Platelet Activation Research Articles

Platelet Metrics In Type 2 Diabetes: A Practical Tool For Assessing Vascular Complications

Background: Chronic metabolic disorder Type 2 Diabetes Mellitus (T2DM) is characterized by hyperglycemia, which is associated with a range of complications, particularly vascular complications that significantly contribute to morbidity and mortality among patients. The ability to predict these complications early is crucial for preventive strategies and patient management. This study provides an overview of the practicality of platelet parameters for predicting vascular complications in type 2 diabetes patients, highlighting their importance in diabetes management and the potential benefits of incorporating them into clinical practice as accessible and cost-effective biomarkers for early risk assessment and improved patient management in the context of a global health challenge. Method: The study included 250 T2DM patients and 125 non-diabetic individuals. Participants were selected using convenience sampling from outpatient and inpatient departments. The diabetic group was further categorized based on the presence or absence of vascular complications. Laboratory analyses were conducted to determine HbA1C levels and platelet parameters. Data were analyzed using SPSS version 21.0, applying non-parametric methods to evaluate platelet indices, HbA1c levels, and demographic variables. Result: Elevated HbA1c, platelet count, MPV (Mean Platelet Volume), and PDW (Platelet Distribution Width) values were observed in T2DM patients with vascular complications, distinguishing them from T2DM patients without such complications and healthy subjects. The patient with Diabetes Mellitus and vascular complications exhibited an MPV of 14.44 fL, PDW of 19.21%, and a platelet count of 488.8 x 10^3/µL. These values surpass the normal ranges, suggesting heightened platelet activity, size variability, and a prothrombotic state. Conclusion: The integration of MPV and PDW platelet indices could be an economical approach to T2DM vascular risk management, potentially bettering healthcare in rural settings.

Pathological roles of NETs-platelet synergy in thrombotic diseases: From molecular mechanisms to therapeutic targeting.

Pathological roles of NETs-platelet synergy in thrombotic diseases: From molecular mechanisms to therapeutic targeting.

SARS-CoV-2 S1 protein induces IgG-mediated platelet activation and is prevented by 1.8-cineole.

SARS-CoV-2 S1 protein induces IgG-mediated platelet activation and is prevented by 1.8-cineole.

Formononetin attenuates myocardial ischemia/reperfusion injury by regulating neutrophil extracellular traps formation and platelet activation via platelet CD36.

Formononetin attenuates myocardial ischemia/reperfusion injury by regulating neutrophil extracellular traps formation and platelet activation via platelet CD36.

FKBP5 inhibitor suppresses platelet activation and thrombosis by inhibiting IKBKE/PI3K/Rap1 pathway.

FKBP5 inhibitor suppresses platelet activation and thrombosis by inhibiting IKBKE/PI3K/Rap1 pathway.

Low functional capacity in peripheral artery disease is associated with increased platelet activity and cardiovascular events.

Low functional capacity in peripheral artery disease is associated with increased platelet activity and cardiovascular events.

2-Methoxybenzoic acid ameliorates arterial thrombosis via inhibiting carbon anhydrase activity in platelet.

2-Methoxybenzoic acid ameliorates arterial thrombosis via inhibiting carbon anhydrase activity in platelet.

A parametric study of motion and attachment to capillary walls of circulating tumor cells (CTCs) interacting with non-activated and activated platelets.

A parametric study of motion and attachment to capillary walls of circulating tumor cells (CTCs) interacting with non-activated and activated platelets.

Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study.

Prolonged fasting (PF), defined as abstaining from energy intake for ≥4 consecutive days, has gained interest as a potential health intervention. However, the biological effects of PF on the plasma proteome are not well understood. In this study, we investigated the effects of a medically supervised water-only fast (mean duration: 9.8 ± 3.1 days), followed by 5.3 ± 2.4 days of guided refeeding, in 20 middle-aged volunteers (mean age: 52.2 ± 11.8 years; BMI: 28.8 ± 6.4 kg/m2). Fasting resulted in a 7.7% mean weight loss and significant increases in serum beta-hydroxybutyrate (BHB), confirming adherence. Untargeted high-dimensional plasma proteomics (SOMAScan, 1,317 proteins) revealed multiple adaptations to PF, including preservation of skeletal muscle and bone, enhanced lysosomal biogenesis, increased lipid metabolism via PPARα signaling, and reduced amyloid fiber formation. Notably, PF significantly reduced circulating amyloid beta proteins Aβ40 and Aβ42, key components of brain amyloid plaques. In addition, PF induced an acute inflammatory response, characterized by elevated plasma C-reactive protein (CRP), hepcidin, midkine, and interleukin 8 (IL-8), among others. A retrospective cohort analysis of 1,422 individuals undergoing modified fasting confirmed increased CRP levels (from 2.8 ± 0.1 to 4.3 ± 0.2 mg/L). The acute phase response, associated with transforming growth factor (TGF)-β signaling, was accompanied by increased platelet degranulation and upregulation of the complement and coagulation cascade, validated by ELISAs in blood and urine. While the acute inflammatory response during PF may serve as a transient adaptive mechanism, it raises concerns regarding potential cardiometabolic effects that could persist after refeeding. Further investigation is warranted to elucidate the long-term molecular and clinical implications of PF across diverse populations.

Maternal platelet-derived factors induce trophoblastic LAIR2 expression to promote trophoblast invasion and inhibit platelet activation at the fetal-maternal interface.

During human placentation, extravillous trophoblasts (EVTs) arising from cell column trophoblasts (CCTs) invade the highly differentiated uterine mucosa, called decidua, where they erode blood vessels and replace vascular endothelial cells. Maternal platelets have been detected in intercellular gaps of CCTs, but their physiological role remains unclear. This study aimed to elucidate the impact of platelet-derived factors on trophoblasts that are exposed to maternal platelets through erosion of decidual blood vessels. Trophoblast cell line ACH-3P spheroids were incubated either with platelet-derived factors or isolated platelets obtained from pregnant women and then subjected to RNA sequencing followed by validation using quantitative polymerase chain reaction, ELISA, and in situ padlock hybridization. Among the deregulated genes, leukocyte associated immunoglobulin-like receptor 2 (LAIR2) expression was confirmed in first trimester placenta and primary trophoblast organoids. The functional role of LAIR2 in trophoblast invasion and platelet activation was studied. Platelet-derived factors altered the transcriptional profile of ACH-3P spheroids, including deregulation of genes linked to embryonic development. Among them, LAIR2 was exclusively detected in CCTs and invaded EVTs of first trimester decidua. Histology showed extravasated maternal erythrocytes within interstitial gaps of highly invaded decidua samples, coinciding with LAIR2-positive EVTs. LAIR2 inhibited type 1 collagen-induced platelet activation and enhanced invasiveness of trophoblasts. This study suggests that maternal platelet-derived factors affect the transcriptional profile of trophoblasts, including upregulation of LAIR2, which may be involved in fine-tuning the coagulation of maternal blood leaking from eroded decidual blood vessels and could increase the invasiveness of EVTs into the decidua through an autocrine mechanism.

Long term stability of preservative-free and lyophilized PRGF eye drops stored at different temperature conditions: in vitro comparative study.

Long term stability of preservative-free and lyophilized PRGF eye drops stored at different temperature conditions: in vitro comparative study.

Refractory delayed-onset heparin induced thrombocytopenia (HIT) without thrombosis, treated with intravenous immunoglobulin.

Refractory delayed-onset heparin induced thrombocytopenia (HIT) without thrombosis, treated with intravenous immunoglobulin.

Thrombotic response to mechanical circulatory support devices.

Thrombotic response to mechanical circulatory support devices.

Disulfide bond control of platelet αIIbβ3 integrin.

Disulfide bond control of platelet αIIbβ3 integrin.

Chondroitin sulfate and Cys-Ala-Gly peptides coated ZE21B magnesium alloy for enhanced corrosion resistance and vascular compatibility.

Chondroitin sulfate and Cys-Ala-Gly peptides coated ZE21B magnesium alloy for enhanced corrosion resistance and vascular compatibility.

Fc-engineered anti-CD9 antibodies with reducing platelet toxicity and efficacy against acute lymphoblastic leukemia.

e14501 Background: While CD19/CD22-targeted immunotherapies have advanced, treatment outcomes for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) remain unsatisfactory. CD9 is emerging as a key therapeutic and prognostic target in ALL, but severe platelet toxicity caused by CD9 antibodies has hampered clinical applications. This study focuses on engineering a safe and effective CD9-based therapeutic antibody to address these challenges. Methods: Humanized CD9 antibodies were analyzed for their specificity and binding affinity to the CD9 antigen and ALL cell lines. Efficacy was assessed in both cell line-derived and patient-derived xenograft (PDX) models. Platelet toxicity was evaluated through CD62P expression, platelet aggregation assays, and studies in FcγRIIA transgenic mice. Mechanistic investigations included assays for cell proliferation, apoptosis, imaging, and antibody-dependent cellular cytotoxicity (ADCC). Results: Two murine monoclonal antibodies (mAbs) exhibited distinct binding properties, which were preserved after humanization (hAbs). Both mAbs and hAbs significantly delayed leukemia progression in NOD/SCID mice engrafted with the 697 cell line, leading to improved survival. IgG-based hAbs activated platelets, whereas Fab or scFv fragments did not, indicating Fc domain involvement. Introducing the N297A mutation into the Fc domain prevented platelet activation and aggregation, as confirmed by the lack of CD62P expression and optical aggregation. No thrombocytopenia was observed in FcγRIIA transgenic mice. In PDX models of ALL relapsed from CD19-targeted therapies, N297A-modified hAbs reduced leukemia burden by over 98%. Fc-engineered hAbs triggered homotypic aggregation, leading to direct cell death and growth inhibition in CD9+ ALL cells, independent of ADCC. Conclusions: Engineering the Fc domain of CD9 antibodies mitigates platelet toxicity without compromising therapeutic efficacy in refractory ALL, providing a promising avenue for clinical translation. Further studies in large animal models are ongoing.

Effects of low-dose rivaroxaban combined with low-dose aspirin versus low-dose aspirin alone on in vivo platelet activation, endothelial function and inflammation in type 2 diabetes patients with stable atherosclerotic disease: the RivAsa randomized, crossover study.

Effects of low-dose rivaroxaban combined with low-dose aspirin versus low-dose aspirin alone on in vivo platelet activation, endothelial function and inflammation in type 2 diabetes patients with stable atherosclerotic disease: the RivAsa randomized, crossover study.

Aspirin Plus Clopidogrel Reduces Infection Risk Compared With Aspirin or Clopidogrel Alone in Acute Ischemic Stroke.

Aspirin Plus Clopidogrel Reduces Infection Risk Compared With Aspirin or Clopidogrel Alone in Acute Ischemic Stroke.

The Role of Microplastics in Elevated Risk and Tissues Metabolic Alterations in Uterine Fibroid of Female Patients.

The Role of Microplastics in Elevated Risk and Tissues Metabolic Alterations in Uterine Fibroid of Female Patients.

<i>Ex vivo</i> observation of the thromboinflammation process in patients with chronic heart failure

BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide. Chronic heart failure is accompanied by hemodynamic disturbances, including alterations in blood microrheological properties. Changes in erythrocyte deformability may lead to impaired activation and interaction of platelets and neutrophils, contributing to thrombosis and the progression of chronic heart failure. AIM: Determination of neutrophil activity and thrombus formation in an ex vivo model of thromboinflammation in patients with chronic heart failure with simultaneous assessment of blood microrheology. METHODS: The study involved 21 patients with a diagnosis of chronic heart failure and 8 healthy volunteers. The patients and volunteers underwent determination of the biochemical composition of blood plasma and assessment of the condition of the blood elements. The thromboinflammation was evaluated in whole heparinized blood using parallel-flat flow chambers coated with type I collagen at a shear rate of 100 1/s. The deformability parameters of erythrocytes were measured in vitro using the method of laser diffractometry. Erythrocyte aggregation was determined by diffuse light scattering from whole blood samples. RESULTS: For thrombus areas, no statistical differences were found between healthy controls and patients with chronic heart failure. However, the neutrophil velocities for patients with chronic heart failure were significantly lower than for healthy controls (0.11 ± 0.02 µm/s for chronic heart failure versus 0.16 ± 0.04 µm/s for healthy controls). The thrombus areas for patients with chronic heart failure at 5 and 10 minutes of growth correlated with the concentration of red blood cells and the average volume of red blood cells. Also, the aggregation coefficients of erythrocytes A1 and A2 characterizing the intensity of the process of formation of linear and three-dimensional aggregates positively correlated with thrombus area. In addition, mean corpuscular volume, erythrocyte deformability indices, and yield strength of the erythrocytes correlated with neutrophil movement velocities. CONCLUSION: Thus, although there is no significant change in thrombus formation in chronic heart failure, however, we can talk about a decrease in neutrophil activity, possibly associated with the increase in blood viscosity.