.9%) developed in the first two weeks. Immunosuppressive therapy for ITP and severe/critical COVID-19 infection were independent variables associated with ITP exacerbation. Overall the platelet count had a transient increasing trend, and the platelet peak value occurred at two weeks after COVID-19 infection. Then, the platelet count decreased to the baseline level in the following weeks. The platelet count had a transient increasing trend in ITP patients following the diagnosis of COVID-19. ITP exacerbation only occurred in less than one-third of ITP patients. Nonimmunosuppressive therapy may have an advantage to prevent ITP exacerbation during COVID-19. [ABSTRACT FROM AUTHOR]

Platelets are one of the coagulation cells. When platelet activation occurs, many mediators are released and affect endothelial cells (ECs) and lead to endothelial dysfunction (ED). ED plays an important role in the pathogenesis of many diseases, including cardiovascular disease (CVD). Platelet are of important factors in ED. The release of mediators by platelets causes the stimulation of inflammatory pathways, oxidative stress, and apoptosis, which ultimately result in ED. On the other hand, platelet activation in CVD patients can be associated with a bad prognosis. Platelet activation can increase the level of markers such as p-selectin in the serum. Also, in this study, we have discussed the role of platelet as a diagnostic factor, as well as its use as a treatment option. In addition, we discussed some of the molecular pathways that are used to target platelet activation. [ABSTRACT FROM AUTHOR]

The present investigations theoretically explored MXene-based dissimilar-shaped nanoparticle (CuO spherical, MWCNT cylindrical, Al2O3 blade, graphene platelet, and Fe3O4 brick shapes) hybrid nanofluids by 1% v/v, in a triple-tube heat exchanger (TTHX). The shape and surface effect thermophysical properties of nanofluids have been specified using a user-defined function. The operating fluid mass flow rate and temperature of inner (water), intermediate (hybrid nanofluids), and outer tubes(water) are 0.1kg s−1 at 30 ºC, 0.1–0.5kg s−1 at 70◦C, and 0.1kg −1s at 20 ºC, respectively. The comparative thermal performance (effectiveness, heat transfer, thermal enhancement factor, London factor, etc.), exergetic analysis (entropy production, exergy destruction, etc.), and cost–benefit ratio (CBR) have been explored. MXene-spherical hybrid nanofluid is 5.16% more efficient than water at 0.1kg s−1 in the TTHX system. MXene-cylindrical hybrid nanofluid exhibits 11.23% and 12.69% better heat transfer and performance index than DI water at the lowest mass flow rate in the TTHX system. MXene-platelet hybrid nanofluids show a reduced Nusselt number ratio for the tested mass flow rates. Entropy generation in MXene-cylindrical hybrid nanofluid is 24.11% lower than in DI water.The highest thermal performance factor (TPF) of MXene-cylindrical hybrid nanofluid in the TTHX is 1.65. The MXene-cylindrical hybrid nanofluid is the most economical in the TTHX system, followed by the MXene-brick hybrid nanofluid. Overall, Mxene-cylindrical hybrid nanofluids perform best in the TTHX system in terms of heat transfer rate, TPF, and CBR in the TTHX system. [ABSTRACT FROM AUTHOR]

Blood flow disorders are often the result of the non-physiological narrowing of blood arteries caused by atherosclerosis and thrombus. The blood then proceeds through rising-peak-decreasing phases as it passes through the narrow area. Although abnormally high shear is known to activate platelets, the shear process that platelets undergo in small arteries is complex. Thus, understanding how each shear phase affects platelet activation can be used to improve antiplatelet therapy and decrease the risk of side effects like bleeding. Blood samples were sheared (68.8 ms,5200 s−1) in vitro by the microfluidic technique, and platelet activation levels (P-selectin and integrin αIIbβ3) and von Willebrand factor (vWF) binding to platelets were analyzed by flow cytometry. Post-stenosis platelet aggregation was dynamically detected using microfluidic technology. We studied TXA2, P2Y12-ADP, and integrin αIIbβ3-fibrinogen receptor pathways by adding antiplatelet drugs, such as acetylsalicylic acid (ASA, an active ingredient of aspirin that inhibits platelet metabolism), ticagrelor (hinders platelet activation), and tirofiban (blocks integrin αIIbβ3 receptor) in vitro, respectively, to determine platelet activation function mediated by transient non-physiological high shear rates. We demonstrated that platelets can be activated under transient pathological high shear rates. The shear rise and fall phases influenced shear-induced platelet activation by regulating the binding of vWF to platelets. The degree of platelet activation and aggregation increased with multiple shear rise and fall phases. ASA did not inhibit shear-mediated platelet activation, but ticagrelor and tirofiban effectively inhibited shear-mediated platelet activation. Our data demonstrated that the shear rise and fall phases play an important role in shear-mediated platelet activation and promote platelet activation and aggregation in a vWF-dependent manner. Blocking integrin αIIbβ3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation. [ABSTRACT FROM AUTHOR]

Exosomes have come to the fore in drug delivery systems due to their biological-based and immune-suppressing properties. In this study, we investigated the effect of doxorubicin loading of exosomes isolated from human platelets on breast cancer. Exosomes released from ADP (1 µM)-activated platelets were isolated by the ultracentrifugation method, and their size and charge were measured with a TEM and zeta sizer. Then doxorubicin (Dox) loading into exosomes (PLT-Exo-Dox) was done by electroporation and incubated with MDA-MB-231 cells. In exosome characterization, CD62 positivity was higher in platelet pellets, while CD9 positivity was higher in released exosomes. The size of PLT-Exo and PLT-Exo-Dox was 82.02 ± 5.21 nm and 116 ± 3.73 nm, with a polydispersity index of 0.26 ± 0.04 and 0.39 ± 0.06, and the Zeta potential was − 16.45 mV and 24.07 mV, respectively. The encapsulation efficiency of the preparation was 86.02 ± 6.16%, with a drug loading capacity of 4.75 ± 0.16 µg/µg of the exosome. In MDA-MB-231 cells, PLT-Exo increased cell viability, while PLT-Exo-Dox decreased in 24 h. The Annexin-V binding level and Bax gene expression were increased in PLT-Exo-Dox and Bcl-2 gene expression was decreased. This study will shed light on the development of release systems that can be effective with chemotherapeutic agents by using exosomes released by cells in the development of personalized treatments. [ABSTRACT FROM AUTHOR]

This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis (DVT) mouse. In the control and sham mice, the walls of deep vein were regular and smooth with intact intima, myometrium and adventitia. The blood vessel was wrapped with the tissue and there was no thrombosis in the lumen. In the DVT model, the wall was uneven with thicken intima, myometrium and adventitia. After treated with fucoidans LF1 and LF2, the thrombus was dissolved and the blood vessel was recanalized. Compared with the control group, the ROS content, ET-1 and VWF content and the expression of PKC-β and NF-κB in the model were significantly higher (P < 0.05); these levels were significantly reduced following treatments with LF2 and LF1. Compared with H2O2 treated-HUVECs, combined LF1 and LF2 treatment resulted in significant decrease in the expression of PKC-β, NF-κB, VWF and TM protein (P < 0.05). It is clear that LF1 and LF2 reduces DVT-induced ET-1, VWF and TM expressions and production of ROS, thus inhibiting the activation of PKC-β/NF-κB signal pathway and the activation of coagulation system and ultimately reducing the formation of venous thrombus. [ABSTRACT FROM AUTHOR]

This review will discuss evidence that aspirin possesses anticancer activity. Long-term observational retrospective studies on nurses and health professionals demonstrated that regular aspirin users had a significantly lower incidence of colorectal cancer (RCT). Prospective studies on patients with a high risk of developing colorectal polyps/cancer confirmed that aspirin use significantly lowered colorectal dysplasia. Numerous observational studies focused on the use of aspirin in a broad range of cancers demonstrating a consistent 20–30% preventive effect on cancer incidence and mortality. Random Controlled Trials provided conflicting results on the benefit of aspirin in preventing CRC. Based on the age, weight/body size of the subjects for reasons still being explored. Studies on rats/mice further demonstrated that treatment of animals with aspirin where colon cancer was induced chemically or genetically (APCMin mice) reduced colonic dysplasia and polyp formation. Aspirin treatment was also effective at reducing the growth of cancer cells transplanted into normal/immunocompromised mice, suggesting that aspirin may be effective in treating different cancers. This possibility is also supported in clinical studies that aspirin use pre- and postcancer diagnosis significantly reduced the metastatic spread of cancer and increased patient survival. Lastly, the importance of the antiplatelet actions of aspirin in the drug's anticancer activity and specifically cancer metastatic spread is discussed and the current controversy related to the conflicting recommendations of the USPSTF over the past five years on the use of aspirin to prevent CRC. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) has significant potential for various applications and holds clinical value in regenerative medicine. Cryopreservation is used to extend the preservation period of PRP, facilitating its clinical application. However, the potential negative effects of long-term cryopreservation on platelet storage lesion are still uncertain. In this study, PRP was stored at − 30 °C or − 80 °C. Platelet count, apoptosis, reactive oxygen species (ROS) content, and CD62P expression were assessed on the 14th and 28th days. The study also evaluated platelet mitochondria morphology and function, serotonin (5-HT) secretion by platelets, and the inflammatory activating effect of cryopreserved platelets in PRP. The results showed that there were no significant differences in platelet count, the content of 5-HT, and inflammatory effects between fresh PRP and PRP cryopreserved at both − 30 °C and − 80 °C. However, there was an increase in ROS level, apoptosis, and CD62P level after cryopreservation at both temperatures. Additionally, the levels of ROS, apoptosis, and CD62P in platelets were similar after storage at − 30 °C and − 80 °C. The main difference observed was that the morphology and function of mitochondria were severely damaged after storage at − 30 °C, while they were less affected at − 80 °C. Based on these findings, it can be concluded that storing PRP at − 80 °C is more suitable for achieving a better therapeutic effect in clinical applications, but cryopreservation could not replace the current standard. [ABSTRACT FROM AUTHOR]

Purpose: Patients with liver cirrhosis sometimes suffer from high recurrence rates and postoperative complications. We previously reported that platelet-related hematological parameters are associated with the outcomes after incisional herniorrhaphy, and aim to evaluate the predictive value of these criteria in cirrhotic patients undergoing open umbilical herniorrhaphy. Methods: This is a retrospective study. The data of 95 cirrhotic patients undergoing open umbilical herniorrhaphy were analyzed. Patients were grouped based on the recurrence and defined hematological values. Platelet–multiple-lymphocyte index (PLM), neutrophil–leukocyte ratio, lymphocyte–monocyte ratio, platelet–neutrophil ratio, systemic immune-inflammation index, and aspartate aminotransferase–leukocyte ratio values were calculated based on preoperative blood analyses. The outcomes were obtained from hospital records and follow-up calls to patients. Results: Using cutoff values acquired by the Youden Index, we found a PLM value < 27.9, and the history of inguinal herniorrhaphy were revealed to be statistically significant in the recurrence based on univariant and multivariant analyses (p < 0.05). We further divided patients into two groups based on the cutoff value of PLM and found that a PLM value < 27.9 was significantly associated with the recurrence of incisional hernias (p = 0.018) and the occurrence of postoperative foreign sensation (p = 0.044), and tended to result in other postoperative complications such as cardiopathy, respiratory infection, hypoproteinemia, and hepatic diseases (p = 0.089). Conclusion: The preoperative hematological values, especially PLM, may indicate the outcomes in cirrhotic patients after open umbilical herniorrhaphy. Accurate identification of risks may alert the intraoperative and postoperative care for patients. [ABSTRACT FROM AUTHOR]

The blood coagulation system is actively involved in the development of cancer. Many solid tumors express tissue factor (TF) that triggers a plasma coagulation cascade leading to an increased risk of cancer-associated thrombosis and venous thrombosis in cancer patients. The main components of the blood clots, platelets are also well known for their role in cancer metastasis as they bind to tumor cells once they enter blood vessels and "shield" them to escape immune surveillance. Platelets also promote adhesion and extravasation of circulating tumor cells into tissues and subsequent metastasis formation. Moreover, being mobile carriers of various growth factors, platelets are actively recruited and, in some cases, engulfed by the tumor, contributing thereby to tumor development and vascularization. Platelet recruitment occurs through both tumor-induced thrombin activation and exposing of platelet-adhesive surfaces by the tumor. Activated in the tumor proximity, platelets attract and induce neutrophil activation and the formation of neutrophil extracellular traps (NETs), thus modulating the tumor microenvironment. Apart from direct interaction, platelets and tumor cells exchange mRNA, miRNA and other regulatory molecules via microvesicles, with platelets serving as "containers" that spread tumor genetic material (circulating nucleic acids) throughout the organism. In this review, we address the molecular mechanisms behind the platelet involvement in the growth and metastasis of solid tumors, and discuss possible options for the pharmacological interruption of platelet–tumor cell interaction. [ABSTRACT FROM AUTHOR]

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2. [ABSTRACT FROM AUTHOR]

Cobalt–chromium alloys are often employed in those environments that require reliable wear and friction properties. Cold Gas Dynamic Spray offers the opportunity to obtain good quality deposits of Stellite-6, that can be successfully used in harsh environments, where good surface performance, in terms of wear resistance, is required. It is also well-known that Stellite-6 is subjected to several physical changes at the interface during dry sliding, that are often related to the loading conditions. As a consequence, wear behavior of this alloy can undergo some variations that linear models are not able to capture, since micro-structural modifications occur during operation. To better understand the wear mechanisms of cold-sprayed Stellite-6 coatings together with the occurring physical phenomena, a systematic experimental study was performed, in fact, to date, no such in-depth tribological studies have been performed. Tests were conducted under combinations of two sliding speeds (0.1 and 0.5 m/s) and four contact pressure in the range of 2-5 MPa. In low-speed tests, abrasive wear is evident, where detachment and pull-out phenomena mainly affect the worn surface of coatings. On the other hand, subsurface cracking was observed in high-speed tests, as well as evidence of plastic deformation on the wear surface. These results suggest that observed wear mechanisms are more likely a consequence of adhesive wear. Unique to this study, the cross-sectional nano-indentation tests showed how the stiffness of the coating, near to wear interface, increases significantly in the case of the lowest value of sliding speed (i.e., v = 0.1 m/s), whereas tends to decrease at high speeds, i.e., v = 0.5 m/s, as a consequence of the formation of subsurface cracks into the coating. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of C-reactive protein (CRP) on the prognosis of adult patients with Immune thrombocytopenia purpura (ITP). A retrospective study of 628 adult ITP patients, as well as 100 healthy and 100 infected patients, attending the Affiliated Hospital of Xuzhou Medical University from January 2017 to June 2022 was performed. The ITP patients were grouped according to their CRP levels, and the differences in clinical characteristics of each group and the influencing factors of efficacy in newly diagnosed ITP patients were analyzed. CRP levels were significantly higher in the ITP and infected groups compared with healthy controls (P < 0.001), and platelet counts were significantly lower in the ITP group (P < 0.001). Between the CRP normal and elevated group, their age, white blood cell count, neutrophil count, lymphocyte count, red blood cell count, hemoglobin, platelet count, complement C3 and C4, PAIgG, bleeding score, proportion of severe ITP, and proportion of refractory ITP were significantly different (P < 0.05). Patients of severe ITP (P < 0.001), refractory ITP (P = 0.002), and with active bleeding (P < 0.001) had significantly higher CRP levels. Patients with no response after treatment had significantly higher CRP levels than those who achieved CR or R (P < 0.001). Platelet counts (r = − 0.261, P < 0.001) in newly diagnosed ITP patients and treatment outcomes (r = − 0.221, P < 0.001) were negatively correlated with CRP levels, and bleeding score was positively correlated with CRP levels (r = 0.207, P < 0.001). Treatment outcome was positively correlated with decrease in CRP levels (r = 0.313, P = 0.027). A multifactorial regression analysis of the influencing factors of treatment outcomes on newly diagnosed patients found that CRP was an independent risk factor of the prognosis (P = 0.011). In conclusion, CRP can help assess the severity and predict the prognosis of ITP patients. [ABSTRACT FROM AUTHOR]

Thrombosis has been associated with severity and mortality in COVID-19. SARS-CoV-2 infects the host via its spike protein. However, direct effects of spike proteins from SARS-CoV-2 variants on platelet activity and coagulability have not been examined. An ethically approved ex vivo study was performed under a preplanned power analysis. Venous blood was collected from 6 healthy subjects who gave prior written consent. The samples were divided into 5 groups: without spike proteins (group N) and with spike proteins derived from alpha, beta, gamma, and delta SARS-CoV-2 variants (groups A, B, C, and D, respectively). Platelet aggregability, P-selectin expression, platelet-associated complement-1 (PAC-1) binding, platelet count, and mean platelet volume (MPV) were measured in all 5 groups, and thromboelastography (TEG) parameters were measured in groups N and D. The % change in each parameter in groups A to D was calculated relative to the value in group N. Data were analyzed by Friedman test, except for TEG parameters, which were evaluated by Wilcoxon matched pairs test. P < 0.05 was considered significant. This study included 6 participants based on a power analysis. There were no significant differences in platelet aggregability under stimulation with adenosine diphosphate 5 µg/ml, collagen 0.2 or 0.5 µg/ml, and Ser-Phe-Leu-Leu-Arg-Asn-amide trifluoroacetate salt (SFLLRN) 0.5 or 1 µM in groups A–D compared to group N. There were also no significant differences in P-selectin expression and PAC-1 binding under basal conditions or SFLLRN stimulation, and no significant differences in platelet count, MPV and TEG parameters. Platelet hyperactivity and blood hypercoagulability have been reported in COVID-19 patients, but spike proteins at 5 µg/ml from SARS-CoV-2 variants (alpha, beta, gamma, delta) did not directly cause these effects in an ex vivo study. This study was approved by the Ethics Committee of Kyoto University Hospital (R0978-1) on March 06, 2020. [ABSTRACT FROM AUTHOR]

Summary: Background: In this retrospective study the effects of the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), mean platelet volume to platelet count ratio (MPV/PC) values as well as C‑reactive protein (CRP) and procalcitonin (PCT) levels on the severity and mortality in critically ill child trauma cases were evaluated. Methods: A total of 80 trauma cases aged 31 days to 16 years that were followed-up in the pediatric intensive care unit (PICU) were included in the study. The data of the patients on the first day of hospitalization (T1), the median day of intensive care admission (T2), and before discharge or exitus (T3) were analyzed. The cases were divided into three groups according to the injury severity score (ISS) as minor, moderate, and severe. Results: Of the 80 cases 59 (73.75%) were male and 21 (26.25%) were female. The mean age of all the cases was 54.5 ± 47.8 months, and the mean PICU stay was 7.35 ± 6.64 days. Of the cases 19 (23.75%) due to motor vehicle accidents and 61 (76.25%) due to falling from heights were followed-up. The mortality rate was found to be 13.75% (11 cases). The T1, T2 and T3 NLR, MLR, MPV/PC and PCT values did not differ between the groups. The T1 and T2 CRP levels were higher in the moderate trauma group than in the severe trauma group. Also, ISS and pediatric risk of mortality 3 (PRISM-3) scores were higher while the revised injury severity classification version II (RISC II), RISC II survival and Glasgow coma scale (GCS) scores were lower in the nonsurvivors. While the T3 MLR value was lower in nonsurvival cases, the T3 MPV/PC value was found to be higher. Conclusion: The NLR, MLR, and MPV/PC values do not predict the severity of the trauma in children. In children with severe trauma, low MLR and high MPV/PC values can be used to predict mortality. [ABSTRACT FROM AUTHOR]

Understanding the pharmacodynamic effects of platelet inhibitors is standard for developing more effective antithrombotic therapies. An example is the antithrombotic treatment of acute coronary syndrome (ACS), in particular ST-elevated myocardial infarction (STEMI) patients who are in need for rapid acting strong antithrombotic therapy despite the use of aspirin and oral P2Y12-inhibitors. In this study, we evaluated two injectable platelet inhibitors under clinical development (the P2Y12 antagonist selatogrel and the GPIIb-IIIa antagonist zalunfiban) that may be amenable to pre-hospital treatment of STEMI patients. Platelet reactivity was assessed at inhibitor concentrations that represent clinically relevant levels of platelet inhibition (IC20-50%, 1/2Cmax, and Cmax). Light transmission aggregometry (LTA), was used to evaluate the initial rate of aggregation (primary slope, PS) and maximal aggregation (MA). Both adenosine diphosphate (ADP) and thrombin receptor agonist peptide (TRAP) were used as agonists. Zalunfiban demonstrated similar inhibition of platelet aggregation when blood was collected in PPACK or TSC, whereas selatogrel demonstrated greater inhibition in PPACK. In this study, using PPACK anticoagulant, selatogrel and zalunfiban affected PS in response to ADP equivalently at all drug concentrations tested. In contrast, zalunfiban had significantly greater potency at its Cmax concentration compared to selatogrel using TRAP as agonist. Upon evaluation of MA responses at lower doses, selatogrel had greater inhibition of MA in response to ADP than zalunfiban; however, at concentrations that represent Cmax, the drugs were equivalent. Zalunfiban also had greater inhibition of MA in response to TRAP at the Cmax dose. These data suggest that zalunfiban may provide greater protection in reducing thrombus formation than selatogrel, especially since thrombin is an early, key primary agonist in the pathophysiology of thrombotic events. Key Points: Zalunfiban and selatogrel are effective inhibitors of ADP-induced platelet aggregation. Zalunfiban, compared to selatogrel, is a more potent inhibitor of TRAP-induced platelet aggregation. Zalunfiban and selatogrel pharmacodynamics should be evaluated in PPACK anticoagulant when using ADP as the agonist. Additionally, zalunfiban pharmacodynamics can also be evaluated in 3.2% TSC for MA only when using TRAP as the agonist. Zalunfiban may provide greater protection in reducing thrombus formation, since thrombin is an early agonist in the pathophysiology of thrombotic events. [ABSTRACT FROM AUTHOR]

Platelets (PLTs) are believed to play a role in the process by which tumors can accelerate their growth rate, as well as offer the physical and mechanical support necessary to evade the immunological system and metastasis. There is, however, no literature available if PLTs have a role in leukemia. It is significant for PLTs to play a part in hematological malignancies from a therapeutic standpoint and to have the capacity to serve as a prognostic marker in the evolution of leukemia. This is because PLTs play a crucial role in the development of cancer and tumors. In this study, it will be shown that PLT count can be used to predict long-term prognosis after chemotherapy especially in the case of acute myeloid leukemia patients. Furthermore, low PLT-to-lymphocyte ratio and mean PLT volume, as well as high PLT distribution width, are associated with poor prognosis and may represent a novel independent prognostic factor. [ABSTRACT FROM AUTHOR]

Introduction: Acetaminophen (APAP) toxicity remains a significant cause of adult and pediatric liver failure in North America and Europe. Previous research has evaluated the impaired mitochondrial function associated with APAP toxicity. The primary aim of this study was to evaluate the effects of APAP toxicity on platelet mitochondrial function using platelet oxygen consumption in a murine model in vivo. Our secondary objectives were to determine the effect of 4-MP on platelet mitochondrial function and hepatic toxicity in the setting of APAP overdose, and to correlate platelet mitochondrial function with other markers of APAP toxicity. Methods: Male C57Bl/6 mice were randomized to receive APAP (300 or 500 mg/kg) or vehicle followed 90 minutes later by either 4-MP (50 mg/kg) or vehicle via intraperitoneal injection. Mice were euthanized 0, 12, or 24 hours later and platelets isolated from cardiac blood and counted. Platelet oxygen consumption (POC) was determined using a closed-system respirometer. Liver injury was assessed by measuring alanine transferase (ALT) and histological evaluation. Results: Injection of 500 mg/kg APAP led to increased POC versus pair-matched control (vehicle) (p < 0.001). Administration of 4-MP did not affect POC in control or 300 mg/kg APAP mice. In mice receiving 500 mg/kg APAP and 4-MP, POC decreased significantly compared to mice receiving 500 mg/kg APAP alone (p < 0.01). Serum and histological analysis confirmed APAP-induced hepatic damage in mice receiving 500 mg/kg APAP and these effects blunted by treatment with 4-MP. Conclusions: Platelet oxygen consumption as a measure of mitochondrial function may be useful as a biomarker of hepatic APAP toxicity in the setting of moderate to severe overdose. Treatment with 4-MP decreases hepatic necrosis and may mitigate the harmful effects of APAP on platelet mitochondrial function detected via POC. [ABSTRACT FROM AUTHOR]

Platelets undergo remarkable morphological changes during storage. Platelets change into different sizes and densities and differ in their biochemistry and functions. However, the correlation between structural heterogeneity and platelet autophagy is largely unknown. The aim of this study was to investigate the autophagy process in vitro, such as routine storage of platelets, and explore the role of reactive oxygen species (ROS) involved in the regulation of platelet autophagy. The ROS and autophagy levels of platelet concentrates from apheresis platelets were evaluated through flow cytometry. The expression levels of autophagy-associated proteins (LC3I, LC3II, Beclin1, Parkin, and PINK1) were measured via Western blot. All biomarkers were dynamically monitored for seven days. Moreover, the morphological characteristics of platelet morphology during storage were analyzed through transmission electron microscopy (TEM). Flow cytometry showed that the levels of total cell ROS and mitochondria ROS increased in the stored platelets. Together with the increase in mitochondrial ROS, the autophagy signal LC3 in the platelets was strongly amplified. The number of swollen platelets (large platelets) considerably increased, and that of autophagy signal LC3 was remarkably higher than that of the normal platelets. Western blot revealed that the expression levels of Beclin1 and LC3 II/LC3 I ratio were enhanced, whereas those of Parkin and PINK1 almost did not change during the seven days of storage. The existence of autophagosomes or autophagolysosomes in the platelets at the middle stage of platelet storage was observed via TEM. Our data demonstrated that the subpopulation of large (swollen) platelets exhibited different autophagy patterns. Furthermore, increased platelet autophagy was associated with mitochondrial ROS. These preliminary results suggest that swelling platelets have a higher autophagy pattern than normal platelets during storage. [ABSTRACT FROM AUTHOR]

Primary immune thrombocytopenia (ITP) is an autoimmune condition that results in a decreased number of platelets in the bloodstream. In human beings, platelet production is primarily promoted by thrombopoietin (TPO). However, the administration of recombinant human thrombopoietin (rh-TPO) requires daily injections and has a low response rate. To overcome this limitation, researchers have developed a thrombopoietin mimic peptide (TMP), which has the ability to attach to and stimulate the TPO receptor, thereby preventing the production of neutralizing antibodies against TPO. Unfortunately, TMP has a short half-life, which hinders its clinical use. In this study, we aimed to address this issue by designing a novel long-acting TMP fusion protein utilizing HSA-binding designed ankyrin repeat proteins (DARPins) as a carrier. The fusion protein, dTMP-DARPin, was created by genetically fusing tandem TMPs to the N-terminus of HSA-binding DARPins using a linker. The fusion protein of dTMP-DARPin was effectively produced in a soluble state within Escherichia coli and later purified using affinity chromatography. In vivo bioactivity experiments demonstrated that the dTMP-DARPin fusion protein effectively stimulated platelet proliferation in mice, leading to a more than two-fold increase in platelet count compared to TMP dimer (dTMP) alone. This increase in platelet count persisted for 15 days following injection, significantly longer than when using dTMP alone. The half-life of dTMP-DARPin in mice was measured to be 31.6 ± 5.8 h, approximately 32 times longer than that of dTMP. Consequently, the long-acting dTMP-DARPin fusion protein exhibits substantial bioactivity in promoting platelet formation in vivo and holds considerable promise for the treatment of ITP in the future. Moreover, the use of HSA-binding DARPins as a half-life extension carrier could potentially improve the pharmacokinetics of other peptide or protein drugs. [ABSTRACT FROM AUTHOR]

Many clinical features, besides cytogenetic and molecular abnormalities, can affect the prognosis of the patients with acute myeloid leukemia (AML). Within this context it remains unclear if and how platelet counts affect the outcome of AML patients. In the present study, we examined the platelet counts at diagnosis in 633 newly diagnosed adult patients with AML from January 2010 to April 2021, and divided the cases into the group with low level of platelet counts (≤30×109/L, n=316) and high level of platelet counts (>30×109/L, n=317) according to the median platelet counts. We then validated the prognostic significance and potential mechanism of platelet counts on the relevance of spectral features for diagnostic risk stratification, initial induction therapy response, treatment effect maintenance, long-term survival, leukemia stem cells (LSCs) proportion, immunomodulatory cytokines level and immune cell subsets proportion. The results suggested that AML patients with a high level of platelet counts at diagnosis were associated with a high-risk molecular cytogenetic stratification, low complete remission (CR) rate, poor leukemia free survival (LFS), high proportion of LSCs, high level of transforming growth factor-β (TGF-β) and interleukin-1β (IL-1β), high proportion of regulatory T cells (Tregs) and monocytic myeloid-derived suppressor cells (M-MDSCs). It was demonstrated that platelet might be an unfavorable prognostic biomarker and was associated with LSCs and immunomodulatory cytokines as well as immune cell subsets in AML. [ABSTRACT FROM AUTHOR]

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Deep venous thrombosis is a frequent, multifactorial disease and a leading cause of morbidity and mortality. Most of the time deep venous thrombosis is triggered by the interaction between acquired risk factors, such as hip fracture, pregnancy, and immobility, and hereditary risk factors such as thrombophilias. The mechanisms underlying deep venous thrombosis are not fully elucidated; however, in recent years, important advances have shed light on the role of venous flow, endothelium, platelets, leukocytes, and the interaction between inflammation and hemostasis. It has been described that the alteration of venous blood flow produces endothelial activation, favoring the adhesion of platelets and leukocytes, which, through tissue factor expression and neutrophil extracellular traps formation, contribute to the activation of coagulation, trapping more cells, such as red blood cells. Thus, the concerted interaction of these phenomena allows the formation and growth of the thrombus. In this work, the main mechanisms involved in the pathophysiology of deep vein thrombosis will be described. [ABSTRACT FROM AUTHOR]

Purpose: We previously showed that the crosstalk of H1975 cells and platelets (PLTs) may promote tumor angiogenesis. This study aimed to determine whether other lung cell lines (LC) interacting with PLTs could affect tumor angiogenesis through in vivo and in vitro experiments. Methods: Cell Counting Kit-8, EdU cell proliferation, wound healing, Transwell invasion, F-actin staining, tube formation, ELISA and western blot assays were performed to investigate the properties and the expression levels of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), p-VEGFR2, PI3K, p-PI3K, Akt, p-Akt and eNOS in supernatants or HUVECs. Then, using mouse models, immunohistochemistry was applied to detect the expression levels of CD31 and VEGF. Results: Compared with single-cultured HUVECs (EC) or incubation with either LC supernatant (EC + LC) or activated PLT supernatant (EC + PLT), incubation with SN_LCP (supernatant derived from LC cocultured with PLT, named the EC + LC + PLT group) improved the viability, proliferation, migration, invasion, and tube formation activities of HUVECs and the expression of F-actin, VEGF, VEGFR2, p-VEGFR2, p-PI3K, p-Akt and eNOS in HUVECs. Higher expression levels of CD31 and VEGF were found in the LLC + PLT (mouse model inoculated with Lewis lung cancer (LLC) cells cocultured with PLTs) group than in the LLC (mouse model inoculated with LLC cells alone) group. However, the increased angiogenic properties of HUVECs were inhibited by apatinib, an inhibitor of VEGFR2. Conclusion: Lung carcinoma cells interacting with PLTs may play a key role in lung carcinoma angiogenesis through the VEGF/VEGFR2 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Hyperreactive platelets are commonly observed in diabetic patients indicating a potential link between glucose homeostasis and platelet reactivity. This raises the possibility that platelets may play a role in the regulation of metabolism. Pancreatic β cells are the central regulators of systemic glucose homeostasis. Here, we show that factor(s) derived from β cells stimulate platelet activity and platelets selectively localize to the vascular endothelium of pancreatic islets. Both depletion of platelets and ablation of major platelet adhesion or activation pathways consistently resulted in impaired glucose tolerance and decreased circulating insulin levels. Furthermore, we found platelet‐derived lipid classes to promote insulin secretion and identified 20‐Hydroxyeicosatetraenoic acid (20‐HETE) as the main factor promoting β cells function. Finally, we demonstrate that the levels of platelet‐derived 20‐HETE decline with age and that this parallels with reduced impact of platelets on β cell function. Our findings identify an unexpected function of platelets in the regulation of insulin secretion and glucose metabolism, which promotes metabolic fitness in young individuals.

Abstract Thromboinflammation is the major cause of morbidity and mortality in COVID‐19 patients, and post‐mortem examination demonstrates the presence of platelet‐rich thrombi and microangiopathy in visceral organs. Moreover, persistent microclots were detected in both acute COVID‐19 and long COVID plasma samples. However, the molecular mechanism of SARS‐CoV‐2‐induced thromboinflammation is still unclear. We found that the spleen tyrosine kinase (Syk)‐coupled C‐type lectin member 2 (CLEC2), which was highly expressed in platelets and alveolar macrophages, interacted with the receptor‐binding domain (RBD) of SARS‐CoV‐2 spike protein (SARS‐CoV‐2 RBD) directly. Unlike the thread‐like NETs, SARS‐CoV‐2‐induced aggregated NET formation in the presence of wild‐type (WT), but not CLEC2‐deficient platelets. Furthermore, SARS‐CoV‐2 spike pseudotyped lentivirus was able to induce NET formation via CLEC2, indicating SARS‐CoV‐2 RBD engaged CLEC2 to activate platelets to enhance NET formation. Administration of CLEC2.Fc inhibited SARS‐CoV‐2‐induced NET formation and thromboinflammation in AAV‐ACE2‐infected mice. Thus, CLEC2 is a novel pattern recognition receptor for SARS‐CoV‐2, and CLEC2.Fc and may become a promising therapeutic agent to inhibit SARS‐CoV‐2‐induced thromboinflammation and reduced the risk of post‐acute sequelae of COVID‐19 (PASC) in the future.

Arterial baroreflex (ABR) dysfunction has previously been associated with neuroinflammation, the most common pathological feature of neurological disorders. However, the mechanisms mediating ABR dysfunction-induced neuroinflammation are not fully understood. In the present study, we investigated the role of platelet CD40 ligand (CD40L) in neuroinflammation in an in vivo model of ABR dysfunction, and microglia and astrocyte activation in vitro. ABR dysfunction was induced in Sprague‒Dawley rats by sinoaortic denervation (SAD). We used ELSA and immunofluorescence to assess the effect of platelet CD40L on glial cell polarization and the secretion of inflammatory factors. By flow cytometry, we found that rats subjected to SAD showed a high level of platelet microaggregation and upregulation of CD40L on the platelet surface. The promotion of platelet invasion and accumulation was also observed in the brain tissues of rats subjected to SAD. In the animal model and cultured N9 microglia/C6 astrocytoma cells, platelet CD40L overexpression promoted neuroinflammation and activated M1 microglia, A1 astrocytes, and the nuclear factor kappa B (NFκB) signaling pathway. These effects were partially blocked by inhibiting platelet activity with clopidogrel or inhibiting CD40L-mediated signaling. Our results suggest that during ABR dysfunction, CD40L signaling in platelets converts microglia to the M1 phenotype and astrocytes to the A1 phenotype, activating NFκB and resulting in neuroinflammation. Thus, our study provides a novel understanding of the pathogenesis of ABR dysfunction-induced neuroinflammation and indicates that targeting platelet CD40L is beneficial for treating central nervous system (CNS) disorders associated with ABR dysfunction. [ABSTRACT FROM AUTHOR]

Rise in the incidences of chronic degenerative diseases with aging makes wound care a socio-economic burden and unceasingly necessitates a novel, economical, and efficient wound healing treatment. Platelets have a crucial role in hemostasis and thrombosis by modulating distinct mechanistic phases of wound healing, such as promoting and stabilizing the clot. Platelet-rich plasma (PRP) contains a high concentration of platelets than naïve plasma and has an autologous origin with no immunogenic adverse reactions. As a consequence, PRP has gained significant attention as a therapeutic to augment the healing process. Since the past few decades, a robust volume of research and clinical trials have been performed to exploit extensive role of PRP in wound healing/tissue regeneration. Despite these rigorous studies and their application in diversified medical fields, efficacy of PRP-based therapies is continuously questioned owing to the paucity of large samplesizes, controlled clinical trials, and standard protocols. This review systematically delineates the process of wound healing and involvement of platelets in tissue repair mechanisms. Additionally, emphasis is laid on PRP, its preparation methods, handling, classification,application in wound healing, and PRP as regenerative therapeutics combined with biomaterials and mesenchymal stem cells (MSCs). [ABSTRACT FROM AUTHOR]

Despite years of encouraging translational research, ischemic stroke still remains as one of the highest unmet medical needs nowadays, causing a tremendous burden to health care systems worldwide. Following an ischemic insult, a complex signaling pathway emerges leading to highly interconnected thrombotic as well as neuroinflammatory signatures, the so-called thromboinflammatory cascade. Here, we thoroughly review the cell-specific and time-dependent role of different immune cell types, i.e., neutrophils, macrophages, T and B cells, as key thromboinflammatory mediators modulating the neuroinflammatory response upon stroke. Similarly, the relevance of platelets and their tight crosstalk with a variety of immune cells highlights the relevance of this cell-cell interaction during microvascular dysfunction, neovascularization, and cellular adhesion. Ultimately, we provide an up-to-date overview of therapeutic approaches mechanistically targeting thromboinflammation currently under clinical translation, especially focusing on phase I to III clinical trials. [ABSTRACT FROM AUTHOR]

Background: The predictive value of hematological markers in the outcomes after laparoscopic intraperitoneal onlay mesh repair (IPOM) remains to be investigated. We aim to evaluate the role of platelet-related parameters after laparoscopic IPOM in patients with incisional hernias. Methods: The data of 95 patients who underwent laparoscopic IPOM for appendicectomy-related incisional hernias were retrospectively analyzed. The complete blood count analyses were measured preoperatively, and the outcomes were obtained from hospital records and follow-up calls to patients. Platelet-multiple-lymphocyte index (PLM), neutrophil–leukocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), platelet–lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) values were calculated. The patients were grouped based on the recurrence and the postoperative complications after surgery. Results: Using cutoff values acquired by the Youden Index, we found platelet levels < 212.0 × 1000/μl, NLR > 2.33, LMR < 3.17, and PLM < 365.5 were revealed to be statistically significant in the recurrence of hernias based on univariant or multivariant analysis (p = < 0.05). We further divided the patients into two groups based on the cutoff value of PLM and found that a PLM value < 365.5 was significantly associated with the recurrence of incisional hernia (p = 0.018), the occurrence of postoperative seroma (p = 0.044), and there is a tendency that patients with PLM < 365.5 may suffer from other postoperative complications such as cardiopathy, respiratory infection, and hypoproteinemia (p = 0.089). Conclusion: The preoperative hematological values, especially PLM, may indicate the outcomes in incisional hernias after laparoscopic IPOM. [ABSTRACT FROM AUTHOR]

Background: Whether insulin resistance underlies deep venous thrombosis (DVT) development in patients with severe traumatic brain injury (TBI) is unclear. In this study, the association between plasma insulin levels and DVT was analyzed in patients with severe TBI. Methods: A prospective observational study of 73 patients measured insulin, glucose, glucagon-like peptide 1 (GLP-1), inflammatory factors, and hematological profiles within four preset times during the first 14 days after TBI. Ultrasonic surveillance of DVT was tracked. Two-way analysis of variance was used to determine the factors that discriminated between patients with and without DVT or with and without insulin therapy. Partial correlations of insulin level with all the variables were conducted separately in patients with DVT or patients without DVT. Factors associated with DVT were analyzed by multivariable logistic regression. Neurological outcomes 6 months after TBI were assessed. Results: Among patients with a mean (± standard deviation) age of 53 (± 16 years), DVT developed in 20 patients (27%) on median 10.4 days (range 4–22), with higher Acute Physiology and Chronic Health Evaluation II scores but similar Sequential Organ Failure Assessment scores and TBI severity. Patients with DVT were more likely to receive insulin therapy than patients without DVT (60% vs. 28%; P = 0.012); hence, they had higher 14-day insulin levels. However, insulin levels were comparable between patients with DVT and patients without DVT in the subgroups of patients with insulin therapy (n = 27) and patients without insulin therapy (n = 46). The platelet profile significantly discriminated between patients with and without DVT. Surprisingly, none of the coagulation profiles, blood cell counts, or inflammatory mediators differed between the two groups. Patients with insulin therapy had significantly higher insulin (P = 0.006), glucose (P < 0.001), and GLP-1 (P = 0.01) levels and were more likely to develop DVT (60% vs. 15%; P < 0.001) along with concomitant platelet depletion. Insulin levels correlated with glucose, GLP-1 levels, and platelet count exclusively in patients without DVT. Conversely, in patients with DVT, insulin correlated negatively with GLP-1 levels (P = 0.016). Age (P = 0.01) and elevated insulin levels at days 4–7 (P = 0.04) were independently associated with DVT. Patients with insulin therapy also showed worse Glasgow Outcome Scale scores (P = 0.001). Conclusions: Elevated insulin levels in the first 14 days after TBI may indicate insulin resistance, which is associated with platelet hyperactivity, and thus increasing the risk of DVT. [ABSTRACT FROM AUTHOR]

Platelet-derived microvesicles (PMVs), the microvesicles with the highest concentration in the bloodstream, play a key role in the regulation of hemostasis, inflammation, and angiogenesis. PMVs have recently been identified as key factors in the link between platelets and cancer. PMVs bind to both cancer cells and nontransformed cells in the microenvironment of the tumor, and then transfer platelet-derived contents to the target cell. These contents have the potential to either stimulate or modulate the target cell's response. PMVs are encased in a lipid bilayer that contains surface proteins and lipids as well as components found inside the PMV. Each of these components participates in known and potential PMV roles in cancer. The complicated roles played by PMVs in the onset, development, and progression of cancer and cancer-related comorbidities are summarized in this study. [ABSTRACT FROM AUTHOR]

Recently, one of the main tasks of blood transfusion agencies is to monitor blood products such as platelets, plasma proteins, and red blood cells to achieve the right conditions for their storage and safety, such as reducing the transfusion-associated graft-versus-host disease and potential transmission of syphilis, economies of scale in testing, processing, collection, and development of quality control. Anticoagulants, storage temperature, and storage equipment influence blood products' storage performance and stability. Moreover, various methods enhance the storage and stability of blood products, such as automatic equipment and optimal conditions for complete blood collection, removing leukocytes from the blood components using filtration, centrifugation, and nanoparticles. It is worth noting that nanotechnology has been widely used in connection with blood and blood products such as anticoagulants, targeted drug delivery, sensors, imaging, storage, and transmission. Several studies have investigated the impact of different nanoparticles on blood products such as polymeric nanoparticles, non-metallic nanoparticles, and metal oxide nanoparticles. Recently, various nanopolymers such as dendrimers, polyethylene glycol, chitosan, lactic-co-glycolic acid, and liposomes have been used due to their ease of synthesis, biocompatibility, component diversity, and biodegradation conditions to improve the quality of blood products. To the best of our knowledge, there is no study reviewing the impact of polymeric nanoparticles in the field of blood products storage. Therefore, we aimed to provide an overview of polymeric nanoparticles' effects on enhancing blood products' storage quality and performance (red blood cells, plasma, and platelets). Here we concluded liposome nanoparticles are effective preservatives for RBCs during hypothermal conditions. Using negatively charged nanoparticles with low molecular weight can increase the storage time of platelets. In contrast, positively charged nanoparticles harm RBCs and platelets by inducing RBC rupture and platelets aggregation. Chitosan nanoparticles, liposomes, and lipid nanoparticles were also introduced as stabilizing agents to enhance albumin quality, immunoglobulins, and factor VIII, respectively. [ABSTRACT FROM AUTHOR]

In addition to the key role in hemostasis and thrombosis, platelets have also been wildly acknowledged as immune regulatory cells and involving in the pathogenesis of inflammation-related diseases. Since purine receptor P2Y12 plays a crucial role in platelet activation, P2Y12 antagonists such as clopidogrel, prasugrel, and ticagrelor have been widely used in cardiovascular diseases worldwide in recent decades due to their potent antiplatelet and antithrombotic effects. Meanwhile, the role of P2Y12 in inflammatory diseases has also been extensively studied. Relatively, there are few studies on the regulation of P2Y12. This review first summarizes the various roles of P2Y12 in the process of platelet activation, as well as downstream effects and signaling pathways; then introduces the effects of P2Y12 in inflammatory diseases such as sepsis, atherosclerosis, cancer, autoimmune diseases, and asthma; and finally reviews the current researches on P2Y12 regulation. [ABSTRACT FROM AUTHOR]

Purpose: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. Methods: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. Results: The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. Conclusions: Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384. [ABSTRACT FROM AUTHOR]

Rationale: Assessment of the bioeffect of serotonin reuptake inhibitors (SRIs, including both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)) at the serotonin transporter (SERT) in patients and healthy controls can have important theoretical and clinical implications. Objectives: Bioeffect at SERT has been assessed by neuroimaging of brain SERT occupancy, through in vitro measurements of platelet serotonin (5-HT) uptake, and by measuring platelet 5-HT content pre- and post-initiation of SRI administration. Studies of platelet 5-HT content were reviewed in order to (1) determine the overall apparent bioeffect of SRIs; (2) compare bioeffect across types of SRIs; (3) compare the three approaches to assessing SRI bioeffect; and (4) determine how the findings might inform clinical practice. Methods: We performed a systematic review of the published studies that measured platelet 5-HT content to assess SRI bioeffect at the platelet SERT. Studies using neuroimaging and in vitro platelet 5-HT uptake to assess SRI bioeffect were reviewed for comparison purposes. Results: Clinical doses of SRIs typically resulted in 70–90% reductions in platelet 5-HT content. The observed bioeffect at the platelet SERT appeared similar among different SSRIs and SNRIs. The bioeffect estimations based on platelet 5-HT content were consistent with those obtained using neuroimaging to assess brain SERT occupancy and those based on the in vitro measurement of platelet 5-HT uptake. Conclusions: In general, excellent agreement was seen in the apparent SRI bioeffect (70–90% inhibition) among the platelet 5-HT content studies and across the three bioeffect approaches. Theoretical and practical clinical implications are discussed. [ABSTRACT FROM AUTHOR]

In this study, we present a method to quantitatively analyze the thrombus formation process through image analysis in an in vitro thrombus model with a circular cross section. The thrombus model used was designed based on the mechanism between the physical principle of wall shear rate (WSR) and thrombus formation. Image analysis was used to help visualize the thrombus formation process and calculate the thrombus area. Through this method, the thrombus formation and growth from the channel wall was demonstrated without the use of fluorescence. In addition, by dividing the image into sub-sections, the accuracy of the thrombus growth pattern was improved. The departing blood clots which are called embolus, were observed being separated from the thrombus. [ABSTRACT FROM AUTHOR]