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Blood Advances Oct 2023Blood platelets undergo several successive motor-driven reorganizations of the cytoskeleton when they are recruited to an injured part of a vessel. These reorganizations...
Blood platelets undergo several successive motor-driven reorganizations of the cytoskeleton when they are recruited to an injured part of a vessel. These reorganizations take place during the platelet activation phase, the spreading process on the injured vessel or between fibrin fibers of the forming clot, and during clot retraction. All these steps require a lot of energy, especially the retraction of the clot when platelets develop strong forces similar to those of muscle cells. Platelets can produce energy through glycolysis and mitochondrial respiration. However, although resting platelets have only 5 to 8 individual mitochondria, they produce adenosine triphosphate predominantly via oxidative phosphorylation. Activated, spread platelets show an increase in size compared with resting platelets, and the question arises as to where the few mitochondria are located in these larger platelets. Using expansion microscopy, we show that the number of mitochondria per platelet is increased in spread platelets. Live imaging and focused ion beam-scanning electron microscopy suggest that a mitochondrial fission event takes place during platelet activation. Fission is Drp1 dependent because Drp1-deficient platelets have fused mitochondria. In nucleated cells, mitochondrial fission is associated with a shift to a glycolytic phenotype, and using clot retraction assays, we show that platelets have a more glycolytic energy production during clot retraction and that Drp1-deficient platelets show a defect in clot retraction.
Topics: Platelet Activation; Blood Platelets; Clot Retraction; Oxidative Phosphorylation; Mitochondria
PubMed: 37624769
DOI: 10.1182/bloodadvances.2023010423 -
International Journal of Molecular... Aug 2023The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines,... (Review)
Review
The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines, chemokines, and other biological biomolecules. In recent years, developments in the field of platelets have led to new insights, and attention has been focused on the platelets' released extracellular vesicles (EVs) and their role in intercellular communication. In this context, the aim of this review was to compile the current evidence on PRP-derived extracellular vesicles to identify the advantages and limitations fortheir use in the upcoming clinical applications. A total of 172 articles were identified during the systematic literature search through two databases (PubMed and Web of Science). Twenty publications met the inclusion criteria and were included in this review. According to the results, the use of PRP-EVs in the clinic is an emerging field of great interest that represents a promising therapeutic option, as their efficacy has been demonstrated in the majority of fields of applications included in this review. However, the lack of standardization along the procedures in both the field of PRP and the EVs makes it extremely challenging to compare results among studies. Establishing standardized conditions to ensure optimized and detailed protocols and define parameters such as the dose or the EV origin is therefore urgent. Further studies to elucidate the real contribution of EVs to PRP in terms of composition and functionality should also be performed. Nevertheless, research on the field provides promising results and a novel basis to deal with the regenerative medicine and drug delivery fields in the future.
Topics: Blood Platelets; Cell Communication; Extracellular Vesicles; Platelet-Rich Plasma; Regenerative Medicine
PubMed: 37685849
DOI: 10.3390/ijms241713043 -
Frontiers in Immunology 2023In November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of...
INTRODUCTION
In November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transmission. Although Omicron has caused a significant number of deaths worldwide, it generally induces less severe clinical signs compared to earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior in severe patients infected with Omicron in comparison to Delta.
METHODS
Clinical and biological characteristics of severe COVID-19 patients infected with the Omicron (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging and electron microscopy, we examined platelet activation, responsiveness and phenotype, presence of virus in platelets and induction of selective autophagy. We also explored the direct effect of spike proteins from the Omicron or Delta variants on healthy platelet signaling.
RESULTS
Severe Omicron variant infection resulted in platelet activation and partial desensitization, presence of the virus in platelets and selective autophagy response. The intraplatelet processing of Omicron viral cargo was different from Delta as evidenced by the distribution of spike protein-positive structures near the plasma membrane and the colocalization of spike and Rab7. Moreover, spike proteins from the Omicron or Delta variants alone activated signaling pathways in healthy platelets including phosphorylation of AKT, p38MAPK, LIMK and SPL76 with different kinetics.
DISCUSSION
Although SARS-CoV-2 Omicron has different biological characteristics compared to prior variants, it leads to platelet activation and desensitization as previously observed with the Delta variant. Omicron is also found in platelets from severe patients where it induces selective autophagy, but the mechanisms of intraplatelet processing of Omicron cargo, as part of the innate response, differs from Delta, suggesting that mutations on spike protein modify virus to platelet interactions.
Topics: Humans; Blood Platelets; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Pandemics; COVID-19
PubMed: 37828997
DOI: 10.3389/fimmu.2023.1231576 -
Medicine Oct 2023Our aim was to determine the laboratory parameters that distinguish pseudothrombocytopenia from true thrombocytopenia. A total of 107 patients who were referred to the...
Our aim was to determine the laboratory parameters that distinguish pseudothrombocytopenia from true thrombocytopenia. A total of 107 patients who were referred to the adult hematology outpatient clinic with thrombocytopenia and subsequently diagnosed with acute myeloid leukaemia, immune thrombocytopenia and pseudothrombocytopenia were included in our study. Hemogram parameters on admission, platelet value in the control hemogram and peripheral smear findings were recorded. Forty three (40.2%) males and 64 (59.8%) females, were included in our study. There were 25 patients in the leukaemia group, 39 in the immune thrombocytopenia group and 43 in the pseudothrombocytopenia group. Control platelet value and red cell distribution width/platelet ratio were found to be statistically significantly different between the 3 groups. Receiver operating characteristic analysis based on platelet values showed that platelet value ≤ 38,000/µL (86% sensitivity, 78.1% specificity, P < .001), difference between 2 consecutively measured platelet levels ≤ 11. 000/µL (79.1% sensitivity, 79.7% specificity, P < .001), red cell distribution width/platelet ratio ≥ 0.413 (90.7% sensitivity, 78.1% specificity, P < .001) were found to be in favor of true thrombocytopenia. In the differentiation of pseudothrombocytopenia and true thrombocytopenia, the difference between the hemogram parameters at the time of admission and the platelet count in the control blood count may be guiding. This result may reduce patient and physician anxiety and prevent patient referral.
Topics: Adult; Male; Female; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Platelet Count; Blood Platelets; Blood Cell Count; Edetic Acid; Platelet Aggregation
PubMed: 37832120
DOI: 10.1097/MD.0000000000035395 -
Platelets Dec 2023Ischemic cardiovascular and venous thromboembolic events are a frequent cause of death in severe COVID-19 patients. Platelet activation plays a key role in these...
Ischemic cardiovascular and venous thromboembolic events are a frequent cause of death in severe COVID-19 patients. Platelet activation plays a key role in these complications, however platelet lipidomics have not been studied yet. The aim of our pilot investigation was to perform a preliminary study of platelet lipidomics in COVID-19 patients compared to healthy subjects. Lipid extraction and identification of ultrapurified platelets from eight hospitalized COVID-19 patients and eight age- and sex-matched healthy controls showed a lipidomic pattern almost completely separating COVID-19 patients from healthy controls. In particular, a significant decrease of ether phospholipids and increased levels of ganglioside GM3 were observed in platelets from COVID-19 patients. In conclusion, our study shows for the first time that platelets from COVID-19 patients display a different lipidomics signature distinguishing them from healthy controls, and suggests that altered platelet lipid metabolism may play a role in viral spreading and in the thrombotic complications of COVID-19.
Topics: Humans; COVID-19; Lipidomics; Blood Platelets; Platelet Activation; Thrombosis
PubMed: 37114418
DOI: 10.1080/09537104.2023.2200847 -
Platelets Dec 2023F11 receptor (F11R)/Junctional Adhesion Molecule -A (JAM-A) is a transmembrane protein which belongs to the immunoglobulin superfamily of cell adhesion molecules.... (Review)
Review
F11 receptor (F11R)/Junctional Adhesion Molecule -A (JAM-A) is a transmembrane protein which belongs to the immunoglobulin superfamily of cell adhesion molecules. F11R/JAM-A is present in epithelial cells, endothelial cells, leukocytes, and blood platelets. In epithelial and endothelial cells, it takes part in the formation of tight junctions. In these structures, molecules of F11R/JAM-A located on adjacent cells form homodimers and thus take part in stabilization of cellular layer integrity. In leukocytes, F11R/JAM-A was shown to play role in their transmigration through the vascular wall. Paradoxically, the function of F11R/JAM-A in blood platelets, where it was primarily discovered, is much less understood. It has been proven to regulate downstream signaling of αIIbβ3 integrin and to mediate platelet adhesion under static conditions. It was also shown to contribute to transient interactions of platelets with inflamed vascular wall. The review is aimed at summarizing the current state of knowledge of the platelet pool of F11R/JAM-A. The article also presents perspectives of the future research to better understand the role of this protein in hemostasis, thrombosis, and other processes where blood platelets are involved.
Topics: Humans; Blood Platelets; Junctional Adhesion Molecule A; Endothelial Cells; Tight Junctions; Cell Adhesion Molecules; Receptors, Cell Surface
PubMed: 37246517
DOI: 10.1080/09537104.2023.2214618 -
Journal of Clinical Laboratory Analysis Jan 2024Platelet concentrate (PC) transfusions are crucial in prevention and treatment of bleeding in infection, surgery, leukemia, and thrombocytopenia patients. Although the... (Review)
Review
BACKGROUND
Platelet concentrate (PC) transfusions are crucial in prevention and treatment of bleeding in infection, surgery, leukemia, and thrombocytopenia patients. Although the technology for platelet preparation and storage has evolved over the decades, there are still challenges in the demand for platelets in blood banks because the platelet shelf life is limited to 5 days due to bacterial contamination and platelet storage lesions (PSLs) at 20-24°C under constant horizontal agitation. In addition, the relations between some adverse effects of platelet transfusions and PSLs have also been considered. Therefore, understanding the mechanisms of PSLs is conducive to obtaining high quality platelets and facilitating safe and effective platelet transfusions.
OBJECTIVE
This review summarizes developments in mechanistic research of PSLs and their relationship with clinical practice, providing insights for future research.
METHODS
Authors conducted a search on PubMed and Web of Science using the professional terms "PSL" and "platelet transfusion." The obtained literature was then roughly categorized based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section.
RESULTS
Different studies have explored PSLs from various perspectives, including changes in platelet morphology, surface molecules, biological response modifiers (BMRs), metabolism, and proteins and RNA, in an attempt to monitor PSLs and identify intervention targets that could alleviate PSLs. Moreover, novel platelet storage conditions, including platelet additive solutions (PAS) and reconsidered cold storage methods, are explored. There are two approaches to obtaining high-quality platelets. One approach simulates the in vivo environment to maintain platelet activity, while the other keeps platelets at a low activity level in vitro under low temperatures.
CONCLUSION
Understanding PSLs helps us identify good intervention targets and assess the therapeutic effects of different PSLs stages for different patients.
Topics: Humans; Blood Platelets; Platelet Transfusion; Thrombocytopenia; Hemorrhage; Blood Banks; Blood Preservation
PubMed: 38069592
DOI: 10.1002/jcla.24994 -
International Journal of Molecular... Jul 2023Zinc (Zn) is released by platelets during a hemostatic response to injury. Extracellular zinc ([Zn]) initiates platelet activation following influx into the platelet...
Zinc (Zn) is released by platelets during a hemostatic response to injury. Extracellular zinc ([Zn]) initiates platelet activation following influx into the platelet cytosol. However, the mechanisms that permit Zn influx are unknown. Fluctuations in intracellular zinc ([Zn]) were measured in fluozin-3-loaded platelets using fluorometry and flow cytometry. Platelet activation was assessed using light transmission aggregometry. The detection of phosphoproteins was performed by Western blotting. [Zn] influx and subsequent platelet activation were abrogated by blocking the sodium/calcium exchanged, TRP channels, and ZIP7. Cation store depletion regulated Zn influx. [Zn] stimulation resulted in the phosphorylation of PKC substates, MLC, and β3 integrin. Platelet activation via GPVI or Zn resulted in ZIP7 phosphorylation in a casein kinase 2-dependent manner and initiated elevations of [Zn] that were sensitive to the inhibition of Orai1, ZIP7, or IPR-mediated pathways. These data indicate that platelets detect and respond to changes in [Zn] via influx into the cytosol through TRP channels and the NCX exchanger. Platelet activation results in the externalization of ZIP7, which further regulates Zn influx. Increases in [Zn] contribute to the activation of cation-dependent enzymes. Sensitivity of Zn influx to thapsigargin indicates a store-operated pathway that we term store-operated Zn entry (SOZE). These mechanisms may affect platelet behavior during thrombosis and hemostasis.
Topics: Cation Transport Proteins; Zinc; Endoplasmic Reticulum; Platelet Activation; Blood Platelets; Cations; Calcium
PubMed: 37511448
DOI: 10.3390/ijms241411689 -
Genes Jun 2024Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated...
Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated with increased risk for venous thromboembolism (VTE). The underlying etiology of the prothrombotic profile observed in lipedema and lymphedema is unclear, but may be related to alterations in platelets. Our objective was to analyze the platelet transcriptome to identify biological pathways that may provide insight into platelet activation and thrombosis. The platelet transcriptome was evaluated in patients with lymphedema and lipedema, then compared to control subjects with obesity. Patients with lipedema were found to have a divergent transcriptome from patients with lymphedema. The platelet transcriptome and impacted biological pathways in lipedema were surprisingly similar to weight-matched comparators, yet different when compared to overweight individuals with a lower body mass index (BMI). Differences in the platelet transcriptome for patients with lipedema and lymphedema were found in biological pathways required for protein synthesis and degradation, as well as metabolism. Key differences in the platelet transcriptome for patients with lipedema compared to BMI-matched subjects involved metabolism and glycosaminoglycan processing. These inherent differences in the platelet transcriptome warrant further investigation, and may contribute to the increased risk of thrombosis in patients with lipedema and lymphedema.
Topics: Humans; Lymphedema; Lipedema; Female; Transcriptome; Middle Aged; Blood Platelets; Male; Adult; Body Mass Index; Platelet Activation; Obesity; Case-Control Studies
PubMed: 38927673
DOI: 10.3390/genes15060737 -
Science Advances Dec 2023Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets...
Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors. Here, we describe an approach using platelet-optimized lipid nanoparticles containing mRNA (mRNA-LNP) to enable exogenous protein expression in human and rat platelets. Within the library of mRNA-LNP tested, exogenous protein expression did not require nor correlate with platelet activation. Transfected platelets retained hemostatic function and accumulated in regions of vascular damage after transfusion into rats with hemorrhagic shock. We expect this technology will expand the therapeutic potential of platelets.
Topics: Humans; Rats; Animals; RNA, Messenger; Blood Platelets; Blood Donors; Hemostatics
PubMed: 38039367
DOI: 10.1126/sciadv.adi0508