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Clinical Hemorheology and... 2021Major burn injury causes massive tissue destruction consequently enhanced platelet function and leukocyte-mediated inflammatory response.
BACKGROUND
Major burn injury causes massive tissue destruction consequently enhanced platelet function and leukocyte-mediated inflammatory response.
METHODS
In a prospective, observational study 23 consecutive patients with more than 20% body surface burn injury were followed for five days (T1-T5) after admission to a university intensive care (ICU). Platelet and leukocyte antisedimentation rate (PAR and LAR) was measured by one-hour gravity sedimentation. It detects the percentage of total platelet and leukocyte number crossed the half line of blood sample column, therefore, they can be regarded as cells of decreased specific gravity. We aimed to investigate the time course of PAR and LAR after burn injury, as the trend of platelet and the leukocyte activation in the early post-burn period.
RESULTS
Daily mean PAR and LAR values continuously increased in the observation period (T1 to T5). Daily mean PAR and LAR were lower in ICU non-survivors (n = 7) compared to survivors (n = 16) between T2 and T4 (p < 0.05 and p < 0.01). PAR values of septic patients (n = 10) were lower than that of non-septic ones (n = 13, p < 0.01 at T5).
CONCLUSIONS
Both PAR and LAR, as novel bedside test can predict septic complications and unfavorable outcome after major burn injury. Further studies with higher sample size are warranted.
Topics: Blood Platelets; Burns; Female; Humans; Leukocytes; Male; Middle Aged; Platelet Activation; Prospective Studies
PubMed: 32538824
DOI: 10.3233/CH-190779 -
Annales de Biologie Clinique Feb 2021During primary hemostasis the platelets aggregate to form the platelet thrombus. ADP and thrombin generated by coagulation are the main agonists in platelet aggregation....
During primary hemostasis the platelets aggregate to form the platelet thrombus. ADP and thrombin generated by coagulation are the main agonists in platelet aggregation. In a previous study we were able to show that patients with lung cancer had hypercoagulability, hyperfibrinogemia (≥ 6.22 g/L) was predictive of thromboembolic disease at the start of diagnosis before any therapy. In this study, we studied platelet aggregation in these patients in order to demonstrate whether they have hyperaggregability associated with the hypercoagulability demonstrated previously, and this by evaluating abnormalities in primary hemostasis (platelet count and platelet aggregation). One hundred and one patients diagnosed before any therapy and 72 blood donors were included. Agonists used for platelet aggregation are collagen and adenosine diphosphate at low concentrations. Hyperaggregability is observed when blood platelets are stimulated by ADP at different concentrations (p ≤ 0.01). This hyperaggregability is influenced by the histological type and not the development of the cancer, the age of the subjects and the platelet count, it is independent of hyperfibrinogemia and the occurrence of thromboembolic disease. However, an increase in the platelet level is found in patients with hyperfibrinogemia. Patients with lung cancer present platelet activation observed by aggregometry in response to ADP; which is not influenced by hyperfibrinogemia during cancer.
Topics: Adenosine Diphosphate; Blood Platelets; Humans; Lung Neoplasms; Platelet Aggregation; Thrombin
PubMed: 33648917
DOI: 10.1684/abc.2021.1623 -
Cells Oct 20211,8-cineole, a monoterpenoid is a major component of eucalyptus oil and has been proven to possess numerous beneficial effects in humans. Notably, 1,8-cineole is the...
1,8-cineole, a monoterpenoid is a major component of eucalyptus oil and has been proven to possess numerous beneficial effects in humans. Notably, 1,8-cineole is the primary active ingredient of a clinically approved drug, Soledum which is being mainly used for the maintenance of sinus and respiratory health. Due to its clinically valuable properties, 1,8-cineole has gained significant scientific interest over the recent years specifically to investigate its anti-inflammatory and antioxidant effects. However, the impact of 1,8-cineole on the modulation of platelet activation, thrombosis and haemostasis was not fully established. Therefore, in this study, we demonstrate the effects of 1,8-cineole on agonists-induced platelet activation, thrombus formation under arterial flow conditions and haemostasis in mice. 1,8-cineole largely inhibits platelet activation stimulated by glycoprotein VI (GPVI) agonists such as collagen and cross-linked collagen-related peptide (CRP-XL), while it displays minimal inhibitory effects on thrombin or ADP-induced platelet aggregation. It inhibited inside-out signalling to integrin αIIbβ3 and outside-in signalling triggered by the same integrin as well as granule secretion and intracellular calcium mobilisation in platelets. 1,8-cineole affected thrombus formation on collagen-coated surface under arterial flow conditions and displayed a minimal effect on haemostasis of mice at a lower concentration of 6.25 µM. Notably, 1,8-cineole was found to be non-toxic to platelets up to 50 µM concentration. The investigation on the molecular mechanisms through which 1,8-cineole inhibits platelet function suggests that this compound affects signalling mediated by various molecules such as AKT, Syk, LAT, and cAMP in platelets. Based on these results, we conclude that 1,8-cineole may act as a potential therapeutic agent to control unwarranted platelet reactivity under various pathophysiological settings.
Topics: Animals; Blood Platelets; Cells, Cultured; Eucalyptol; Hemostasis; Humans; Mice; Platelet Activation; Platelet Aggregation; Thrombosis
PubMed: 34685597
DOI: 10.3390/cells10102616 -
Food & Function Jul 2022Many clinical studies have demonstrated the beneficial effects of black tea on cardiovascular diseases. However, the antiplatelet and antithrombotic activities of...
Many clinical studies have demonstrated the beneficial effects of black tea on cardiovascular diseases. However, the antiplatelet and antithrombotic activities of theaflavin (TF-1) remain unknown. In this study, we aimed to investigate the beneficial effects of TF-1 on platelet activation and thrombosis formation both and . Firstly, the antiplatelet activity of TF-1 was analyzed using platelets isolated from human blood aggregometry, flow cytometry, the ELISA kit, western blot and fluorescence microscopy. Subsequently, the analysis of the hemostatic state and thrombosis formation was carried out in C57BL/6 mice based on the tail bleeding time and an FeCl-induced arterial thrombus model. The results showed that TF-1 could prominently inhibit platelet aggregation in a dose-dependent manner, and attenuate P-selectin expression, fibrinogen binding, spreading and thromboxane A2 (TxA2) formation. Western blot analysis showed that TF-1 potently inhibited spleen tyrosine kinase (Syk) and Akt (ser473/474) phosphorylation. The data further confirmed the inhibition of platelet activation by TF-1 with a prolonged arterial occlusion time (from 15.0 ± 1.1 minutes to 40.0 ± 5.4 minutes). All the results indicated that TF-1 is a powerful inhibitor of platelet activation and thrombosis formation in C57BL/6 mice, and could be developed as a novel food-based inhibitor of thrombotic disorders.
Topics: Animals; Antioxidants; Biflavonoids; Blood Platelets; Catechin; Humans; Mice; Mice, Inbred C57BL; Platelet Activation; Platelet Aggregation; Thrombosis
PubMed: 35815842
DOI: 10.1039/d2fo00152g -
Nutrients Jun 2020Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic...
Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic antiplatelet agents by blunting platelet activation receptors via its antioxidant phenomenon. However, there is limited information on the anti-platelet activity of grain-derived polyphenols. The aim of the study is to evaluate the effects of sorghum extract (Shawaya short black 1 variety), an extract previously characterised for its high antioxidant activity and reduction of oxidative stress-related endothelial dysfunction, on platelet aggregation, platelet activation and PMP release. Whole blood samples collected from 18 healthy volunteers were treated with varying non-cytotoxic concentrations of polyphenol-rich black sorghum extract (BSE). Platelet aggregation study utilised 5 µg/mL collagen to target the GPVI pathway of thrombus formation whereas adenine phosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation assessed by flow cytometry. Procaspase-activating compound 1 (PAC-1) and P-selectin/CD62P were used to evaluate platelet activation- related conformational changes and degranulation respectively. PMPs were isolated from unstimulated platelets and quantified by size distribution and binding to CD42b. BSE treatment significantly reduced both collagen-induced platelet aggregation and circulatory PMP release at 40 µg/mL ( 0.001) when compared to control. However, there was no significant impact of BSE on ADP-induced activation-dependent conformational change and degranulation of platelets. Results of this study suggest that phenolic rich BSE may confer cardio-protection by modulating specific signalling pathways involved in platelet activation and PMP release.
Topics: Antioxidants; Blood Platelets; Cell-Derived Microparticles; Flow Cytometry; Humans; Oxidative Stress; Plant Extracts; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Polyphenols; Sorghum
PubMed: 32545505
DOI: 10.3390/nu12061760 -
International Journal of Molecular... Jul 2020Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and... (Review)
Review
Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and in platelet metabolism. Indeed, several signaling pathways have been demonstrated to induce ROS production by NAPDH oxidase (NOX) and mitochondria, upon platelet activation. Platelet-derived ROS, in turn, boost further ROS production and consequent platelet activation, adhesion and recruitment in an auto-amplifying loop. This vicious circle results in a platelet procoagulant phenotype and apoptosis, both accounting for the high thrombotic risk in oxidative stress-related diseases. This review sought to elucidate molecular mechanisms underlying ROS production upon platelet activation and the effects of an altered redox balance on platelet function, focusing on the main advances that have been made in platelet redox biology. Furthermore, given the increasing interest in this field, we also describe the up-to-date methods for detecting platelets, ROS and the platelet bioenergetic profile, which have been proposed as potential disease biomarkers.
Topics: Animals; Apoptosis; Biomarkers; Blood Platelets; Humans; Mitochondria; NADPH Oxidases; Oxidation-Reduction; Platelet Activation; Reactive Oxygen Species; Signal Transduction
PubMed: 32660144
DOI: 10.3390/ijms21144866 -
Frontiers in Immunology 2023
Topics: Humans; COVID-19; Platelet Activation
PubMed: 37818358
DOI: 10.3389/fimmu.2023.1285355 -
Hamostaseologie Feb 2021Platelet activation and aggregation are essential to limit blood loss at sites of vascular injury but may also lead to occlusion of diseased vessels. The platelet... (Review)
Review
Platelet activation and aggregation are essential to limit blood loss at sites of vascular injury but may also lead to occlusion of diseased vessels. The platelet cytoskeleton is a critical component for proper hemostatic function. Platelets change their shape after activation and their contractile machinery mediates thrombus stabilization and clot retraction. In vitro studies have shown that platelets, which come into contact with proteins such as fibrinogen, spread and first form filopodia and then lamellipodia, the latter being plate-like protrusions with branched actin filaments. However, the role of platelet lamellipodia in hemostasis and thrombus formation has been unclear until recently. This short review will briefly summarize the recent findings on the contribution of the actin cytoskeleton and lamellipodial structures to platelet function.
Topics: Actins; Blood Platelets; Humans; Platelet Activation; Thrombosis
PubMed: 33588449
DOI: 10.1055/a-1325-0993 -
Circulation Research Jan 2024
Topics: Mitochondrial Dynamics; Blood Platelets; Megakaryocytes; Hemostasis; Platelet Activation
PubMed: 38236952
DOI: 10.1161/CIRCRESAHA.123.323867 -
Oxidised Low-Density Lipoprotein-Induced Platelet Hyperactivity-Receptors and Signalling Mechanisms.International Journal of Molecular... Aug 2022Dyslipidaemia leads to proatherogenic oxidative lipid stress that promotes vascular inflammation and thrombosis, the pathologies that underpin myocardial infarction,... (Review)
Review
Dyslipidaemia leads to proatherogenic oxidative lipid stress that promotes vascular inflammation and thrombosis, the pathologies that underpin myocardial infarction, stroke, and deep vein thrombosis. These prothrombotic states are driven, at least in part, by platelet hyperactivity, and they are concurrent with the appearancxe of oxidatively modified low-density lipoproteins (LDL) in the circulation. Modified LDL are heterogenous in nature but, in a general sense, constitute a prototype circulating transporter for a plethora of oxidised lipid epitopes that act as danger-associated molecular patterns. It is well-established that oxidatively modified LDL promote platelet activation and arterial thrombosis through a number of constitutively expressed scavenger receptors, which transduce atherogenic lipid stress to a complex array of proactivatory signalling pathways in the platelets. Stimulation of these signalling events underlie the ability of modified LDL to induce platelet activation and blunt platelet inhibitory pathways, as well as promote platelet-mediated coagulation. Accumulating evidence from patients at risk of arterial thrombosis and experimental animal models of disease suggest that oxidised LDL represents a tangible link between the dyslipidaemic environment and increased platelet activation. The aim of this review is to summarise recent advances in our understanding of the pro-thrombotic signalling events induced in platelets by modified LDL ligation, describe the contribution of individual platelet scavenger receptors, and highlight potential future challenges of targeting these pathways.
Topics: Animals; Blood Coagulation; Blood Platelets; Dyslipidemias; Lipoproteins, LDL; Platelet Activation; Thrombosis
PubMed: 36012465
DOI: 10.3390/ijms23169199