Platelet integrin αIIbß3 plays a key role in a venous thrombogenesis mouse model.

Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. VT is initiated by the accumulation of platelets and neutrophils at sites of endothelial cell activation. A role for platelet αIIbß3 in VT is not established, a task complicated by the increased bleeding risk caused by partial agonists such as tirofiban. Here, we show that m-tirofiban, a modified version of tirofiban, does not agonize αIIbß3 based on lack of neoepitope expression and the cryo-EM structure of m-tirofiban/full-length αIIbß3 complex. m-tirofiban abolishes agonist-induced platelet aggregation while preserving clot retraction ex vivo and, unlike tirofiban, it suppresses venous thrombogenesis in a mouse model without increasing bleeding. These findings establish a key role for αIIbß3 in VT initiation and suggest that m-tirofiban and compounds with a similar structurally-defined mechanism of action merit consideration as potential thromboprophylaxis agents in patients at high risk for VT and hemorrhage.

The potential of platelet to high-density lipoprotein cholesterol ratio (PHR) as a novel biomarker for heart failure.

Heart failure (HF) is closely linked to platelet counts and lipid levels. The platelet-to-high-density lipoprotein cholesterol ratio (PHR) is a novel marker for assessing cardiovascular disease. This study investigates the relationship between PHR and HF. We analyzed data from ten consecutive NHANES survey cycles (1998-2018), focusing on self-reported HF diagnoses with complete PHR information. PHR was calculated as platelet count divided by HDL-C (mmol/L). A multivariate logistic regression model was used to examine the association between PHR and HF, with subgroup analyses to identify potential influencing factors. RCS curve plotting and threshold effect analysis were employed to describe non-linear relationships. The study included 31,410 adults aged 20-85 years. The multivariate logistic regression indicated that individuals with the highest PHR had 82% increased likelihood of HF compared to those with the lowest PHR (OR = 1.82; 95% CI, 1.37-2.40, P < 0.001). Subgroup analyses revealed no significant interactions between PHR and specific subgroups (P > 0.05), except in those with alcohol consumption (yes/no) and BMI subgroups (P < 0.05). The association between PHR and HF was non-linear, with a notable turning point at 281.53. Elevated PHR is significantly associated with HF, suggesting it may serve as an effective clinical indicator for monitoring HF risk. Larger prospective cohort studies are needed to validate these findings and further assess the clinical utility of PHR in cardiovascular risk assessment.

Platelet activation near point-like source of agonist: Experimental insights and computational model.

Disorders of hemostasis resulting in bleeding or thrombosis are leading cause of mortality in the world. Blood platelets are main players in hemostasis, providing the primary response to the vessel wall injury. In this case, they rapidly switch to the activated state in reaction to the exposed chemical substances such as ADP, collagen and thrombin. Molecular mechanisms of platelet activation are known, and detailed computational models are available. However, they are too complicated for large-scale problems (e.g. simulation of the thrombus growth) where less detailed models are required, which still should take into account the variation of agonist concentration and heterogeneity of platelets. In this paper, we present a simple model of the platelet population response to a spatially inhomogeneous stimulus. First, computational nodes modeling platelets are placed randomly in space. Each platelet is assigned the specific threshold for agonist, which determines whether it becomes activated at a given time. The distribution of the threshold value in a population is assumed to be log-normal. The model was validated against experimental data in a specially designed system, where the photorelease of ADP was caused by localized laser stimulus. In this system, a concentration of ADP obeys 2-dimensional Gaussian distribution which broadens due to the diffusion. The response of platelets to the point-like source of ADP is successfully described by the presented model. Our results advance the understanding of platelet function during hemostatic response. The simulation approach can be incorporated into larger computational models of thrombus formation.

Cell-bound complement activation products in antiphospholipid antibody-positive patients without other systemic autoimmune rheumatic diseases.

The objective of this study was to analyze complement activation in antiphospholipid antibody (aPL)-positive patients without other systemic autoimmune rheumatic diseases, using C3/C4 and cell-bound complement activation products (CB-CAPs) (B-lymphocytes [BC4d], erythrocytes [EC4d], and platelets [PC4d]). Persistently aPL-positive patients with or without aPL-related clinical manifestations (thrombotic APS [TAPS], microvascular APS [MAPS], obstetric APS, thrombocytopenia [TP], and/or hemolytic anemia [HA]) were enrolled in a single center study. Blood and clinical data were collected at baseline; a subgroup of patients completed 6- or 12-month follow-up. At baseline, 4/31 (13%) patients had decreased C3/C4, while 7/29 (24%) had elevated BC4d, 11/33 (33%) EC4d, and 12/32 (38%) PC4d. Based on different aPL profiles, all patients with decreased C3/C4 or elevated BC4d, EC4d, and PC4d had triple aPL or isolated lupus anticoagulant positivity. Based on different aPL clinical phenotypes, the number of patients with strongly positive EC4d and PC4d were proportionally higher in those with MAPS/TP/HA, compared to TAPS or no APS. Compared to baseline, the frequencies of BC4d, EC4d, and PC4d positivity were not significantly different in the subgroup of patients during their 6- or 12-month follow-up. There was a weak correlation between C3/C4 and CB-CAPs, especially for PC4d. In summary, complement activation in aPL-positive patients varies based on aPL profiles and clinical phenotypes. Given the higher percentage of aPL-positive patients with abnormal CB-CAPs, compared to C3/C4, and the poor inverse correlation between CB-CAPs and C3/C4, our study generates the hypothesis that CB-CAPs have a role in assessing disease activity and thrombosis risk in aPL-positive patients.

Can maternal inflammatory and nutritional status, evaluated by the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI) in the first trimester, predict late-onset fetal growth restriction?

OBJECTIVE: The aim of this study was to evaluate the potential of immunonutritional markers, specifically the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI), in predicting late-onset fetal growth restriction (LO-FGR) during the first trimester. MATERIALS AND METHODS: This retrospective study was conducted at a tertiary care center between October 2022 and August 2023. The study included a total of 213 singleton pregnancies, with 99 women in the LO-FGR group and 114 in the healthy control group, matched by maternal age and gestational age at delivery. All blood samples were collected between 11 and 14 weeks of gestation (during the first-trimester screening test). We analyzed first-trimester laboratory parameters, specifically focusing on hemoglobin levels, white blood cells (WBCs), lymphocytes, platelets, and albumin levels. Afterwards, we calculated the HALP score and PNI, and then compared the values of both groups. RESULTS: Both HALP score (3.58 ± 1.31 vs. 4.19 ± 1.8, p = 0.012) and PNI (36.75 ± 2.9 vs. 39.37 ± 3.96, p < 0.001) were significantly lower in the FGR group than in the control group. The HALP score cut-off value of < 3.43 in predicting FGR had a sensitivity of 62.3% and specificity of 54.5% (AUC = 0.600, 95% CI: 0.528-0.672, p = 0.012). The PNI cut-off value of < 37.9 in predicting FGR had a sensitivity of 65.8% and specificity of 62.9% (AUC = 0.707, 95% CI: 0.632-0.778, p < 0.001). While the HALP score was not a significant predictor of composite adverse neonatal outcomes in the FGR group, PNI showed a cut-off value of < 37.7 with a sensitivity of 60.9% and specificity of 59.7% (AUC = 0.657, 95% CI: 0.581-0.733, p < 0.001). CONCLUSION: The HALP score and PNI are valuable prognostic tools for predicting the risk of FGR in the first trimester. Low PNI values are also associated with composite adverse neonatal outcomes in pregnancies complicated by FGR.

Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson's disease models.

BACKGROUND: The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade platelet concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects of platelet-extracellular vesicles (PEVs). Their potential in managing neurodegenerative conditions like traumatic brain injury (TBI) and Parkinson's disease (PD) warrants further exploration. We aimed here to characterize the composition of a PEV preparation isolated from platelet concentrate (PC) supernatant, and determine its neuroprotective potential and neurorestorative effects in cellular and animal models of TBI and PD. METHODS: We isolated PEVs from the supernatant of clinical-grade PC collected from healthy blood donors utilizing high-speed centrifugation. PEVs were characterized by biophysical, biochemical, microscopic, and LC-MS/MS proteomics methods to unveil biological functions. Their functionality was assessed in vitro using SH-SY5Y neuronal cells, LUHMES dopaminergic neurons, and BV-2 microglial cells, and in vivo by intranasal administration in a controlled cortical impact (CCI)-TBI model using 8-weeks-old male C57/BL6 mice, and in a PD model induced by MPTP in 5-month-old male C57/BL6 mice. RESULTS: PEVs varied in size from 50 to 350 nm, predominantly around 200 nm, with concentrations ranging between 1010 and 1011/mL. They expressed specific platelet membrane markers, exhibited a lipid bilayer by cryo-electron microscopy and, importantly, showed low expression of pro-coagulant phosphatidylserine. LC-MS/MS indicated a rich composition of trophic factors, including neurotrophins, anti-inflammatory agents, neurotransmitters, and antioxidants, unveiling their multifaceted biological functions. PEVs aided in the restoration of neuronal functions in SH-SY5Y cells and demonstrated remarkable neuroprotective capabilities against erastin-induced ferroptosis in dopaminergic neurons. In microglial cells, they promoted anti-inflammatory responses, particularly under inflammatory conditions. In vivo, intranasally delivered PEVs showed strong anti-inflammatory effects in a TBI mouse model and conserved tyrosine hydroxylase expression of dopaminergic neurons of the substantia nigra in a PD model, leading to improved motor function. CONCLUSIONS: The potential of PEV-based therapies in neuroprotection opens new therapeutic avenues for neurodegenerative disorders. The study advocates for clinical trials to establish the efficacy of PEV-based biotherapies in neuroregenerative medicine.

Effect of Topical Human Platelet Extract (HPE) for Facial Skin Rejuvenation: A Histological Study of Collagen and Elastin.

BACKGROUND: Regenerative aesthetics has garnered significant attention. In this toolkit, exosomes are small extracellular vesicles derived from various sources such as platelets. OBJECTIVE: To characterize the cosmetic effect and tolerability of topical human platelet-derived extract (HPE), Intense Serum (Rion Aesthetics, Inc., Rochester, MN), on facial skin rejuvenation after 12 weeks of twice daily use without any confounding aesthetic procedures. MATERIALS AND METHODS: This prospective, single-arm, non-randomized, evaluator-blinded clinical study evaluated subjects at baseline and 12 weeks using participant questionnaires and photo-documentation with Canfield VISIA-CR 3D PRIMOS. The histological evaluation included Masson's Trichrome for collagen and Verhoeff-Van Gieson staining for elastin. Electron microscopy characterized collagen bundle thickness. RESULTS: Fifty-six participants (mean age: 54 years old) were enrolled. Following topical HPE use, 87.3% of subjects reported improvement in facial skin aging including sustained pigment reduction and improvement in luminosity and color evenness at 12 weeks (P≤0.001). Histology revealed a significant increase in collagen fibril thickness at 12 weeks (P≤0.0001). No serious adverse effects. CONCLUSION: This study demonstrates improvement in facial skin health after topical HPE use, supported by collagen and elastin formation in the dermis. The product is well-tolerated, and participants were satisfied with the overall cosmetic outcome. J Drugs Dermatol. 2024;23(9):735-740. doi:10.36849/JDD.8162.

The Relationship between Vitamin D, Inflammatory Markers, and Insulin Resistance in Children.

OBJECTIVE: In this study, we investigated 25-hydroxyvitamin D (25(OH)D, vitamin D), inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte/HDL-C ratio (MHR) and plasma atherogenic index (PAI) and possible relationships with insulin resistance (IR) in children. METHODS: A total of 210 individuals, including 96 children with IR and 114 children without IR, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. RESULT: Compared to patients without IR, NLR, PLR, SII, and MHR were significantly higher in patients with IR. Fasting insulin, PAI, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß were significantly higher and quantitative insulin sensitivity check index (QUICKI) was considerably lower in patients with IR compared to those without IR. NLR, SII, and MHR were lower in normal vitamin D groups than the others (p < 0.001). PLR was lower in the group with normal vitamin D levels than the groups with insufficient or deficient levels of vitamin D (D < 21). CONCLUSIONS: We found that vitamin D deficiency in childhood is related to increased levels of circulating inflammatory markers (NLR, PLR, MHR, PAI), IR, and decreased insulin sensitivity. According to our results, supplementation of vitamin D may be beneficial in averting IR and enhanced systemic inflammation.

[Platelet-specific Rictor knockout inhibits platelet production and activation and reduces thrombosis in mice].

OBJECTIVE: To investigate the effects of platelet-specific Rictor knockout on platelet activation and thrombus formation in mice. METHODS: PF4-Cre and Rictorfl/fl transgenic mice were crossed to obtain platelet-specific Rictor knockout (Rictor-KO) mice and wild-type mice (n=65), whose expression levels of Rictor, protein kinase B (AKT) and p-AKT were detected using Western blotting. Platelet counts of the mice were determined using routine blood tests, and hemostatic function was assessed by tail vein hemorrhage test. Venous thrombosis models were established in the mice to evaluate the effect of Rictor knockout on thrombosis. Platelet aggregation induced by ADP and thrombin was observed in Rictor-KO and wild-type mice, and flow cytometry was used to analyze the expression levels of integrin αIIbß3 and CD62P in resting and activated platelets. Plasma PF4 levels were determined with ELISA. Megakaryocytes from Rictor-KO and wild-type mice were incubated by vWF immunohistochemical antibody and APC-CD41 antibody to detect the number and ploidy of megakaryocytes, respectively. Platelet elongation on collagen surface was observed with scanning electron microscopy. RESULTS: Compared with the wild-type mice, Rictor-KO mice showed significantly decreased AKT phosphorylation, decreased platelet production, reduced thrombosis, and decreased platelet activation in response to ADP and thrombin stimulation. The Rictor-KO mice also showed lowered expression level of P-selectin protein and activation of integrin αIIbß3 with suppression of platelet extension, reduced plasma PF4 level and decreased number of megakaryocytes in the bone marrow. The ploidy of megakaryocytes and the mean area of proplatelets were both significantly decreased in Rictor-KO mice. CONCLUSION: Platelet-specific Rictor knockout inhibits platelet generation and activation to result in decreased thrombus formation in mice, suggesting the potential of mTORC2 activity inhibition as an efficient antithrombotic strategy.

Oxazolidinone antibiotics impair ex vivo megakaryocyte differentiation from hematopoietic progenitor cells and their maturation into platelets.

Oxazolidinones (linezolid and tedizolid) adverse reactions include thrombocytopenia, the mechanism of which is still largely unknown. In cultured cells, oxazolidinones impair mitochondrial protein synthesis and oxidative metabolism. As mitochondrial activity is essential for megakaryocyte differentiation and maturation into platelets, we examined whether oxazolidinones impair these processes ex vivo and alter, in parallel, the activity of mitochondrial cytochrome c-oxidase (CYTOX; enzyme partly encoded by the mitochondrial genome) and cell morphology. Human CD34+ cells were isolated, incubated with cytokines (up to 14 days) and clinically relevant oxazolidinone concentrations or in control conditions, and used for (i) clonogenic assays [counting of megakaryocyte (CFU-Mk), granulocyte-monocyte (CFU-GM), burst-forming unit-erythroid (BFU-E) colonies]; (ii) the measure of the expression of megakaryocyte surface antigens (CD34 to CD41 and CD42); (iii) counting of proplatelets; (iv) the measurement of CYTOX activity; and (v) cell morphology (optic and electron microscopy). Oxazolidinones caused a significant decrease in BFU-E but not CFU-Mk or CFU-GM colonies. Yet, the megakaryocytic lineage was markedly affected, with a decreased differentiation of CD34+ into CD41+/CD42+ cells, an abolition of proplatelet formation and striking decrease in the numbers of large polylobulated nucleus megakaryocytes, with a complete loss of intracellular demarcation membrane system, disappearance of mitochondria, and suppression of CYTOX activity. These alterations were more marked in cells incubated with tedizolid than linezolid. These data suggest that oxazolidinones may induce thrombocytopenia by impairing megakaryocytic differentiation through mitochondrial dysfunction. Pharmacological interventions to prevent this toxicity might therefore be difficult as mitochondrial toxicity is most probably inherently linked to their antibacterial activity.

Key role of activated platelets in the enhanced adhesion of circulating leucocyte-platelet aggregates to the dysfunctional endothelium in early-stage COPD.

Background: Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Methods: Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Results: Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Conclusion: Our data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.

Regulation of Platelet Activation and Coagulation: Current Concepts, Novel Targets, and Therapies.

Antiplatelet and anticoagulant therapies are cornerstones of secondary prevention in high-risk cardiovascular patients. Whereas in former days the focus was set on effective antithrombotic effects, more recent trials and guidelines placed emphasis on a more balanced approach, thus including the bleeding risk for an individualized therapy. Type, strength, combination, and duration are important components to modify the individual bleeding risk. Novel antiplatelet and anticoagulant agents have shown promising results that might offer safer options in the future for high-risk cardiovascular patients. This review aims to give an overview about established drug target and pharmacologic approaches that are currently in the pipeline.

[Effect of blue range light-emitting diode radiation on platelets and blood coagulation factors in patients with chronic ischemia of lower limbs]. / Vliyanie svetodiodnogo izlucheniya sinego diapazona na trombotsity i faktory svertyvaniya krovi u bol'nykh s khronicheskoi ishemiei nizhnikh konechnostei.

Chronic arterial insufficiency of lower limbs (CAILL) is a common cardiovascular disease that affects 200 million subjects worldwide: from 4 to 12% of people aged 55-70 years and 20% - over 70 years. The cause of blood circulation disorder in this disease is usually a complex of pathological changes including abnormality of vessel walls' anatomical structure or integrity, disorder of blood rheological properties and alterations of its thrombotic potential. Thus, the therapy of patients with CAILL aiming at hemostasis and, in particular, platelets' aggregation is one of the most urgent problems of medicine. OBJECTIVE: To study the effectiveness of blue range visible radiation combined with basic therapy to improve hemostasis in patients with CAILL. MATERIAL AND METHODS: The number of male patients with CAILL equal 63 aged 43-57 years was examined. Blood flow parameters on a fixed part of femoral artery outside the occlusion area were registered based on subjective criteria, number of painless steps and ultrasound doppler flowmetry according to the Fontaine-Pokrovsky classification. The second degree of ischemia was diagnosed in 38 patients, the third degree - in 25 patients. All patients received basic pharmacotherapy. Patients were divided into 2 groups by simple randomization method: control group included 18 patients with II degree of ischemia and 12 patients with III degree of ischemia who received basic pharmacotherapy combined with photohemotherapy (PHT). A set of commonly used laboratory methods for examination of blood coagulation system was applied to assess the effectiveness of PHT. The number of apparently healthy people equal 26 was examined to evaluate normal value of hemostasiological parameters. RESULTS: Basic pharmacological treatment had a certain positive effect on studied hemostasis parameters and its thrombotic component. However, they did not differ statistically significantly from similar parameters before treatment on the 14th day after treatment. As a result of comprehensive therapy the changes in hemostasis system had identical and statistically significant in percentage terms changes compared to norm and baseline in patients' subgroups of study group with II and III degrees of ischemia. In addition, most hemostasis parameters in patients with II degree of ischemia were close to those of apparently healthy volunteers. Hemostasis parameters in patients with III degree of ischemia decreased to the levels of patients with II degree of ischemia before treatment. CONCLUSION: The use of basic pharmacological therapy with optical exposure to blood by blue light allows to correct hemostasis and its thrombotic component in patients with CAILL.

[Developments of high-throughput sequencing-based diagnosis of congenital thrombocytopenia/platelet disorders in a registry study].

Congenital thrombocytopenia/platelet disorders are heterogeneous disorders of platelet number and/or function. Pathogenic variants in the genes implicated in megakaryocyte differentiation and platelet formation cause thrombocytopenia in these patients. Recent advances have elucidated several causative genes for these disorders, but identifying the underlying causative genes remains challenging. Patients with these disorders often receive inappropriate treatments, including glucocorticoids and splenectomy, for chronic immune thrombocytopenia (ITP). In Japan, we have developed a diagnostic system using high-throughput DNA sequencing with a multigene panel and established a registry. Between 2018 and 2023, 245 patients were enrolled and analyzed. Pathogenic variants in 17 genes (42 MYH9, 19 ANKRD26, 17 ITGA2B/ITGB3, 8 ACTN1, 8 WAS, 6 ETV6, 6 VWF, 5 CYCS, and 14 others) were identified in 125 patients (51.0%). An additional 29 patients (11.8%) had suspected pathogenic variants under investigation. We also found that immature platelet fraction (IPF%) is useful in the differential diagnosis because the median IPF% in MYH9 disorders, 48.7%, was significantly higher than in all other groups (chronic ITP, 13.4%; controls, 2.6%). The results of this study provide new insight into congenital thrombocytopenia/platelet disorders.

Can Blood Inflammatory Markers Identify Pregnant Women with Preeclampsia? Still a Controversial Issue.

BACKGROUND: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus. OBJECTIVES: To verify the efficacy of peripheral blood inflammatory markers (BIMs)in diagnosing preeclampsia and compare them with results from other studies. METHODS: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis. RESULTS: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did differentiate between study and control groups. CONCLUSIONS: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma.

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

The impact of depression on platelet activation, cardiocerebral vascular events and arteriovenous fistula dysfunction in patients undergoing haemodialysis.

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.

The potential utilization of platelet-derived extracellular vesicles in clinical treatment.

Platelet-derived extracellular vesicles (PEVs) are released by platelets in the blood circulation, which carry a rich bio-molecular cargo influential in intercellular communications. PEVs can enter the lymph, bone marrow, and synovial fluid as nano-sized particles, while platelets cannot cross tissue barriers. Considering the advantages of PEVs such as low immunogenicity, high regulation of signal transduction, and easy obtainment, PEVs may be promising therapeutic tools for medical applications. The exceptional functional roles played by PEVs explain the recent interest in exploring new cell-free therapies that could address needs in angiogenesis, regenerative medicine, and targeted drug delivery. The review takes a critical look at the main advances of PEVs in the treatment of diseases by presenting the latest knowledge from the performed studies, in order to enhance the further translation of the PEVs research into feasible therapeutic applications.

PEVs, derived from platelets, account for the most abundant proportion of all the EVs population found in the plasma. PEVs have drawn much attention due to their significance in intercellular communication and interaction by transporting a variety of molecular cargo. In the review, we summarized the therapeutic potential of PEVs for medical applications, such as cardiovascular diseases, inflammation, regenerative medicine, and targeted drug delivery. Changes in bio-active molecules in PEVs are linked to different agonists and activation methods, and further research on the mechanisms of various PEVs will allow for a new understanding of the development of PEVs as clinical therapeutic products.

Clinical Significance of Platelet Indices (Mean Platelet Volume and Mean Platelet Volume-to-lymphocyte Ratio) in Acute Coronary Syndrome: A Hospital-based Observational Study.

BACKGROUND: The role of platelet indices, such as mean platelet volume (MPV) and MPV-to-lymphocyte ratio (MPVLR), in diagnosing, and predicting the severity, and fatality in acute coronary syndrome (ACS) has not been extensively studied, particularly in Indian patients. Therefore, the study aimed to investigate the clinical significance of MPV and MPVLR in ACS. MATERIALS AND METHODS: This hospital-based observational study was conducted from 2020 to 2022. It included 110 ACS cases and an equal number of age- and sex-matched controls with chest pain of noncardiac origin. The primary objective was to compare MPV and MPVLR in ACS patients and controls. Secondary objectives included examining the associations between MPV, MPVLR, and different ACS types, as well as their correlation with the global registry of acute coronary events (GRACE) risk score and inhospital major adverse cardiovascular events (MACE). RESULTS: Higher MPV and MPVLR were observed in ACS cases compared to controls [(11.1 ± 1.1 fL; 10.6 ± 1.3 fL, p < 0.01), (7.63 ± 4.9 fL/mm3; 4.74 ± 1.6 fL/mm3, p < 0.01) respectively]. Significant associations were found between platelet indices (MPV, MPVLR) and various ACS types (p < 0.01). Both indices positively correlated with the severity of heart failure, GRACE score, and inhospital MACE (p < 0.01). MPVLR showed a positive correlation with the duration of hospital stay [(r: 0.21; p = 0.03), but MPV did not (r: 0.13; p = 0.17)]. The GRACE score demonstrated the highest discriminating capacity in predicting inhospital mortality compared to platelet indices. Additionally, MPV serves as a more effective prognostic marker than MPVLR in predicting inhospital mortality. CONCLUSION: Both MPV and MPVLR are higher in ACS than in healthy individuals. Therefore, both may be used as discriminating markers for differentiating cardiac and noncardiac chest pain when cardiac biomarkers are not available. Additionally, both have good sensitivity for predicting the severity of the disease, inhospital mortality, and MACE in ACS.

Correlation Between Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio with Risk Stratification Indicators and Thrombus Burden in Patients with Moderate-to-High Risk Acute Pulmonary Embolism, and Changes After Treatment.

OBJECTIVE: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. METHODS: This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. RESULTS: The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). CONCLUSION: Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.