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Backgrounds/Objectives: Abnormal platelet functions are associated with human morbidity and mortality. Platelets have emerged as critical regulators of numerous physiological and pathological processes beyond their established roles in hemostasis and thrombosis. Maintaining physiological platelet function is essential to hemostasis and preventing platelet-associated diseases such as cardiovascular disease, cancer metastasis, immune disorders, hypertension, diabetes, sickle cell disease, inflammatory bowel disease, sepsis, rheumatoid arthritis, myeloproliferative disease, and Alzheimer's disease. Platelets become hyperactive in obesity, diabetes, a sedentary lifestyle, hypertension, pollution, and smokers. Platelets, upon activation, can trawl leukocytes and progenitor cells to the vascular sites. Platelets release various proinflammatory, anti-inflammatory, and angiogenic factors and shed microparticles in the circulation, thus promoting pathological reactions. These platelet-released factors also maintain sustained activation, further impacting these disease processes. Although the mechanisms are unknown, multiple stimuli induce platelet hyperreactivity but involve the early pathways of platelet activation. The exact mechanisms of how hyperactive platelets contribute to these diseases are still unclear, and antiplatelet strategies are inevitable for preventing these diseases. Reducing platelet function during the early stages could significantly impact these diseases. However, while this is potentially a worthwhile intervention, using antiplatelet drugs to limit platelet function in apparently healthy individuals without cardiovascular disease is not recommended due to the increased risk of internal bleeding, resistance, and other side effects. The challenge for therapeutic intervention in these diseases is identifying factors that preferentially block specific targets involved in platelets' complex contribution to these diseases while leaving their hemostatic function at least partially intact. Since antiplatelet drugs such as aspirin are not recommended as primary preventives, it is essential to use alternative safe platelet inhibitors without side effects. Methods: A systematic search of the PUBMED database from 2000 to 2023 was conducted using the selected keywords: "functional foods", "polyphenols", "fatty acids", "herbs", fruits and vegetables", "cardioprotective agents", "plant", "platelet aggregation", "platelet activation", "clinical and non-clinical trial", "randomized", and "controlled". Results: Potent natural antiplatelet factors have been described, including omega-3 fatty acids, polyphenols, and other phytochemicals. Antiplatelet bioactive compounds in food that can prevent platelet hyperactivity and thus may prevent several platelet-mediated diseases, including cardiovascular disease. Conclusions: This narrative review describes the work during 2000–2023 in developing functional foods from natural sources with antiplatelet effects. [ABSTRACT FROM AUTHOR]

Background and Aims: Blood, vital for transporting nutrients and maintaining balance, comprises red blood cells, white blood cells, and platelets, each pivotal. Imbalances lead to issues—low red cells cause fatigue (anemia), high white cells hint at infection, low counts raise infection risks. Using trendy statistical approaches, investigating the complex link between platelet counts and numerous blood components. Our investigation, leveraging count regression approaches, revealed deep insights into the interaction between platelet counts and other important hematological markers. Methods: A cross‐sectional study utilized data from 3120 individuals, including both male and female participants, who visited these hospitals between June 16, 2022 and December 17, 2022, to assess their blood samples through testing by using convenience non‐parametric sampling framework. Platelet count was taken into account as a measure of outcome in this research. This specific study region was chosen for its easy accessibility, which helped the seamless execution of the data‐gathering technique. Count regression, negative binomial regression, and quasi‐Poisson regression techniques have been employed for examining relationship of the data sets. Results: Three different count regression models were utilized to assess the proper association between the response and the relevant covariates and we found negative binomial count regression model (Akaike information criterion = 76.55, Bayesian information criterion = 76.59, and deviance = 3.14) was providing comparatively better performance than others. Based on the chosen model we found white blood cell, erythrocyte sedimentation rate, and eosinophils are significant but neutrophil, monocyte, and lymphocyte are not significant. We have also gone through proper model adequacy checking for our selected model and we found enough evidence to justify our model. Conclusion: From the result, we found insightful remarks into the mechanisms involved in platelet production and regulation, which can aid in developing increased effective treatments and interventions to maintain optimal platelet levels and prevent health problems related to abnormal platelet counts. [ABSTRACT FROM AUTHOR]

Background Diabetes mellitus is a group of chronic metabolic diseases with increased blood sugar. In various studies, the association between diabetes and hematologic parameters has been investigated. Diabetes mellitus may lead to different hematologic abnormalities. Objective A complete blood cell count is more available than hemoglobin A1C, in this study we summarize the hematologic changes in type 1 diabetes. The reasons and association of different changes with the prognosis will be discussed. Methods This study is a review article based on a search with the keywords in medical-scientific databases, including PubMed, Scopus, MEDLINE, and Google Scholar, from 2000 to 2023. All articles were evaluated, and 50 articles were selected as the primary study sources. Results The mean of red blood cell count, hemoglobin, and hematocrit were less in the diabetic group in comparison to healthy patients. Recent studies show an association between anemia and with development of diabetic nephropathy. Diabetic patients have higher red cell distribution width compared to healthy individuals. Mean platelet volume and platelet distribution width are higher in children with type I diabetes compared to healthy children. Studies showed that patients who have recently been diagnosed with type 1 diabetes mellitus have higher leukocyte and neutrophil counts. Also, there is a positive correlation between increased leukocyte and hyperglycemia. Conclusion The occurrence of blood cell changes in children with type 1 diabetes is related to the prognosis of the disease. Since hematological tests (complete blood cell count) are available, the use of these tests is helpful for early detection of complications [ABSTRACT FROM AUTHOR]

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants—genipin, patent blue V, and brilliant blue FCF—on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1–200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well. [ABSTRACT FROM AUTHOR]

ObjectiveTo explore the correlation between platelet-to-lymphocyte ratio (PLR) and failed treatment in patients with peritoneal dialysis-associated peritonitis (PDAP).MethodsFrom January 2018 to October 2022, 136 hospitalized patients fulfilling the clinical diagnostic criteria of PDAP were selected as study subjects. Demographic profiles, clinical examinations and laboratory parameters were recorded. They were assigned into two groups of successful treatment and failed treatment. General profiles and relevant clinical data of two groups were compared. The relationship between PLR and failed treatment of PDAP was examined by multivariate Logistic regression analysis. And receiver operating characteristic (ROC) curve was plotted for examining the predictive value of PLR on failed treatment of PDAP.ResultsA total of 221 bouts of PDAP occurred in 136 PD patients. As compared with successful treatment group, the levels of PLR[（472 ± 296） vs （232 ± 106）], NLR[（15.40 ± 11.20） vs （7.49 ± 5.92）] and platelet[（256 ± 92）×109/L vs （ 216 ± 84）×109/L] spiked markedly in failed treatment group. There were statistically significant differences (P

Abstract Background and Aims Blood, vital for transporting nutrients and maintaining balance, comprises red blood cells, white blood cells, and platelets, each pivotal. Imbalances lead to issues—low red cells cause fatigue (anemia), high white cells hint at infection, low counts raise infection risks. Using trendy statistical approaches, investigating the complex link between platelet counts and numerous blood components. Our investigation, leveraging count regression approaches, revealed deep insights into the interaction between platelet counts and other important hematological markers. Methods A cross‐sectional study utilized data from 3120 individuals, including both male and female participants, who visited these hospitals between June 16, 2022 and December 17, 2022, to assess their blood samples through testing by using convenience non‐parametric sampling framework. Platelet count was taken into account as a measure of outcome in this research. This specific study region was chosen for its easy accessibility, which helped the seamless execution of the data‐gathering technique. Count regression, negative binomial regression, and quasi‐Poisson regression techniques have been employed for examining relationship of the data sets. Results Three different count regression models were utilized to assess the proper association between the response and the relevant covariates and we found negative binomial count regression model (Akaike information criterion = 76.55, Bayesian information criterion = 76.59, and deviance = 3.14) was providing comparatively better performance than others. Based on the chosen model we found white blood cell, erythrocyte sedimentation rate, and eosinophils are significant but neutrophil, monocyte, and lymphocyte are not significant. We have also gone through proper model adequacy checking for our selected model and we found enough evidence to justify our model. Conclusion From the result, we found insightful remarks into the mechanisms involved in platelet production and regulation, which can aid in developing increased effective treatments and interventions to maintain optimal platelet levels and prevent health problems related to abnormal platelet counts.

Introduction: Delayed graft function (DGF), an outcome for which inflammation is critical, has been associated with worse outcomes after kidney transplantation (KT). The neutrophil to lymphocyte and platelet (NLP) ratio is a biomarker of systemic inflammation. We assessed postoperative NLP ratio applicability as an early predictor of DGF in KT patients. Methods: Retrospective cohort of adult patients submitted to KT at our unit, between 1 January 2010 and 31 December 2020. NLP was calculated at 24 hours post-KT. Primary outcome was development of DGF. Logistic regression was calculated to determine significant factors which may have contributed to DGF. Results: We included 527 patients with a mean age of 49.9 ± 12.8 years. In 47.8% of patients expanded criteria donors were used, and in 3.6% non-heart-beating donors. DGF occurred in 17.8% of patients. Mean post-KT NLP was higher in patients submitted to induction therapy with lymphocyte depleting antibodies (50.2±40.3 vs 11.9±7.4 with basiliximab, p

Objectives: The impact of COVID-19 prompted a race to find a treatment that would reduce its mortality. This study aimed to analyze how the clinical and laboratory characteristics reflect the disease process and progression of COVID-19 cases in hospitalized patients of Mongolia, which could be informative in managing patients with COVID-19. Methods: A cross-sectional study was conducted on the prescription patterns of drugs given to hospitalized patients diagnosed with COVID-19. A total of 1012 participants were recruited in the study. These were identified from the reported positive cases by polymerase chain reaction or antigen reactivity performed in Ulaanbaatar. Result: A total of 1096 patients participated in this study. The mean age was 51.86 ± 16.98 for male patients and 52.23 ± 16.4 for female patients. It has been revealed that there are statistically significant differences between male and female patients. RBC was 4.56 ± 0.79 M/ UL and 5.08 ± 1.36 M/UL, men and women respectively. The levels of C-reactive protein (CRP) in female COVID-19 patients were significantly higher (46.75 ± 72.83 mg/dL) compared to male patients (33.94 ± 47.96 mg/dL). The platelet count (PLT) was 245.32 ± 77.71 for male patients, while there was a significant reduction in PLT count in female patients (229.30 ± 71.59). Conclusions: Patients with COVID-19 in Mongolia appeared to remain in the hospital for 6.86 ± 2.43 days, shorter than in other countries. Hematological analysis showed that female patients had elevated C-reactive protein levels and decreased PLT count.

Background: In 15% of all clinical pregnancies, a miscarriage can occur, but the exact cause of this phenomenon is not fully understood. However, it is believed that a faulty placenta, which triggers an inflammatory response in the mother's body, may be one of the causes. Medical literature has increasingly focused on 2 indicators of inflammation, the plateletlymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR). Despite this, there has yet to be a study conducted that examines the rates of PLR and NLR in cases of miscarriage. Objective: This study aims to determine whether there is an increase in complete blood count inflammatory parameters such as NLR and PLR in women who experience miscarriages. Materials and Methods: This retrospective case-control study was conducted from March 2021 to March 2022, across 3 academic hospitals in Tehran, Iran. A total of 240 participants were enrolled comprising individuals with either miscarriages or normal pregnancies (n = 120/each). Data were collected from the medical records of participants aged between 18-42 yr old, with gestational age ranging from 6-13 wk. The demographic information, including age, body mass index, parity, history of abortion, number of abortions, number of living children, hematocrit and hemoglobin levels, platelet distribution width (PDW), PLR, NLR, mean platelet volume, and platelet were extracted from their records. The gestational age was also recorded. Results: A total of 240 participants were recruited for the study. PDW, NLR, PLR, and lymphocyte values were higher in the miscarriage group compared to the healthy normal pregnant women (p < 0.001). Mean platelet volumes were found to be lower in the miscarriage group compared to the healthy normal pregnant women (p < 0.001). Conclusion: Although, no statistically significant difference was observed in the hemoglobin, hematocrit, platelets, and neutrophils in these 2 groups of pregnant women. The higher inflammatory markers including PDW, NLR, and PLR could potentially aid in the speculation of defective placentation as a contributing factor to the development of miscarriage. Measurement of these markers may be useful to predict pregnancy leading to miscarriage. [ABSTRACT FROM AUTHOR]

The current study evaluated the healing of critical-size defects (CSD) created in rat calvaria treated with platelet concentrates produced by high-speed (Leukocyte- and Platelet-Rich Fibrin - L-PRF) and low-speed (Advanced Platelet-Rich Fibrin - A-PRF) protocols of centrifugation. Twenty-four rats were distributed into three groups: Control, L-PRF, and A-PRF. Five mm diameter CSD were created on the animals’ calvaria. The defects of the L-PRF and A-PRF groups were filled with 0.01 ml of L-PRF and A-PRF, respectively. The control group defects were filled with a blood clot only. All animals were euthanized on the 35th postoperative day. Histomorphometric and microtomographic analyses were then performed. The L-PRF and A-PRF groups had significantly higher bone volume and neoformed bone area than those of the control group and lowered bone porosity values (p

Background Appropriate treatment of pulmonary hypertension (PH) is critically dependent on accurate discrimination between pre‐ and postcapillary PH. However, clinical discrimination is challenging and frequently requires a right heart catheterization. Existing risk scores to detect postcapillary PH have suboptimal discriminatory strength. We have previously shown that platelet‐derived RNA profiles may have diagnostic value for PH detection. Here, we hypothesize that platelet‐derived RNAs can be employed to select unique biomarker panels for the discrimination between pre‐ and postcapillary PH. Methods and Results Blood platelet RNA from whole blood was isolated and sequenced from 50 patients with precapillary PH (with different PH subtypes) as well as 50 patients with postcapillary PH. RNA panels were calculated by ANOVA statistics, and classifications were performed using a support vector machine algorithm, supported by particle swarm optimization. We identified in total 4279 different RNAs in blood platelets from patients with pre‐ and postcapillary PH. A particle swarm optimization–selected RNA panel of 1618 distinctive RNAs with differential levels together with a trained support vector machine algorithm accurately discriminated patients with precapillary PH from patients with postcapillary PH with 100% sensitivity, 60% specificity, 80% accuracy, and 0.95 (95% CI, 0.86–1.00) area under the curve in the independent validation series (n=20). Conclusions This proof‐of‐concept study demonstrates that particle swarm optimization/support vector machine–enhanced classification of platelet RNA panels may be able to discriminate precapillary PH from postcapillary PH. This research provides a foundation for the development of a blood test with a high negative predictive value that would improve early diagnosis of precapillary PH and prevents unnecessary invasive testing in patients with postcapillary PH.

The etiopathogenesis of retinal vein occlusion (RVO) is multifactorial, and the contribution of platelets to RVO development has not been fully elucidated. We aimed to analyze platelet function in RVO patients (n = 35) and controls (n = 35). We found a higher (p < 0.05) level of soluble P-selectin in RVO group vs. controls. Additionally, in RVO patients, the concentration of platelet-derived microvesicles was higher (p < 0.05), and the difference between groups was deeper for the fraction of platelet-derived microvesicles with the procoagulant phenotype (p < 0.0001) and for overall procoagulant microvesicles level (p < 0.0001). The results were similar for the total RVO group and for both RVO types (central- and branched-retinal vein occlusion). We did not find differences in simple platelet parameters (platelet count, mean platelet volume, platelet distribution width, platecrit, reticulated platelets) and inflammatory markers (platelet-lymphocyte ratio, neutrophil-lymphocyte ratio). Similarly, no differences were found for platelet aggregation-stimulated byadenosine diphosphate; collagen; arachidonic acid; and in multiparametric flow cytometry evaluation of P-selectin, PAC-1, and fibrinogen binding for both unstimulated and adenosine diphosphate-, collagen-, and thrombin receptor activating peptide-stimulated platelets. Our results suggest that platelets can contribute to developing RVO by enhancing procoagulant activity through providing a procoagulation surface via platelet-derived microvesicles. The direct role of platelets' hyperreactivity in developing RVO is less apparent, which is consistent with the complexity and multifactorial background of this disorder. [ABSTRACT FROM AUTHOR]

Introduction:Exercise can play a supportive role in the improvement of breast cancer by regulating and modulating cytokines. Interleukin 10 is an anti-inflammatory and anti-tumor cytokine that plays an important role in inhibiting tumor growth. This study was performed with aim to evaluate the effect of 12 weeks of combined exercise (aerobic_pilates) on the serum level of interleukin 10 and blood platelets in women with breast cancer. Methods: This experimental study was performed on 30 women with breast cancer who had undergone at least 6 months of surgery and had received chemotherapy and were under treatment with medication in Azarbaijan Shahid Madani University in 2019. The subjects were divided into experimental and control groups. The experimental group performed 3 sessions of exercise each week (aerobic-pilates) for 12 weeks. During this time, the control group did not participate in any exercise or physical activity program. Blood samples were obtained before and 48 hours after exercise intervention to extract the variables. Data were analyzed by SPSS software (version 20) and independent and correlated t-test. P 0.05). Conclusion: Performing combined exercises (aerobic_Pilates) by improving the status of interleukin 10 as an anti-inflammatory and anti-tumor cytokine can be useful in improving the health status of women with breast cancer. Therefore, designing and performing such exercises in this population can solve many problems of these loved ones.

Platelets are valuable, but highly perishable, blood components used in the treatment of, among others, viral dengue fever, blood-related illness, and post-chemotherapy following cancer. Given the short shelf-life of 3–5 days and a highly volatile supply and demand pattern, platelet inventory allocation is a challenging task. This is especially prevalent in emerging economies where demand variability is more pronounced due to neglected tropical diseases, and a perpetual shortage of supply. The consequences of which have given rise to an illegal 'red market'. Motivated by experience at a regional hospital in India, we investigate the problem of platelet allocation among three priority-differentiated demand streams. Specifically we consider a central hospital which, in addition to internal emergency and non-emergency requests, faces external demand from local clinics. We analyze the platelet allocation decision from a social planner's perspective and propose an allocation heuristic based on revenue management (RM) principles. The objective is to maximize total social benefit in a highly supply-constrained environment. Using data from the aforementioned Indian hospital as a case study, we conduct a numerical simulation and sensitivity analysis to evaluate the allocation heuristic. The performance of the RM-based policy is evaluated against the current sequential first come, first serve policy and two fixed proportion-based rationing policies. It is shown that the RM-based policy overall dominates, serves patients with the highest medical urgency better, and can curtail patients' need to procure platelets from commercial sources. [ABSTRACT FROM AUTHOR]

Abstract Background The contact factor XII (FXII) activates upon contact with a variety of charged surfaces. Activated FXII (FXIIa) activates factor XI, which activates factor IX, resulting in thrombin generation, platelet activation, and fibrin formation. In both in vitro and in vivo rabbit models, components of medical devices, including extracorporeal oxygenators, are known to incite fibrin formation in a FXII‐dependent manner. Since FXII has no known role in hemostasis and its inhibition is therefore likely a safe antithrombotic approach, we investigated whether FXII inhibition also reduces accumulation of platelets in extracorporeal oxygenators. Objectives We aimed to determine the effect of FXII inhibition on platelet deposition in perfused extracorporeal membrane oxygenators in nonhuman primates. Methods A potent FXII neutralizing monoclonal antibody, 5C12, was administered intravenously to block contact activation in baboons. Extracorporeal membrane oxygenators were temporarily deployed into chronic arteriovenous access shunts. Radiolabeled platelet deposition in oxygenators was quantified in real time using gamma camera imaging. Biochemical assays were performed to characterize the method of action of 5C12. Results The anti‐FXII monoclonal antibody 5C12 recognized both the alpha and beta forms of human and baboon FXII by binding to the protease‐containing domain, and inhibited FXIIa activity. Administration of 5C12 to baboons reduced platelet deposition and fibrin formation in the extracorporeal membrane oxygenators, in both the presence and absence of systemic low‐dose unfractionated heparin. The antiplatelet dose of 5C12 did not cause measurable increases in template bleeding times in baboons. Conclusions FXII represents a possible therapeutic and safe target for reducing platelet deposition and fibrin formation during medical interventions including extracorporeal membrane oxygenation.

The effect of dandelion root and its various ingredients on the biological functions of blood platelets has not been well investigated. Thus, the objective of our in vitro study was to examine the five root fractions (A–E), differing in chemical composition, for changes induced in the human platelets’ model using selected hemostatic parameters. As a result, the best anti-platelet potential was shown by preparation enriched with hydroxyphenylacaetate inositol esters – PIEs (fraction C). On the other hand, the best overall protective effect against oxidation of lipids and proteins of platelets, and the best inhibitory effect on the generation of O2−· were observed in the presence of fraction A (SL-amino acid adducts enriched fraction). Thus, PIEs and SLs rich plant organs, such as dandelion root, may be considered as potentially suitable additives for functional food products used in prophylaxis and treatment of cardiovascular diseases associated with hyperactivation of blood platelets.

Introduction. Congenital asplenia is an extremely rare condition that can be separate entity due to a specific defect of spleen development or may occur in the context of a malformation syndrome. The patients with asplenia have thrombocytosis and susceptibility to life-threatening infections. Case report. We report a 52-years-old female patient with isolated congenital asplenia with pseudothrombocytopenia and giant platelets. Estimation of platelets life with radioactive indium showed normal lenght of platelets life (9 days). Flow cytometric analysis of platelets showed normal expression of CD41 and CD42b antigens. The mean platelet diameter of asplenic patient measured on the ultrathin sections by the transmission electron microscope was significantly higher than in the healthy individuals (3.81 ± 1.16 μm vs. 2.37 ± 0.61 μm, p < 0.05). There were very few platelets of diameter more than 4 μm found in healthy individuals (around 1%) in comparison to > 40% of the patient’s platelets. The ultrastructural studies revealed normal morphology of megakaryocytes. The platelets were uniformly spheroid in shape with conspicuous pseudopodia and the centralization of granules. There were no marginal bands of microtubules inside the platelets. Conclusion. The first case of congenital asplenia with the pseudothrombocytopenia and giant platelets is presented. We discussed the pathogenesis of giant platelets and possible relation of observed ultrastructural changes of platelets with the severe three-vessel coronary artery disease in our patient.

Introduction: Tissue factor (TF) and factor (F) VII, components of the extrinsic pathway of blood coagulation, are essential for hemostatic plug formation in response to injury; less clear are their roles in propagating thrombosis, as observational data in humans with congenital FVII deficiency suggests persistent thrombotic and bleeding risk even at significantly decreased FVII levels. We aimed to define the contribution of FVII to thrombus formation and hemostasis using a non-human primate model. Methods: We treated baboons with a FVII antisense oligonucleotide (ASO) and measured platelet and fibrin deposition inside and distal to collagen- or TF-coated vascular grafts. We assessed hemostasis by measuring bleeding time (BT) and prothrombin time (PT). Enoxaparin and vehicle treatments served as controls. Results: FVII–ASO treatment reduced FVII levels by 95% and significantly increased both the PT and BT. Lowering FVII levels did not decrease platelet deposition in collagen- or TF-coated grafts, in thrombi distal to the grafts, or fibrin content of either collagen- and TF-coated grafts. Lowering FVII levels were associated with a modest 25% reduction in platelet deposition at 60 min in the distal thrombus tail of TF-coated grafts only. Conclusions: FVII inhibition by way of ASO is feasible yet significantly impairs hemostasis while only exhibiting antithrombotic effects when thrombosis is initiated by vessel wall surface-associated TF exposure. [ABSTRACT FROM AUTHOR]

Background: It is known that there is a definite association between platelet distribution width (PDW) and poor prognosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, there are no data available regarding the prognostic significance of PDW for in-stent restenosis (ISR) in patients with CAD and T2DM. We aimed to determine the value of PDW on admission that predicted ISR in patients with CAD and T2DM. Methods: Between January 2012 and December 2013, a total of 5232 consecutive patients diagnosed with CAD and T2DM undergoing percutaneous coronary intervention were admitted. Three years of retrospective follow-up was undertaken. A total of 438 patients with second angiography operations were included. ISR was defined as ≥50% luminal stenosis of the stent or peri-stent segments. Continuous data were presented as the mean ± standard deviation or median (P25, P75) and were compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical variables were presented as percentages and were compared by Chi-square test or Fisher's exact test. The association between PDW and ISR was calculated by logistic regression analysis. A two-sided value of P < 0.05 was considered statistically significant. Statistical analyses were performed by SPSS version 22.0 for windows. Results: Fifty-nine patients with ISR, accounting for 13.5% of the total, were included. ISR was significantly more frequent in patients with higher PDW quartiles compared with lower quartiles. We observed that PDW had a strong relationship with mean platelet volume (r = 0.647, 95% confidence interval [CI]: 0.535–0.750, P

BACKGROUND AND AIM: An important goal of periodontal plastic surgery is the creation of attached gingiva around the teeth. In this study, the aims were to culture gingival fibroblasts in a biodegradable scaffold and measure the width of attached gingiva after the clinical procedure. METHODS: This study was carried out on 4 patients (8 sites), with inadequate attached gingiva next to at least two teeth in contralateral quadrants of the same jaw. A biopsy of attached gingiva (epithelial + connective tissue) was taken using a surgical blade. Following culture of gingival fibroblasts, 250 × 103 cells in 250 µl nutritional medium were mixed with platelet-rich in growth factor (PRGF). Periosteal fenestration technique was done on one side (control) and tissue-engineered mucosal graft (test) was carried out on the contralateral side in each patient. The width of keratinized tissue, probing depth (PD) and width of attached gingiva were recorded at baseline and 3 months after the operation. RESULTS: An increased width of keratinized and attached tissue on all operated sites after 3 months was observed. These results showed the increased mean of the width of keratinized and attached gingiva to be 4.17 mm and 4.14 mm in test and 1.10 mm and 1.10 mm in control sites, respectively. The difference of keratinized and attached gingiva width between test and control sites was significant (P = 0.030, and P = 0.010 respectively). CONCLUSION: According to the results of this study, PRGF can be used as a scaffold to transfer gingival fibroblasts to recipient sites with significant clinical results.

Introduction: Type 2 diabetes mellitus, due to its high incidence and mortality rates, is a major health problem around the world. Also, the type II diabetes is a type of metabolic disorder characterized by increased blood glucose, which is due to insulin resistance, insulin deficiency, or both. The current study aimed to assess the mean platelet volume (MPV) in type 2 diabetes patients compared to nondiabetics, and determine the correlation between MPV and fasting blood glucose, glycosylated hemoglobin (HbA1c). Methods: This case-control study was conducted on all patients (n = 120) diagnosed with diabetes referred to the clinical laboratory of Bechr('39')sat Hospital in Hamadan City, Iran, during 2015-2016. The patients were divided into the two groups of case and control (n = 60, each group). The mean platelet volume was measured by an automated blood cell counter. The blood glucose and HbA1c levels were also measured in both groups. Data were analyzed using the Chi-square, t test and Mann-Whitney tests with the SPSS software version 16. The significance level was equal to 0.05. Results: The mean age of the control group was 41.78 years and that of the case group was 41.58 years. The mean platelet volume was 8.42% in the case group and 7.74% in the control group, which showed a significant difference between the two groups (P = 0.001). The mean platelet volume in people with HbA1c less than 7 in the case group was less than those who had HbA1c more than 7 and this difference was statistically significant (P = 0.001). Conclusion: The mean platelet volume in diabetic patients was significantly higher than in the nondiabetic group. So, it seems that the elevated MPV can be used as a parameter for the diagnosis of vascular complications of diabetes.

Abstract Background Arachidonic acid metabolism by cyclooxygenase (COX) is a major pathway for blood platelets’ activation, which is associated with pro-thrombotic platelet activity and the production of pro-inflammatory mediators. Inhibition of COX activity is one of the major means of anti-platelet pharmacotherapy preventing arterial thrombosis and reducing the incidence of cardiovascular events. Recent studies have presented that a silymarin (standardized extract of Milk thistle (Silybum marianum)) can inhibit the COX pathway. Accordingly, the aim of our study was to determine the effects of three major flavonolignans (silybin, silychristin and silydianin) on COX pathway activity in blood platelets. Methods We determined the effect of flavonolignans on arachidonic acid induced blood platelet aggregation, COX pathway metabolites formation, as well as COX activity in platelets. Additionally, we analysed the potential mechanism of this interaction using the bioinformatic ligand docking method. Results We observed that tested compounds decrease the platelet aggregation level, both thromboxane A2 and malondialdehyde formation, as well as inhibit the COX activity. The strongest effect was observed for silychristin and silybin. In our in silico study we showed that silychristin and silybin have conformations which interact with the active COX site as competitive inhibitors, blocking the possibility of substrate binding. Conclusions The results obtained from this study clearly present the potential of flavonolignans as novel antiplatelet and anti-inflammatory agents.

The aim of the study was to determine the morphological changes in the cellular elements of blood in rats of different ages under conditions of prolonged hypokinesia. Research into the structural and functional properties of platelets and erythrocytes was carried out by electron microscope and by biochemical methods in 90 mature male rats aged 2, 12 and 24 months. We found that in young (2 month animals) there was a significant increase in the relative content of activated platelets while the normal content of aggregated and degranulated forms with the appearance of single platelets was maintained with an imbalance of alpha and delta granules. In 12-month-old animals, platelet hemostasis disorders were manifested by a significant increase in the relative content of activated platelets (by 125.8–134.7%) with an increase in aggregated and degranulated forms, the appearance of numerous platelets with an imbalance of alpha- and delta-granules, and reduction of mitochondria (by 24.9–27.8%). In 24 month old animals there was a sharp violation of platelet hemostasis due to a significant increase in the content of activated, degranulated and aggregated platelets, the release of the majority of granules, the development of intravascular platelet hyperactivation, an increase in the number of reversible and irreversibly transformed erythrocytes, an increase in the level of aggregation, in particular the appearance of complex cellular aggregates and bizarre forms of red blood cells. The greatest degree of manifestation of morpho-functional changes was revealed in animals aged 24 months, with relative stability of the hemostasis system in 2 and 12 month old animals. Our results showed that irrespective of age, the degree of disturbance of platelet-erythrocyte hemostasis rose as the period of hypokinesia increased and also depended on the increase in the level of serum creatinine. Taken together, intravascular platelet hyperactivation, an imbalance in the content of all types of granules, the transformation of surface cytoarchitectonics of erythrocytes, and the formation of platelet aggregates may play the role of an early predictor of the development of hypokinetic disease

In the present study, the age‐ and sex‐related differences in platelet ultrastructure were investigated using transmission electron microscopy (TEM). A total of 15 healthy volunteers were grouped according to age, with 5 people in each of the following groups: young group (25‐45 years), middle‐aged group (46‐65 years), and old‐aged group (> 65 years). In the TEM micrographs, the internal components, specifically the α‐granules, dense granules, and lysosomal granules, of 20 platelets were counted for each group. Two‐way analysis of variance of age and sex variance was used to compare the results. The ultrastructure of the platelets in the old‐aged group was observed to be quite different from those of the young and middle‐aged groups. Specifically, with ageing, the platelet membrane becomes more irregular in shape and non‐smooth, and multiple platelet membrane ruptures are observed. Furthermore, the pseudopodia and protuberances become more numerous and slender, and the number of α‐granules is significantly reduced. These morphological changes indicate that ageing may affect the function of platelets, which in turn affects the efficacy of platelet concentrates. Thus, the effects of age should be considered when using platelet concentrates prepared from elderly autologous blood. [ABSTRACT FROM AUTHOR]

Spent hop extract (SHE) is hypothesized to possess multifaceted anticoagulant effect and to reduce platelet reactivity in a direct manner and to improve the antiplatelet action of endothelium. The results demonstrated that SHE, rich in flavanols (50% of total phenolic compounds), hydroxycinnamic acids, proanthocyanidin oligomers, flavan-3-ol monomers, and flavonol glycosides, inhibited ADP-induced platelet aggregation up to 11% for 7.5 µg/ml or up to 23% for 15 µg/ml, P

Traditionally, platelets are known to play an important role in haemostasis and thrombosis; however, they serve also as important modulators of inflammation and immunity. Platelets secrete adhesion molecules and cytokines, interact with leukocytes and endothelium, and express toll-like receptors involved in a direct interaction with pathogens. Platelets express A 2A and A 2B subtypes of receptors for adenosine. The activation of these receptors leads to an increase in cAMP concentration in the cytoplasm, thereby resulting in inhibited secretion of pro-inflammatory mediators and reduced cell activation. Therefore, platelet adenosine receptors could be a potential target for inhibiting platelet activation and thus down-regulating inflammation or immunity. The biological effects of adenosine are short-lasting, because the compound is rapidly metabolized; hence, its lability has triggered efforts to synthesize new, longer-lasting adenosine analogues. In this article, we have reviewed the literature regarding the pharmacological potential of adenosine and other agonists of A 2A and A 2B receptors to affect platelet function during inflammation. LINKED ARTICLES: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc., (© 2023 British Pharmacological Society.)

Diagnostic value of blood platelet (PLT) and serum total bilirubin (TBIL) for central serous chorioretinopathy (CSC) was investigated. A total of 537 patients with CSC and 182 people with normal physical conditions were selected from June 2012 to August 2016. The 537 patients included 294 males and 243 females with an average age of 45.5±17.8 years, and all patients were treated in the Department of Ophthalmology of Yantai Hospital of Traditional Chinese Medicine and the Department of Ophthalmology of Yantai Liuhuangding Hospital. Clinical data of the patients were retrospectively analyzed. The 182 people with normal physical conditions included 103 males and 79 females with an average age of 43.6±15.2 years, and they were set as the control group. PLT and TBIL tests at admission and after treatment were collected and compared between CSC and the control group to analyze the diagnostic values of PLT and TBIL for CSC. PLT level in the CSC group was significantly higher than that in the control group, but TBIL level in the CSC group was significantly lower than that in the control group (p<0.05). Linear correlation analysis showed that PLT was a risk factor for CSC, and TBIL was a protective factor for CSC. The sensitivity of PLT and TBIL in diagnosis of CSC was 75.2 and 72.7%, respectively, and the specificity of PLT and TBIL in diagnosis of CSC was 65.8 and 63.3%, respectively. PLT of CSC patients was significantly higher than that of the control group, and TBIL of CSC patients was significantly lower than that of the control group, but they both gradually reduced to normal levels after treatment, which can be regarded as the index for the clinical diagnosis of CSC in the future. [ABSTRACT FROM AUTHOR]

Background: Arachidonic acid metabolism by cyclooxygenase (COX) is a major pathway for blood platelets' activation, which is associated with pro-thrombotic platelet activity and the production of pro-inflammatory mediators. Inhibition of COX activity is one of the major means of anti-platelet pharmacotherapy preventing arterial thrombosis and reducing the incidence of cardiovascular events. Recent studies have presented that a silymarin (standardized extract of Milk thistle (Silybum marianum)) can inhibit the COX pathway. Accordingly, the aim of our study was to determine the effects of three major flavonolignans (silybin, silychristin and silydianin) on COX pathway activity in blood platelets. Methods: We determined the effect of flavonolignans on arachidonic acid induced blood platelet aggregation, COX pathway metabolites formation, as well as COX activity in platelets. Additionally, we analysed the potential mechanism of this interaction using the bioinformatic ligand docking method. Results: We observed that tested compounds decrease the platelet aggregation level, both thromboxane A2 and malondialdehyde formation, as well as inhibit the COX activity. The strongest effect was observed for silychristin and silybin. In our in silico study we showed that silychristin and silybin have conformations which interact with the active COX site as competitive inhibitors, blocking the possibility of substrate binding. Conclusions: The results obtained from this study clearly present the potential of flavonolignans as novel antiplatelet and anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

The fast bloodstream of animals is associated with large shear stresses. To withstand these conditions, blood cells have evolved a special morphology and a specific internal architecture to maintain their integrity over several weeks. For instance, nonmammalian red blood cells, mammalian erythroblasts, and platelets have a peripheral ring of microtubules, called the marginal band, that flattens the overall cell morphology by pushing on the cell cortex. In this work, we model how the shape of these cells stems from the balance between marginal band rigidity and cortical tension. We predict that the diameter of the cell scales with the total microtubule polymer and verify the predicted law across a wide range of species. Our analysis also shows that the combination of the marginal band rigidity and cortical tension increases the ability of the cell to withstand forces without deformation. Finally, we model the marginal band coiling that occurs during the diskto- sphere transition observed, for instance, at the onset of blood platelet activation. We show that when cortical tension increases faster than cross-linkers can unbind, the marginal band will coil, whereas if the tension increases more slowly, the marginal band may shorten as microtubules slide relative to each other. [ABSTRACT FROM AUTHOR]

Megakaryocytes are commonly known as large, polyploid, bone marrow resident cells that contribute to hemostasis through the production of platelets. Soon after their discovery in the 19th century, megakaryocytes were described in tissue locations other than the bone marrow, specifically in the lungs and the blood circulation. However, the localization of megakaryocytes in the lungs and the contribution of lung megakaryocytes to the general platelet pool has only recently been appreciated. Moreover, the conception of megakaryocytes as uniform cells with the sole purpose of platelet production has been challenged. Here, we review the literature on megakaryocyte cell identity and location with a special focus on recent observations of megakaryocyte subpopulations identified by transcriptomic analyses., Competing Interests: Disclosures None.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by immune-mediated destruction of platelets, resulting in a decreased blood platelet count (less than 100 x 10 9 /L) in the absence of other known etiology of thrombocytopenia. ITP is uncommon in adult males. The signs and symptoms of ITP vary widely and are quite diverse. The degree of thrombocytopenia and bleeding are not always correlated. Timely diagnosis, intervention, and regular monitoring can easily prevent complications. We report a case of a 22-year-old male presented with gum bleeding along with purpura and ecchymosis over the upper limb, lower limb, trunk, and face., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Thapa Chhetri et al.)

Background--Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. Methods and Results--We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With Drug- Eluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively (P<0.001). Associations between HPR and adverse events were uniform across CKD strata without evidence of interaction. Conclusions--HPR is more common among those with versus without CKD, an association that is attributable to confounding risk factors that are more prevalent in CKD. The impact of HPR on ischemic and bleeding events is similar irrespective of CKD status. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effects of Riboflavin (RB) combined with different doses of UV on Platelet Concentrate (PC) which was infected by three models of virus. Platelet quality after treatment was also assessed. Methods: Three models of virus used in this study were Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV), and Polio virus, which were added to PC. After photochemical treatment with RB and UV light, residual viral infectivity was titrated using 50% Tissue Culture Infective Dose (TCID50)/ml. This treatment was done with concentration of 50 μM of RB and different doses of UV light (0.24, 0.48, 0.97, 1.29 J/cm2). Platelet quality was assessed by measuring pH, Lactate Dehydrogenase (LDH), MTT assay and cell count after treatments and during 4 days of storage against control groups. Results: Concentration of 50 μMRB with combination of 1.29 J/cm2 dose of UV resulted in the highest titer reduction of VSV (4 log10) and HSV (4.26 log10) and lowest titer reduction of Polio virus (2.6 log10). No significant difference was observed between different doses in comparison with control groups. In all treatment groups, the storage stability of platelets in PC was in the acceptable range in comparison with control group. Conclusion: This study indicated that RB/UV treatment was a promising pathogen reduction technique in PC and had limited effects on platelet quality. However, further optimization of this method is necessary to deal with blood-borne viruses like non- enveloped viruses [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) is an odorless, colorless and non-irritating gas. Even a small amount of CO exposure is possibly associated with specific toxic effects. CO is also produced endogenously in the body as a byproduct of heme degradation catalyzed by heme oxygenase. More recently CO has been identified as a gasotransmitter in various biological systems. However, the biological role and the therapeutic potential of carbon monoxide is not clear. This review summarizes the negative and the positive functions of carbon monoxide in various biological systems, including cardiovascular system. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine" is presented.

BACKGROUND: Bleeding time (BT) is the oldest and simplest test for assessing the platelets (Plts) function. BT can affect by several factors such as race and diet, which has a wide reference range. The aim of this project is to determine the normal range of BT in Borujerd city. Determining the normal range of BT can help us to modify the definition of bleeding disorder and aspirin resistance. METHODS: This was cross-sectional study carried out in 2011-2012. Subjects with a history of coagulation disorders or a positive family history of coagulation disorders, consumption of anti-Plts, anti-histamines, and phenothiazine in the previous month and subject with Plt less than 150,000 were excluded. The samples were 505 volunteers who were referred from 16 urban and 9 rural clusters to research center. BT of the samples was determined according to Ivy simplate method considering national standard protocol in the selected persons. Normal range was calculated as mean ± 2 standard deviation. RESULTS: Of 505 volunteers, 50.4% were female. The range of BT was 2.8-2.95 min with mean of 2.79 ± 0.78 min. Range and mean of BT in women was 2.83-3.06 min and 2.88 ± 0.87 min, and range and mean of BT in men was 2.7-2.9 min and 2.69 ± 0.67 min; this difference was significant (P = 0.012). BT in urban and rural participants was 2.78 ± 0.79 and 2.77 ± 0.73 min. There was no significant difference between BT in urban and rural participants. CONCLUSION: The normal range of BT in Boroujerd was in the lower limit of the normal universal range. In this study, BT was significantly different in both genders, but its correlation with age, blood group, and place of residency was not significant. [ABSTRACT FROM AUTHOR]

Blood platelets are considered to be a peripheral marker in schizophrenia and other psychiatric disorders. Oxidative stress in schizophrenia may be responsible for changes in platelet metabolism and function; therefore, the aim of this study was to examine and compare the generation of superoxide anions and activity of an antioxidant enzyme (glutathione peroxidase [GPx]) in blood platelets in patients with schizophrenia and healthy subjects. The level of superoxide anions generated in platelets after thrombin and platelet-activating factor stimulation and activity of GPx in patients with schizophrenia and healthy volunteers was estimated. The results obtained from the study indicate that the generation of superoxide anions in platelets as a response of platelets in patients with schizophrenia to such activating factors as thrombin or platelet-activating factor is higher than in the response of platelets of healthy subjects. In platelets from schizophrenic patients, suppressed GPx activity of about 67% was observed. [ABSTRACT FROM AUTHOR]