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Platelets Nov 2018While there are many bench and bedside tests to assess platelet reactivity, ex vivo light transmission aggregometry (LTA) remains the gold standard. LTA, however, is... (Review)
Review
While there are many bench and bedside tests to assess platelet reactivity, ex vivo light transmission aggregometry (LTA) remains the gold standard. LTA, however, is expensive, time-consuming and requires dedicated equipment and staff, making it impractical in many situations. In addition, there is significant variability between data generated at different testing sites meaning that tests often need to be repeated if a patient is transferred to the care of a different hospital. As such, there is clearly an unmet need for standardization of platelet testing. Using the principles of LTA, aggregometry can be conducted in 96-well plates with readings being made in a standard plate reader. This approach allows for the assessment of multiple concentrations of agonists, since the volume of platelets required for each test is significantly lower than for LTA. Furthermore, the lyophilization of a set panel of agonists to a 96-well plate to produce a stable assay substrate allows the production of portable, standardized plates that can be used to generate reproducible tests at multiple sites. In this review, we will discuss the methods and uses of 96-well plate aggregometry for both research and the clinic.
Topics: Animals; Humans; Platelet Aggregation; Platelet Function Tests; Research
PubMed: 29543546
DOI: 10.1080/09537104.2018.1445838 -
Seminars in Cell & Developmental Biology Apr 2021The ability to study the behavior of cells, proteins, and cell-cell or cell-protein interactions under dynamic forces such as shear stress under fluid flow, provides a... (Review)
Review
The ability to study the behavior of cells, proteins, and cell-cell or cell-protein interactions under dynamic forces such as shear stress under fluid flow, provides a more accurate understanding of the physiopathology of hemostasis. This review touches upon the traditional methods for studying blood coagulation and platelet aggregation and provides an overview on cellular and protein response to shear stress. We also elaborate on the biological aspects of how cells recognize mechanical forces and convert them into biochemical signals that can drive various signaling pathways. We give a detailed description of the various types of microfluidic devices that are employed to study the complex processes of platelet aggregation and blood coagulation under flow conditions as well as to investigate endothelial shear-response. We also highlight works mimicking artificial vessels as platforms to study the mechanisms of coagulation, and finish our review by describing anticipated clinical uses of microfluidics devices and their standardization.
Topics: Blood Coagulation; Hemostasis; Humans; Lab-On-A-Chip Devices; Platelet Aggregation; Signal Transduction; Thrombosis
PubMed: 32563678
DOI: 10.1016/j.semcdb.2020.06.002 -
British Journal of Clinical Pharmacology Oct 2011Inhibition of platelet aggregation can be achieved either by the blockade of membrane receptors or by interaction with intracellular signalling pathways. Cyclic... (Review)
Review
Inhibition of platelet aggregation can be achieved either by the blockade of membrane receptors or by interaction with intracellular signalling pathways. Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) are two critical intracellular second messengers provided with strong inhibitory activity on fundamental platelet functions. Phosphodiesterases (PDEs), by catalysing the hydrolysis of cAMP and cGMP, limit the intracellular levels of cyclic nucleotides, thus regulating platelet function. The inhibition of PDEs may therefore exert a strong platelet inhibitory effect. Platelets possess three PDE isoforms (PDE2, PDE3 and PDE5), with different selectivity for cAMP and cGMP. Several nonselective or isoenzyme-selective PDE inhibitors have been developed, and some of them have entered clinical use as antiplatelet agents. This review focuses on the effect of PDE2, PDE3 and PDE5 inhibitors on platelet function and on the evidence for an antithrombotic action of some of them, and in particular of dipyridamole and cilostazol.
Topics: Blood Platelets; Cilostazol; Clinical Trials as Topic; Dipyridamole; Humans; Phosphodiesterase Inhibitors; Platelet Aggregation; Platelet Aggregation Inhibitors; Tetrazoles; Thrombosis
PubMed: 21649691
DOI: 10.1111/j.1365-2125.2011.04034.x -
Arteriosclerosis, Thrombosis, and... May 2019
Topics: Platelet Aggregation; Platelet Membrane Glycoproteins
PubMed: 31017825
DOI: 10.1161/ATVBAHA.119.312621 -
Haematologica Feb 2022
Topics: Blood Platelets; Humans; Platelet Aggregation; Platelet Function Tests
PubMed: 35100793
DOI: 10.3324/haematol.2021.280198 -
British Journal of Clinical Pharmacology Nov 2014Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect... (Meta-Analysis)
Meta-Analysis Review
AIMS
Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect platelet aggregation, because β-adrenergic receptors are present on platelets. There is uncertainty about the existence and magnitude of an effect of β-blockers on platelet aggregation. The aim of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on platelet aggregation.
METHODS
MEDLINE and EMBASE were searched until April 2014. Two reviewers independently performed data extraction and risk of bias assessment. Type of β-blocker, population, treatment duration and platelet aggregation were extracted. Standardized mean differences were calculated for each study and pooled in a random-effects meta-analysis.
RESULTS
We retrieved 31 studies (28 clinical trials and three observational studies). β-Blockers decreased platelet aggregation (standardized mean difference -0.54, 95% confidence interval -0.85 to -0.24, P < 0.0001). This corresponds to a reduction of 13% (95% confidence interval 8-17%). Nonselective lipophilic β-blockers decreased platelet aggregation more than selective nonlipophilic β-blockers.
CONCLUSIONS
Clinically used β-blockers significantly reduce platelet aggregation. Nonselective lipophilic β-blockers seem to reduce platelet aggregation more effectively than selective nonlipophilic β-blockers. These findings may help to explain why some β-blockers are more effective than others in preventing cardiovascular disease.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Observational Studies as Topic; Platelet Aggregation
PubMed: 24730697
DOI: 10.1111/bcp.12404 -
Scientific Reports Apr 2019Although reversible platelet aggregation observed in response to ADP stimulation in the presence of calcium is a well-known phenomenon, its mechanisms are not entirely...
Although reversible platelet aggregation observed in response to ADP stimulation in the presence of calcium is a well-known phenomenon, its mechanisms are not entirely clear. To study them, we developed a simple kinetic mass-action-law-based mathematical model to use it in combination with experiments. Light transmission platelet aggregometry (LTA) induced by ADP was performed for platelet-rich plasma or washed platelets using both conventional light transmission and aggregate size monitoring method based on optical density fluctuations. Parameter values of the model were determined by means of parameter estimation techniques implemented in COPASI software. The mathematical model was able to describe reversible platelet aggregation LTA curves without assuming changes in platelet aggregation parameters over time, but with the assumption that platelet can enter the aggregate only once. In the model, the mean size of platelet aggregates correlated with the solution transparency. This corresponded with flow cytometry analysis and with optical density fluctuations data on aggregate size. The predicted values of model parameters correlated with ADP concentration used in experiments. These data suggest that, at the start of the aggregation, when platelet integrins switch "on", large unstable platelet aggregates are rapidly formed, which leads to an increase in light transmission. However, upon fragmentation of these aggregates, the probability of the post-aggregate platelets' attachment to each other decreases preventing new aggregation and resulting in the reversible aggregation phenomenon.
Topics: Adenosine Diphosphate; Adolescent; Adult; Blood Platelets; Female; Flow Cytometry; Healthy Volunteers; Humans; Kinetics; Light; Male; Models, Theoretical; Platelet Aggregation; Platelet Function Tests; Scattering, Radiation; Software; Young Adult
PubMed: 30996289
DOI: 10.1038/s41598-019-42701-0 -
International Journal of Molecular... Aug 2017Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic... (Review)
Review
Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.
Topics: Blood Platelets; Humans; Platelet Adhesiveness; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Reproducibility of Results; Sensitivity and Specificity; Thrombosis; Ticlopidine
PubMed: 28820484
DOI: 10.3390/ijms18081803 -
Journal of Experimental & Clinical... Oct 2023Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a...
BACKGROUND
Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a low response to immune checkpoint inhibitors (ICIs) in hematogenous metastasis of malignant melanoma (MM). However, there is no TCIPA-specific model for further investigation of the relationship among TCIPA, the tumor immune microenvironment (TIME), and metastasis.
METHODS
We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME.
RESULTS
We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1β. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis.
CONCLUSIONS
TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.
Topics: Humans; Platelet Aggregation; Melanoma; Lung Neoplasms; Macrophages; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 37872588
DOI: 10.1186/s13046-023-02856-1 -
Blood Nov 1983
Topics: Aspirin; Firefly Luciferin; Humans; Luciferases; Platelet Aggregation
PubMed: 6626747
DOI: No ID Found