Platelets最新文献

Coagulation disturbances are major contributors to COVID-19 pathogenicity, but limited data exist on the involvement of extracellular vesicles (EVs) and residual cells (RCs). Fifty hospitalized COVID-19 patients stratified by their D-dimer levels into high (>1.5 mg/L, n = 15) or low (≤1.5 mg/l, n = 35) and 10 healthy controls were assessed for medium-sized EVs (mEVs; 200-1000 nm) and large EVs/RCs (1000-4000 nm) by high sensitivity flow cytometry. EVs were analyzed for CD61, CD235a, CD45, and CD31, commonly used to detect platelets, red blood cells, leukocytes or endothelial cells, respectively, whilst phosphatidyl serine EVs/RCs were detected by lactadherin-binding implicating procoagulant catalytic surface. Small EV detection (sEVs; 50-200 nm) and CD41a (platelet integrin) colocalization with general EV markers CD9, CD63, and CD81 were performed by single particle interferometric reflectance imaging sensor. Patients with increased D-dimer exhibited the highest number of RCs and sEVs irrespective of cell origin (p < .05). Platelet activation, reflected by increased CD61+ and lactadherin+ mEV and RC levels, associated with coagulation disturbances. Patients with low D-dimer could be discriminated from controls by tetraspanin signatures of the CD41a+ sEVs, suggesting the changes in the circulating platelet sEV subpopulations may offer added prognostic value during COVID progression.

Previous studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT levels were measured prior to cancer diagnosis. We adopted overall survival (OS) as the primary outcome. Cox models were utilized to estimate the effects of PLTs on survival outcomes at multiple lag times for cancer diagnosis. We employed 34 genetic variants as PLT proxies for MR analysis. Linear and non-linear effects were modeled. Prognostic effects of gene expression harboring the instrumental variants were also investigated. A total of 65 471 cancer patients were included. We identified a significant association between elevated PLTs (per 100 × 10⁹/L) and inferior OS (HR: 1.07; 95% CI: 1.04-1.10; p < .001). Similar significant associations were observed for several cancer types. We further observed a U-shaped relationship between PLTs and cancer survival (p < .001). Our MR analysis found null evidence to support a causal association between PLTs and overall cancer survival (HR: 1.000; 95% CI: 0.998-1.001; p = .678), although non-linear MR analysis unveiled a potential greater detrimental effect at lower PLT range. Expression of eleven PLT-related genes were associated with cancer survival. Early detection of escalated PLTs indicated possible occult cancer development and inferior subsequent survival outcomes. The observed associations could potentially be non-linear. However, PLT is less likely to be a promising therapeutic target.

Background: Platelet-rich plasma (PRP) is a therapeutic approach that is gaining attention for its potential in the treatment of poor ovarian response. This meta-analysis aimed to systematically review and analyze clinical studies to evaluate the impact of PRP on poor responders undergoing ovarian stimulation for IVF.

Methods: A comprehensive search was conducted in electronic databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify relevant studies published in English. The pooled data, such as pregnancy outcome, number of MII oocytes, number of transferable embryos, and ovarian reserve markers were analyzed using R version 4.2.3.

Results: A total of 10 trials were enrolled in the present meta-analysis. Following PRP treatment, live birth rate was found to be 16.6% (95% CI 8.8%-26.1%), while clinical pregnancy rate was observed to be 25.4% (95% CI 13.1%-39.9%). PRP pretreatment resulted in a higher number of MII oocytes (MD 1.073, 95% CI 0.720 to 1.427), a higher number of embryos (MD 0.946, 95% CI 0.569 to 1.323), a higher antral follicle count (MD 1.117; 95% CI 0.689 to 1.544), and the change of hormone levels.

Conclusions: Among the studies evaluated in this review, PRP showed promising results in poor responder. Further research is required to clarify the potential role of PRP in female reproductive health.

Hemolysis is associated with thrombosis and vascular dysfunction, which are the pathological components of many diseases. Hemolytic products, including hemoglobin and hemin, activate platelets (PLT). Despite its activation, the effect of hemolysis on platelet clearance remains unclear, It is critical to maintain a normal platelet count and ensure that circulating platelets are functionally viable. In this study, we used hemin, a degradation product of hemoglobin, as a potent agonist to treat platelets and simulate changes in vivo in mice. Hemin treatment induced activation and morphological changes in platelets, including an increase in intracellular Ca²⁺ levels, phosphatidylserine (PS) exposure, and cytoskeletal rearrangement. Fewer hemin-treated platelets were cleared by macrophages in the liver after transfusion than untreated platelets. Hemin bound to glycoprotein Ibα (GPIbα), the surface receptor in hemin-induced platelet activation and aggregation. Furthermore, hemin decreased GPIbα desialylation, as evidenced by reduced Ricinus communis agglutinin I (RCA- I) binding, which likely extended the lifetime of such platelets in vivo. These data provided new insight into the mechanisms of GPIbα-mediated platelet activation and clearance in hemolytic disease.

Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a specific diagnostic test. New findings in the pathology and the availability of new drugs have led to the development of different guidelines worldwide. In the present study, the Delphi methodology has been used to get a consensus on the management of adult patients with ITP in Spain and to help in decision-making. The Delphi questionnaire has been designed by a scientific ad hoc committee and has been divided into 13 topics, with a total of 127 items, covering the maximum possible scenarios for the management of ITP. As a result of the study, a total consensus of 81% has been reached. It is concluded that this Delphi consensus provides practical recommendations on topics related to diagnosis and management of ITP patients to help doctors to improve outcomes. Some aspects remain unclear, without consensus among the experts. Thus, more advances are needed to optimize ITP management.

The last decade has seen increasing use of advanced imaging techniques in platelet research. However, there has been a lag in the development of image analysis methods, leaving much of the information trapped in images. Herein, we present a robust analytical pipeline for finding and following individual platelets over time in growing thrombi. Our pipeline covers four steps: detection, tracking, estimation of tracking accuracy, and quantification of platelet metrics. We detect platelets using a deep learning network for image segmentation, which we validated with proofreading by multiple experts. We then track platelets using a standard particle tracking algorithm and validate the tracks with custom image sampling - essential when following platelets within a dense thrombus. We show that our pipeline is more accurate than previously described methods. To demonstrate the utility of our analytical platform, we use it to show that in vivo thrombus formation is much faster than that ex vivo. Furthermore, platelets in vivo exhibit less passive movement in the direction of blood flow. Our tools are free and open source and written in the popular and user-friendly Python programming language. They empower researchers to accurately find and follow platelets in fluorescence microscopy experiments.

Acquired disorders of platelet function are an underdiagnosed cause of bleeding tendency. A 14-year-old girl developed moderate mucocutaneous bleeding two weeks after a Mycoplasma pneumoniae infection successfully treated with clarithromycin. The patient was referred to us 7 months later for laboratory investigation of the persisting bleeding diathesis. The patient's personal and family histories were negative for bleeding disorders. Complete blood count, von Willebrand Factor levels and coagulation tests were normal; platelet aggregation, ATP secretion, δ-granules content and serum thromboxane B2 levels were defective. At follow-up visits, laboratory parameters and the bleeding diathesis progressively normalized within 2 years. The patient's condition is compatible with a diagnosis of acquired Storage Pool Deficiency (SPD), associated with defective thromboxane A2 production. To our knowledge, this is the first case of acquired, transient SPD with spontaneous remission. The pathogenic role of Mycoplasma pneumoniae infection or clarithromycin is possible, albeit uncertain.

Small molecule drugs play a major role in the study of human platelets. Effective action of a drug requires it to bind to one or more targets within the platelet (target engagement). However, although in vitro assays with isolated proteins can be used to determine drug affinity to these targets, additional factors affect target engagement and its consequences in an intact platelet, including plasma membrane permeability, intracellular metabolism or compartmentalization, and level of target expression. Mechanistic interpretation of the effect of drugs on platelet activity requires comprehensive investigation of drug binding in the proper cellular context, i.e. in intact platelets. The Cellular Thermal Shift Assay (CETSA) is a valuable method to investigate target engagement within complex cellular environments. The assay is based on the principle that drug binding to a target protein increases that protein's thermal stability. In this technical report, we describe the application of CETSA to platelets. We highlight CETSA as a quick and informative technique for confirming the direct binding of drugs to platelet protein targets, providing a platform for understanding the mechanism of action of drugs in platelets, and which will be a valuable tool for investigating platelet signaling and function.

Horizontal platelet-rich fibrin (H-PRF) contains a variety of bioactive growth factors and cytokines that play a key role in the process of tissue healing and regeneration. The blood collection tubes used to produce Solid-PRF (plasmatrix (PM) tubes) have previously been shown to have a great impact on the morphology, strength and composition of the final H-PRF clot. Therefore, modification to PM tubes is an important step toward the future optimization of PRF. To this end, we innovatively modified the inner wall surface of the PM tubes with plasma and adjusted the gas environment inside the PM tubes to prepare super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes). It was made anaerobic for the preparation of H-PRF with the aim of improving mechanical strength and bioactivity. The findings demonstrated that an anaerobic environment stimulated platelet activation within the PRF tubes. After compression, the prepared H-PRF membrane formed a fibrous cross-linked network with high fracture strength, ideal degradation characteristics, in addition to a significant increase in size. Thereafter, the H-PRF membranes prepared by the SHAP tubes significantly promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts while maintaining excellent biocompatibility, and advantageous antibacterial properties. In conclusion, the newly modified PRF tubes had better platelet activation properties leading to better mechanical strength, a longer degradation period, and better regenerative properties in oral cell types including gingival fibroblast and alveolar osteoblasts. It also improves the success rate of H-PRF preparation in patients with coagulation dysfunction and expands the clinical application scenario.