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PloS One 2019Gender influences platelet biology. Women have a larger platelet count, but gender-based differences in platelet function remain debated. We performed a study addressing...
BACKGROUND
Gender influences platelet biology. Women have a larger platelet count, but gender-based differences in platelet function remain debated. We performed a study addressing gender-based differences in platelet function using point-of-care platelet function tests (PFT).
METHODS
The patient population consisted of 760 cardiac surgery patients where preoperative PFT (multiple-electrode aggregometry [MEA]) were available. Platelet count and function at the ADPtest and TRAPtest were compared in the overall population and separately in patients with or without residual effects of P2Y12 inhibitors.
RESULTS
Women had a significantly (P = 0.001) higher platelet count but a non-significantly higher platelet reactivity to ADP. In clopidogrel-treated patients, the platelets ADP reactivity was significantly (P = 0.031) higher in women, and platelet count was the main determinant of platelet hyper-reactivity. Within patients under full clopidogrel effects, women with a platelet count ≥ 200,000 cells/μL had a significantly (P = 0.023) higher rate of high-on-treatment platelet reactivity (HTPR, 45.5%) with respect to males with a platelet count < 200,000 cells/μL (11.9%), with a relative risk of 6.2 (95% confidence interval 1.4-29).
CONCLUSIONS
Our findings confirm that women have a larger platelet count than men, and that this is associated to a trend towards a higher platelet reactivity. HTPR is largely represented in women with a high platelet count. This generates the hypothesis that women requiring P2Y12 inhibitors could potentially benefit from larger doses of drug or should be treated with anti-platelet agents with a low rate of HTPR.
Topics: Adenosine Diphosphate; Aged; Blood Platelets; Cardiac Surgical Procedures; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Count; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Sex Factors
PubMed: 31774869
DOI: 10.1371/journal.pone.0225771 -
International Journal of Molecular... Nov 2020Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the... (Review)
Review
Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D (PGD), prostaglandin-E, -E and E (PGE, PGE, PGE), prostaglandin F (PGF), prostacyclin (PGI) and thromboxane-A (TXA) on platelet activation and aggregation via their respective receptors.
Topics: Blood Platelets; Humans; Models, Biological; Platelet Aggregation; Prostaglandins; Receptors, Prostaglandin; Signal Transduction
PubMed: 33260972
DOI: 10.3390/ijms21239020 -
Journal of Veterinary Internal Medicine Mar 2023Platelet function testing in cats allows determination of clopidogrel effect. Plateletworks assesses aggregation based on decreasing platelet counts on hematology...
BACKGROUND
Platelet function testing in cats allows determination of clopidogrel effect. Plateletworks assesses aggregation based on decreasing platelet counts on hematology analyzers in response to agonists. It has not been validated for the IDEXX ProCyte Dx analyzer. Ideal time to perform analysis and the utility of other platelet parameters have not been fully assessed.
OBJECTIVES
To validate Plateletworks ADP on the ProCyte Dx, to investigate the utility of various platelet parameters using Plateletworks ADP, and determine the ideal time to perform analysis.
ANIMALS
Twenty healthy cats recruited from the general population used for transference of reference intervals to a new analyzer, and 10 cats receiving clopidogrel to determine clopidogrel effect.
METHODS
Plateletworks ADP using the ProCyte Dx and ADVIA 2120i analyzer was run simultaneously in both healthy cats and cats receiving clopidogrel, and CBC results at different timepoints were compared between analyzers.
RESULTS
Aggregation was significantly different (P < .001) between analyzers. Cohen's kappa showed almost perfect agreement for determination of clopidogrel effect, and the area under the curve of the receiver operating characteristic was 1.0. Lower limits of the aggregation reference interval in healthy cats were 28.8% on the ProCyte Dx and 12.5% on the ADVIA 2120i. Coefficients of variation for platelet parameters were not different between analyzers. No significant changes in mean platelet volume, plateletcrit, large platelets, and mean platelet component were identified. No significant change in aggregation was observed within the first hour after phlebotomy.
CONCLUSIONS AND CLINICAL IMPORTANCE
Our study validated the Plateletworks ADP system on the ProCyte Dx analyzer. Samples may be analyzed up to 1 h after collection.
Topics: Cats; Animals; Clopidogrel; Platelet Function Tests; Platelet Aggregation; Blood Platelets
PubMed: 36856192
DOI: 10.1111/jvim.16670 -
Scientific Reports Jan 2022To evaluate the effects of fructose diphosphate (FDP) on routine coagulation tests in vitro, we added FDP into the mixed normal plasma to obtain the final concentration...
To evaluate the effects of fructose diphosphate (FDP) on routine coagulation tests in vitro, we added FDP into the mixed normal plasma to obtain the final concentration of 0, 1, 2, 3, 4, 5, 6, 10, 15, 20, 25, 30 and 35 mg/mL of drug. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FBG) and thrombin time (TT) of samples were analyzed with blood coagulation analyzers from four different manufacturers(Sysmex, Stago, SEKISUI and Werfen) and their corresponding reagents, respectively. Before the experiment, we also observed whether there were significant differences in coagulation test results of different lots of reagents produced by each manufacturer. At the same time as the four routine clotting tests, the Sysmex blood coagulation analyzer and its proprietary analysis software were used to detect the change of maximum platelet aggregation rate in platelet-rich plasma after adding FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL). The results of PT, aPTT and TT showed a FDP (0-35 mg/mL) concentration-dependent increase and a FBG concentration-dependent decrease. The degree of change (increase or decrease) varied depending on the assay system, with PT and aPTT being more affected by the Sysmex blood coagulation testing instrument reagent system and less affected by CEKISUI, TT less affected by CEKISUI and more affected by Stago, and FBG less affected by Stago and more affected by Sysmex. The results of PT, aPTT and TT were statistically positively correlated with their FDP concentrations, while FBG was negatively correlated. The correlation coefficients between FDP and the coagulation testing systems of Sysmex, Stago, Werfen and SEKISUI were 0.975, 0.988, 0.967, 0.986 for PT, and 0.993, 0.989, 0.990 and 0.962 for aPTT, 0.994, 0.960, 0.977 and 0.982 for TT, - 0.990, - 0.983, - 0.989 and - 0.954 for FBG, respectively. Different concentrations of FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL) had different effects on the maximum aggregation rate of platelet induced by the agonists of adenosine diphosphate (ADP, 5 µmol/L), arachidonic acid (Ara, 1 mmol/L), collagen (Col, 2.5 µg/mL) and epinephrine (Epi,10 µmol/L), but the overall downward trend was consistent, that is, with the increase of FDP concentration, the platelet aggregation rate decreased significantly. Our experimental study demonstrated a possible effect of FDP on the assays of coagulation and Platelet aggregation, which may arise because the drug interferes with the coagulation and platelet aggregation detection system, or it may affect our in vivo coagulation system and Platelet aggregation function, the real mechanism of which remains to be further verified and studied.
Topics: Blood Coagulation; Blood Coagulation Tests; Dose-Response Relationship, Drug; Fructosediphosphates; Humans; Partial Thromboplastin Time; Platelet Aggregation; Platelet Function Tests; Prothrombin Time; Thrombin Time
PubMed: 34997135
DOI: 10.1038/s41598-021-04263-y -
Molecules (Basel, Switzerland) Jul 2023Resveratrol, a naturally occurring stilbene, exhibits numerous beneficial health effects. Various studies have demonstrated its diverse biological actions, including...
Resveratrol, a naturally occurring stilbene, exhibits numerous beneficial health effects. Various studies have demonstrated its diverse biological actions, including anti-oxidant, anti-inflammatory, and anti-platelet properties, thereby supporting its potential for cardio protection, neuroprotection, and anti-cancer activity. However, a significant limitation of resveratrol is its weak bioavailability. To overcome this challenge, multiple research groups have investigated the synthesis of new resveratrol derivatives to enhance bioavailability and pharmacological activities. Nevertheless, there are limited data on the effects of resveratrol derivatives on platelet function. Therefore, the objective of this study was to synthesize resveratrol methoxy derivatives and evaluate their anti-platelet and anti-proliferative activity. Platelet-rich plasma (PRP) obtained from healthy volunteers was utilized to assess the derivatives' ability to inhibit platelet aggregation induced by platelet activating factor (PAF), adenosine diphosphate (ADP), and thrombin receptor activating peptide (TRAP). Additionally, the derivatives' anti-tumor activity was evaluated against the proliferation of PC-3 and HCT116 cells. The results revealed that some methoxy derivatives of resveratrol exhibited comparable or even superior anti-platelet activity compared to the original compound. The most potent derivative was the 4'-methoxy derivative, which demonstrated approximately 2.5 orders of magnitude higher anti-platelet activity against TRAP-induced platelet aggregation, indicating its potential as an anti-platelet agent. Concerning in silico studies, the 4'-methyl group of 4'-methoxy derivative is oriented similarly to the fluorophenyl-pyridyl group of Vorapaxar, buried in a hydrophobic cavity. In terms of their anti-tumor activity, 3-MRESV exhibited the highest potency in PC-3 cells, while 3,4'-DMRESV and TMRESV showed the greatest efficacy in HCT116 cells. In conclusion, methoxy derivatives of resveratrol possess similar or improved anti-platelet and anti-cancer effects, thereby holding potential as bioactive compounds in various pathological conditions.
Topics: Humans; Resveratrol; Platelet Aggregation; Blood Platelets; Platelet Aggregation Inhibitors; Platelet Function Tests
PubMed: 37513418
DOI: 10.3390/molecules28145547 -
International Journal of Molecular... Jan 2023Endoprostheses are prone to tribological wear and biological processes that lead to the release of particles, including aluminum nanoparticles (Al NPs). Those particles...
Endoprostheses are prone to tribological wear and biological processes that lead to the release of particles, including aluminum nanoparticles (Al NPs). Those particles can diffuse into circulation. However, the toxic effects of NPs on platelets have not been comprehensively analyzed. The aim of our work was to investigate the impact of Al NPs on human platelet function using a novel quartz crystal microbalance with dissipation (QCM-D) methodology. Moreover, a suite of assays, including light transmission aggregometry, flow cytometry, optical microscopy and transmission electron microscopy, were utilized. All Al NPs caused a significant increase in dissipation (D) and frequency (F), indicating platelet aggregation even at the lowest tested concentration (0.5 µg/mL), except for the largest (80 nm) Al NPs. A size-dependent effect on platelet aggregation was observed for the 5-20 nm NPs and the 30-50 nm NPs, with the larger Al NPs causing smaller increases in D and F; however, this was not observed for the 20-30 nm NPs. In conclusion, our study showed that small (5-50 nm) Al NPs caused platelet aggregation, and larger (80 nm) caused a bridging-penetrating effect in entering platelets, resulting in the formation of heterologous platelet-Al NPs structures. Therefore, physicians should consider monitoring NP serum levels and platelet activation indices in patients with orthopedic implants.
Topics: Humans; Aluminum; Blood Platelets; Platelet Aggregation; Nanoparticles; Microscopy, Electron, Transmission
PubMed: 36768869
DOI: 10.3390/ijms24032547 -
Journal of the American College of... Mar 2016
Topics: Adenosine; Blood Platelets; Humans; Myocardial Infarction; Platelet Aggregation; Purinergic P2Y Receptor Antagonists
PubMed: 26965535
DOI: 10.1016/j.jacc.2015.12.061 -
Oxidative Medicine and Cellular... 2022Platelet transfusion is a life-saving therapy to prevent bleeding; however, the availability of platelets for transfusion is limited by the markedly short shelf life...
Platelet transfusion is a life-saving therapy to prevent bleeding; however, the availability of platelets for transfusion is limited by the markedly short shelf life owing to the development of platelet storage lesions (PSLs). The mechanism of PSLs remains obscure. Dissection of the intracellular biological changes in stored platelets may help to reduce PSLs and improve platelet transfusion efficiency. In the present study, we explore the changes of stored platelets at room temperature under constant agitation. We found that platelets during storage showed an increased reactive oxygen species (ROS) generation accompanied with receptor shedding, apoptosis, and diminished platelet aggregation. ROS scavenger reduced platelet shedding but also impaired platelet aggregation. Autophagy is a conserved catabolic process that sequesters protein aggregates and damaged organelles into lysosomes for degradation and platelets' own intact autophagic system. We revealed that there exist a stable autophagic flux in platelets at the early stage of storage, and the autophagic flux in platelets perished after long-term storage. Treatment stored platelets with rapamycin, which stimulates autophagy in eukaryotic cells, markedly ameliorated PSLs, and improved platelet aggregation in response to extracellular stimuli.
Topics: Autophagy; Blood Platelets; Platelet Aggregation; Platelet Transfusion; Reactive Oxygen Species
PubMed: 36046681
DOI: 10.1155/2022/1898844 -
Journal of Thrombosis and Haemostasis :... Apr 2020In the intact vessel wall, endothelial cells form a barrier between the blood and the remaining vascular structures, serving to maintain blood fluidity and preventing...
BACKGROUND
In the intact vessel wall, endothelial cells form a barrier between the blood and the remaining vascular structures, serving to maintain blood fluidity and preventing platelet activation and fibrin clot formation. The spatiotemporal space of this inhibition is largely unknown.
OBJECTIVE
To assess the local inhibitory roles of a discontinuous endothelium, we developed a vessel-on-a-chip model, consisting of a microfluidic chamber coated with the thrombogenic collagen and tissue factor (TF), and covered with patches of human endothelial cells. By flow perfusion of human blood and plasma, the heterogeneous formation of platelet aggregates and fibrin clots was monitored by multicolor fluorescence microscopy.
RESULTS
On collagen/TF coatings, a coverage of 40% to 60% of human umbilical vein endothelial cells resulted in a strong overall delay in platelet deposition and fibrin fiber formation under flow. Fibrin formation colocalized with the deposited platelets, and was restricted to regions in between endothelial cells, thus pointing to immediate local suppression of the clotting process. Fibrin kinetics were enhanced by treatment of the cells with heparinase III, partially disrupting the glycocalyx, and to a lesser degree by antagonism of the endothelial thrombomodulin. Co-coating of purified thrombomodulin and collagen had a similar coagulation-suppressing effect as endothelial thrombomodulin.
CONCLUSIONS
In this vessel-on-a-chip system with patches of endothelial cells on thrombogenic surfaces, the coagulant activity under flow is regulated by: (a) the residual exposure of trigger (collagen/TF), (b) the endothelial glycocalyx, and (c) to a lesser degree the endothelial thrombomodulin.
Topics: Blood Coagulation; Blood Platelets; Endothelial Cells; Endothelium; Humans; Lab-On-A-Chip Devices; Platelet Aggregation
PubMed: 31863548
DOI: 10.1111/jth.14719 -
Biomechanics and Modeling in... Jun 2021We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low-intermediate shear viscous flow, in which aggregation is mediated...
We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low-intermediate shear viscous flow, in which aggregation is mediated by the interaction of αβ receptors on the platelet membrane and fibrinogen (Fg). This multiscale model uses coarse grained molecular dynamics (CGMD) for platelets at the microscales and dissipative particle dynamics (DPD) for the shear flow at the macroscales, employing our hybrid aggregation force field for modeling molecular level receptor ligand bonds. We define an aggregation tensor and use it to quantify the molecular level contact characteristics between platelets in an aggregate. We perform numerical studies under different flow conditions for platelet doublets and triplets and evaluate the contact area, detaching force and minimum distance between different pairs of platelets in an aggregate. We also present the dynamics of applied stress and velocity magnitude distributions on the platelet membrane during aggregation and quantify the increase in stress in the contact region under different flow conditions. Integrating the knowledge from our previously validated models, together with new aggregation scenarios, our model can dynamically quantify aggregation characteristics and map stress and velocity distribution on the platelet membrane which are difficult to measure in vitro, thus providing an insight into mechanotransduction bond formation response of platelets to flow-induced shear stresses. This modeling framework, together with the tensor method for quantifying inter-platelet contact, can be extended to simulate and analyze larger aggregates and their adhesive properties.
Topics: Blood Platelets; Computer Simulation; Humans; Models, Biological; Numerical Analysis, Computer-Assisted; Platelet Aggregation; Rheology; Shear Strength; Stress, Mechanical
PubMed: 33782796
DOI: 10.1007/s10237-021-01428-6