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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(3): 388-392, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32616137

RESUMO

Platelets are non-nuclear blood cells that are widely involved in physiological and pathological processes.Their main role is to participate in hemostasis and thrombosis.Toll-like receptors(TLRs)are innate immune receptors.Platelets express multiple TLRs and can promote thrombosis by recognizing ligand-induced platelet activation and aggregation.This article reviews the relationship between platelets/TLR and thrombosis and the roles of TLRs in the development of thrombotic diseases.


Assuntos
Plaquetas , Trombose , Hemostasia , Humanos , Ativação Plaquetária , Receptores Toll-Like
3.
Elife ; 92020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32393438

RESUMO

Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.


Assuntos
Redes Neurais de Computação , Agregação Plaquetária , Citometria de Fluxo , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Ativação Plaquetária , Trombose/classificação
6.
Cardiovasc Ther ; 2020: 8703627, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32284734

RESUMO

Antiplatelet therapy is the mainstay of treatment and secondary prevention of cardiovascular disease (CVD), including acute coronary syndrome (ACS), transient ischemic attack (TIA) or minor stroke, and peripheral artery disease (PAD). The P2Y12 inhibitors, of which clopidogrel was the first, play an integral role in antiplatelet therapy and therefore in the treatment and secondary prevention of CVD. This review discusses the available evidence concerning antiplatelet therapy in patients with CVD, with a focus on the role of clopidogrel. In combination with aspirin, clopidogrel is often used as part of dual antiplatelet therapy (DAPT) for the secondary prevention of ACS. Although newer, more potent P2Y12 inhibitors (prasugrel and ticagrelor) show a greater reduction in ischemic risk compared with clopidogrel in randomized trials of ACS patients, these newer P2Y12 inhibitors are often associated with an increased risk of bleeding. Deescalation of DAPT by switching from prasugrel or ticagrelor to clopidogrel may be required in some patients with ACS. Furthermore, real-world studies of ACS patients have not confirmed the benefits of the newer P2Y12 inhibitors over clopidogrel. In patients with very high-risk TIA or stroke, short-term DAPT with clopidogrel plus aspirin for 21-28 days, followed by clopidogrel monotherapy for up to 90 days, is recommended. Clopidogrel monotherapy may also be used in patients with symptomatic PAD. In conclusion, there is strong evidence supporting the use of clopidogrel antiplatelet therapy in several clinical settings, which emphasizes the importance of this medication in clinical practice.


Assuntos
Plaquetas/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Clopidogrel/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Plaquetas/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Medição de Risco , Fatores de Risco , Prevenção Secundária , Resultado do Tratamento
7.
Nat Commun ; 11(1): 2057, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345972

RESUMO

Mass spectrometry (MS)-based targeted lipidomics enables the robust quantification of selected lipids under various biological conditions but comprehensive software tools to support such analyses are lacking. Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.


Assuntos
Lipidômica/métodos , Software , Adulto , Plaquetas/metabolismo , Calibragem , Feminino , Humanos , Lipídeos/sangue , Lipídeos/química , Masculino , Ativação Plaquetária , Probabilidade , Reprodutibilidade dos Testes , Transdução de Sinais , Adulto Jovem
8.
Arterioscler Thromb Vasc Biol ; 40(5): 1340-1351, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32131611

RESUMO

OBJECTIVE: Patients with psoriasis have impaired vascular health and increased cardiovascular disease (CVD). Platelets are key players in the pathogenesis of vascular dysfunction in cardiovascular disease and represent therapeutic targets in cardiovascular prevention. The object of this study was to define the platelet phenotype and effector cell properties on vascular health in psoriasis and evaluate whether aspirin modulates the platelet-induced phenotype. Approach and Results: Platelets from psoriasis patients (n=45) exhibited increased platelet activation (relative to age- and gender-matched controls, n=18), which correlated with psoriasis skin severity. Isolated platelets from psoriasis patients demonstrated a 2- to 3-fold (P<0.01) increased adhesion to human aortic endothelial cells and induced proinflammatory transcriptional changes, including upregulation of IL 8 (interleukin 8), IL1ß, and Cox (cyclooxygenase)-2 Platelet RNA sequencing revealed an interferon signature and elevated expression of COX-1, which correlated with psoriasis disease severity (r=0.83, P=0.01). In a randomized trial of patients with psoriasis, 2 weeks of 81 mg low-dose aspirin, a COX-1 inhibitor, reduced serum thromboxane (Tx) B2 and reduced brachial vein endothelial proinflammatory transcript expression >70% compared with the no-treatment group (P<0.01). Improvement in brachial vein endothelial cell inflammation significantly correlated with change in serum TxB2 (r=0.48, P=0.02). CONCLUSIONS: In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation and suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03228017.


Assuntos
Plaquetas/enzimologia , Ciclo-Oxigenase 1/sangue , Células Endoteliais/enzimologia , Ativação Plaquetária , Psoríase/sangue , Adulto , Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 1/genética , Inibidores de Ciclo-Oxigenase/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adesividade Plaquetária , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/enzimologia , Índice de Gravidade de Doença , Transdução de Sinais , Tromboxano B2/sangue , Resultado do Tratamento
9.
Adv Clin Chem ; 95: 219-243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32122524

RESUMO

The main function of blood platelets is to form hemostatic plugs and enable thrombosis. These properties, however, can be greatly influenced by dietary components which may inhibit certain steps of platelet activation, including platelet aggregation. Such inhibition can play a role in the prophylaxis and treatment of cardiovascular diseases associated with blood platelet hyperactivation. In fact, plant and fish oils have been identified and specifically used for this purpose. Numerous in vivo and in vitro experiments have explored the potential use of these oils to inhibit platelet activation as well as their role in reducing oxidative stress and blood pressure, and lowering triglyceride and cholesterol. This chapter presents and compares the anti-platelet effects of fish and plant oils and their constituents, especially fatty acids. Studies on healthy subjects and patients with various cardiovascular diseases are also examined. Findings indicate that both fish and plant oils contain protective components with anti-platelet activity having clearly defined mechanisms of action. Although both are excellent sources of omega fatty acids and vitamins, plant oils contain components with cardioprotective benefit in hypercholesterolemics, i.e., phytosterols. Plant oils may hence play a key role in strategies for preventing and treating cardiovascular diseases associated with platelet hyperactivation. Further studies are clearly needed to determine the precise dose of these components needed for effective prophylaxis and treatment.


Assuntos
Plaquetas/efeitos dos fármacos , Cardiotônicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Óleos Vegetais/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Animais , Humanos
10.
Int J Nanomedicine ; 15: 1759-1770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214809

RESUMO

Background: There have been many recent reports of molecular probes for thrombi but with unsatisfactory in vivo targeting effects, which could be related to the blood flow velocity in vivo. Therefore, it is worth explaining the relationship between the targeting effect and the blood flow velocity. Methods and Materials: In this study, we constructed a platelet-targeting nanoparticle (NP) based on EWVDV for targeting P-selectin combined with the phase transition material perfluorohexane and India ink to achieve the multimodal imaging of thrombi. We studied the targeting effect of the NPs for rabbit blood thrombi under different flow velocities simulating blood flow velocities in vivo. Results: The results show the successful fabrication of NPs with the ability to undergo a phase transition via low-intensity focused ultrasound irradiation to achieve ultrasound imaging and with a high binding affinity for activated platelets. In vitro, low flow velocities (20 cm/s) hardly affected the targeting effect of the NPs, while moderate flow velocities (40 cm/s) reduced the number of NPs that target thrombi by 52.6% comparing to static fluid (0 cm/s). High flow velocities (60 cm/s) greatly reduced the targeting effect of the NPs by 83.5%. Conclusion: These results can serve as a reference for the design of NPs targeting thrombi at different sites and in different blood vessel types according to the blood flow velocity, thereby establishing a foundation for in vivo experiments.


Assuntos
Plaquetas/efeitos dos fármacos , Imagem Multimodal/métodos , Nanopartículas/administração & dosagem , Trombose/diagnóstico por imagem , Animais , Velocidade do Fluxo Sanguíneo , Carbono/química , Fluorcarbonetos/química , Nanopartículas/química , Selectina-P/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Coelhos , Trombose/sangue , Ultrassonografia
11.
Medicine (Baltimore) ; 99(10): e19336, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150071

RESUMO

BACKGROUND: VerifyNow (VN; Accumetrics, San Diego, CA) P2Y12 reaction unit (PRU) has an inverse relation with hemoglobin level (Hb). Chronic kidney disease (CKD) is associated with low response to clopidogrel and low Hb. Our aim is to investigate the relation between PRU and Hb, and to assess whether Hb directly affects PRU or not in patients with CKD undergoing hemodialysis (HD). METHODS: We analyzed the relation between PRU and Hb in 43 HD patients and compared it with a control group of 127 patients with normal renal function. Both groups underwent percutaneous coronary intervention for stable coronary artery disease. We also compared PRU between the 2 groups considering Hb as a confounding factor. RESULTS: In the control group, Hb and PRU showed a significant inverse correlation (correlation coefficient r = -0.340; P < .001), but not in the HD group (correlation coefficient r = -0.099; P = .53). PRU was higher in the HD group than the control group after adjusting for the influence of Hb (299.2 [95% confidence interval: 278.4-316.7] vs 248.7 [95% confidence interval: 227.7-269.0]; P < .001), even after propensity score matching (299.2 [95% confidence interval: 278.4-316.7] vs 241.7 [95% confidence interval: 221.8-262.2]; P < .001). CONCLUSIONS: PRU was higher regardless of lower Hb in CKD on HD patients than normal renal function patients. Therefore, Hb was not crucial factor to decide PRU in CKD on HD patients in this study.


Assuntos
Clopidogrel/farmacologia , Hemoglobinas/análise , Hemoglobinas/fisiologia , Ativação Plaquetária/fisiologia , Idoso , Clopidogrel/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Testes de Função Plaquetária/métodos , Estudos Prospectivos , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
12.
Mol Immunol ; 120: 83-92, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32106023

RESUMO

Pulmonary fibrosis is a progressive chronic inflammatory lung disease whose pathogenesis is complicated. Platelets and neutrophils play important roles in the progression of pulmonary inflammation. We have reported that cangrelor, a non-sepesific GPR17 antagonist, alleviates pulmonary fibrosis partly by inhibiting macrophage inflammation in mice. Cangrelor is also a well-known anti-platelet agent. To test whether cangrelor mitigated pulmonary fibrosis partly through the inhibition of platelets, bleomycin (BLM) was used to induce pulmonary fibrosis in C57BL/6 J mice. We found that cangrelor (10 mg/kg) not only significantly decreased BLM-induced release of inflammatory cytokines (PF4, CD40 L and MPO), but also decreased the increment of platelets, neutrophils and platelet-neutrophil aggregates in the fibrotic lung and in the peripheral blood of BLM-treated mice. In addition, cangrelor decreased the number of CD40 and MPO double positive neutrophils and the expression level of CD40 in BLM-treated mouse lungs. Based on these results we conclude that cangrelor alleviates BLM-induced lung inflammation and pulmonary fibrosis in mice, partly through inhibition of platelet activation, therefore reducing the infiltration of neutrophils due to the adhesion of platelets and neutrophils mediated by CD40 - CD40 L interaction. Cangrelor could be a potential therapeutic medicine for pulmonary fibrosis.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Ativação Plaquetária/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Animais , Bleomicina/toxicidade , Antígenos CD40/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ativação Plaquetária/imunologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/imunologia
13.
Nat Commun ; 11(1): 398, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964886

RESUMO

A prevailing dogma is that inhibition of vascular thrombosis by antagonizing platelet integrin αIIbß3 cannot be achieved without compromising hemostasis, thus causing serious bleeding and increased morbidity and mortality. It is speculated that these adverse outcomes result from drug-induced activating conformational changes in αIIbß3 but direct proof is lacking. Here, we report the structure-guided design of peptide Hr10 and a modified form of the partial agonist drug tirofiban that act as "pure" antagonists of αIIbß3, i.e., they no longer induce the conformational changes in αIIbß3. Both agents inhibit human platelet aggregation but preserve clot retraction. Hr10 and modified tirofiban are as effective as partial agonist drugs in inhibiting vascular thrombosis in humanized mice, but neither causes serious bleeding, establishing a causal link between partial agonism and impaired hemostasis. Pure orthosteric inhibitors of αIIbß3 may thus provide safer alternatives for human therapy, and valuable tools to probe structure-activity relationships in integrins.


Assuntos
Desenho de Fármacos , Hemorragia/tratamento farmacológico , Peptídeos/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Trombose/prevenção & controle , Animais , Coagulação Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Voluntários Saudáveis , Humanos , Células K562 , Masculino , Camundongos , Camundongos Transgênicos , Peptídeos/química , Peptídeos/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/química , Inibidores da Agregação de Plaquetas/uso terapêutico , Testes de Função Plaquetária , Relação Estrutura-Atividade , Tirofibana/química , Tirofibana/uso terapêutico , Fator de von Willebrand/genética
14.
Medicine (Baltimore) ; 99(4): e18683, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977858

RESUMO

Vicagrel is a new antiplatelet pro-drug based on clopidogrel sulfur lactone metabolites. The purpose of the study was to evaluate the safety, tolerability, and pharmacodynamics (PD) of vicagrel in healthy Chinese subjects.This study was designed as a single-center, randomized, double-blind, placebo-controlled, single oral ascending dose study. Fifty nine subjects were assigned to 6 vicagrel dose cohorts (5, 10, 20, 40, 60, and 75 mg), and 8 subjects were assigned to 75 mg clopidogrel. Within each vicagrel dose cohort, the 10 subjects (9 in the 75 mg cohort) were randomized 4:1 to receive vicagrel or placebo. Platelet function was assessed using VerifyNow P2Y12. ΔP2Y12 reaction units (ΔPRU) and percent inhibition platelet aggregation (%IPA) were used to evaluate the PD of vicagrel.Although the number of adverse events (AEs) increased with vicagrel dose, none were considered serious, suggesting that vicagrel is safe and well-tolerated. The ΔPRU and %IPA patterns suggest that inhibition of ADP-induced platelet aggregation increased in a dose-dependent manner across the 10 to 40 mg dose range. The inhibitory effect was nearly complete at 4 hours (mean %IPA 87.9%-93.0%, mean ΔPRU 206.6-240.0) for doses of 40 to 75 mg of vicagrel. In contrast, for 5 mg vicagrel and 75 mg clopidogrel, there were no measurable effects on platelet aggregation throughout the study.The results suggest that vicagrel at 40 to 75 mg inhibits ADP-induced platelet aggregation, with a fast onset of action and significantly greater potency than clopidogrel. These findings indicate that vicagrel may be a highly effective and well-tolerated antiplatelet agent.


Assuntos
Fenilacetatos/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Tiofenos/farmacologia , Adulto , Clopidogrel/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Fenilacetatos/administração & dosagem , Fenilacetatos/efeitos adversos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Adulto Jovem
15.
Arterioscler Thromb Vasc Biol ; 40(2): 335-349, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31941383

RESUMO

OBJECTIVE: Cardiovascular disease is a major public health problem. Among cardiovascular disease's risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of cardiovascular disease mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipes/hookah has been rising, mainly due to the perception that they are less harmful than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. Approach and Results: We used a waterpipe whole-body exposure protocol that mimics real-life human exposure scenarios and investigated its effects, relative to clean air, on platelet function, hemostasis, and thrombogenesis. We found that waterpipe smoke (WPS)-exposed mice exhibited both shortened thrombus occlusion and bleeding times. Further, our results show that platelets from WPS-exposed mice are hyperactive, with enhanced agonist-induced aggregation, dense and α-granule secretion, αIIbß3 integrin activation, phosphatidylserine expression, and platelet spreading, when compared with clean air-exposed platelets. Finally, at the molecular level, it was found that Akt (protein kinase B) and ERK (extracellular signal-regulated kinases) phosphorylation are enhanced in the WPS and in nicotine-treated platelets. CONCLUSIONS: Our findings demonstrate that WPS exposure directly modulates hemostasis and increases the risk of thrombosis and that this is mediated, in part, via a state of platelet hyperactivity. The negative health impact of WPS/hookah, therefore, should not be underestimated. Moreover, this study should also help in raising public awareness of the toxic effects of waterpipe/hookah.


Assuntos
Plaquetas/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Ativação Plaquetária/fisiologia , Cachimbos de Água , Fumar/efeitos adversos , Trombose/metabolismo , Animais , Plaquetas/metabolismo , Artérias Carótidas/patologia , Cotinina/toxicidade , Modelos Animais de Doenças , Citometria de Fluxo , Seguimentos , Immunoblotting , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nicotina/toxicidade , Contagem de Plaquetas , Fumaça/efeitos adversos , Trombose/induzido quimicamente , Fatores de Tempo
16.
Am J Cardiol ; 125(5): 685-693, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31926634

RESUMO

Elderly patients may have increased platelet reactivity and adverse events after percutaneous coronary intervention. Whether age is an independent predictor of worse outcomes after accounting for platelet reactivity is unknown. We sought to determine the relation between age and platelet reactivity on 2-year outcomes after percutaneous coronary intervention with drug-eluting stents (DES). ADAPT-DES was a prospective observational registry comprising 8,582 DES-treated patients. Patients were categorized with an age cutoff of 75 years. On-clopidogrel platelet reactivity was evaluated with VerifyNow P2Y12 testing. Multivariable Cox proportional hazards regression models were used to describe the relation between increasing age and 2-year clinical outcomes. Patients ≥75 old were more likely to be women and had more cardiovascular risk factors and more extensive coronary artery disease than younger patients. Residual platelet reactivity on-clopidogrel increased slightly with age (adjusted r = 0.05, p <0.0001). Age ≥75 years was associated with greater all-cause mortality (adjusted HR 1.64, 95% CI 1.25 to 2.15, p <0.001), myocardial infarction (adjusted HR 1.33, 95% CI 1.01 to 1.74, p = 0.04) and clinically relevant bleeding (adjusted HR 1.33, 95% CI 1.10 to 1.61 p = 0.003). In contrast, the risk of stent thrombosis was independent of age (adjusted HR 0.83, 95% CI 0.46 to 1.52, and p = 0.55). Considered as a continuous variable, age was directly related to clinically relevant bleeding, cardiac and all-cause mortality, was inversely related to stent thrombosis, and was not related to myocardial infarction. There was no significant interaction between age and on-treatment platelet reactivity for the risk of 2-year clinical outcomes. In conclusion, increasing age had a stronger association with the risk of death and bleeding than of thrombotic events. Despite being associated with older age, higher residual platelet reactivity did not modify the adjusted relative risks of ischemic and bleeding events associated with age.


Assuntos
Síndrome Coronariana Aguda/terapia , Clopidogrel/uso terapêutico , Hemorragia/epidemiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombose/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Causas de Morte , Stents Farmacológicos , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Infarto do Miocárdio/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Adulto Jovem
17.
Blood Coagul Fibrinolysis ; 31(2): 132-139, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31913146

RESUMO

: Mycophenolate mofetil (MMF) raises platelet counts in patients with primary immune thrombocytopenia. However, studies indicate that MMF inhibits collagen-induced platelet aggregation, potentially increasing bleeding risk following MMF therapy. The study evaluates the in-vitro effect of MMF on platelet function. Blood samples (n = 6) from healthy donors were incubated with vehicle, MMF or mycophenolic acid (MPA) at clinically relevant concentrations. Platelet aggregation was measured with flow cytometry and 96-well light transmission aggregometry (LTA). Using flow cytometry, we measured the expression of platelet CD49b, CD42b, CD42a, CD61 and CD41. Platelet activation was measured as the expression of P-selectin and the active form of the GPIIb/IIIa receptor following agonist stimulation. Agonists were: ADP, thrombin receptor-activating peptide, collagen, collagen-related peptide and U46619. The Platelet Function Analyzer-200 was used to measure global platelet function. MMF and MPA did not change platelet aggregation regardless of the agonist used. An exception was a significant, but minor decrease in collagen-induced platelet aggregation in samples with MMF (6 ±â€Š3%, P = 0.02) and MPA (8 ±â€Š4%, P = 0.01) compared with vehicle (22 ±â€Š11%). However, this was not observed using the lesser sensitive LTA method. Compared with vehicle, MPA led to a significantly lower relative disposition of the surface collagen-receptor GPVI (7.8 ±â€Š1.8 versus 8.8 ±â€Š2.1 mean fluorescence intensity, P < 0.001). In all other platelet-related tests, neither MMF nor MPA showed any effect. In conclusion, MMF and MPA only had a minor effect on collagen-induced platelet aggregation, with MPA reducing the relative disposition of surface GPVI receptors.


Assuntos
Plaquetas/efeitos dos fármacos , Ácido Micofenólico/farmacologia , Humanos , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária , Glicoproteínas da Membrana de Plaquetas
18.
Anesth Analg ; 130(3): 654-664, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31633501

RESUMO

Hypercoagulability can occur after severe tissue injury, that is likely related to tissue factor exposure and impaired endothelial release of tissue plasminogen activator (tPA). In contrast, when shock and hypoperfusion occur, activation of the protein C pathway and endothelial tPA release induce a shift from a procoagulant to a hypocoagulable and hyperfibrinolytic state with a high risk of bleeding. Both thrombotic and bleeding phenotypes are associated with increased mortality and are influenced by the extent and severity of tissue injury and degree of hemorrhagic shock. Response to trauma is a complex, dynamic process in which risk can shift from bleeding to thrombosis depending on the injury pattern, hemostatic treatment, individual responses, genetic predisposition, and comorbidities. Based on this body of knowledge, we will review and consider future directions for the management of severely injured trauma patients.


Assuntos
Coagulação Sanguínea , Trombofilia/etiologia , Ferimentos e Lesões/complicações , Animais , Plaquetas/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Fibrinogênio/metabolismo , Fibrinólise , Humanos , Fenótipo , Ativação Plaquetária , Prognóstico , Fatores de Risco , Trombina/metabolismo , Trombofilia/sangue , Trombofilia/fisiopatologia , Trombofilia/terapia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
19.
Altern Ther Health Med ; 26(1): 12-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31634878

RESUMO

Background: Increased platelet activity plays a significant role in the development of arterial thrombosis and cardiovascular disease (CVD). Natural antioxidants including anthocyanin (AC) have gained considerable interest due to their hypothesized antithrombotic potential. Primary Study Objective: Our study aimed to examine the in vitro effect of AC compounds on platelet activation and aggregation. Methods: Fasting blood samples were collected from healthy volunteers (n = 13). A full blood examination was done to exclude any abnormal specimen. Flow cytometer assessed platelet activity by recording platelet surface markers expression of P-selectin (CD62P) and PAC-1. Platelet aggregation studies were performed by stimulating platelets using three different agonists adenosine diphosphate (ADP), collagen and arachidonic acid (AA). Setting: The study was done in the school of Medical Sciences, Griffith University. Participants: Thirteen healthy adult participants were involved for blood collection. Intervention: AC was prepared using hemicellulose capsules sourced from Bilberries and Black Currants. Results: Anthocyanin (50 mg/L) significantly inhibited AA-induced platelet aggregation. Expression of P-selectin was significantly suppressed by 50 mg/L AC as measured by flow cytometer. Conclusions: AC attenuates platelet function by suppressing P-selectin expression and influencing Thromboxane A2 pathway (AA stimulation). These results provide further evidence for the effect of AC and the possible mechanism by which AC reduces platelet aggregation and activation. This study supports future human intervention trials to show that AC may act as a complement to other antiplatelet agents in reducing the risk of thrombosis.


Assuntos
Antocianinas/farmacologia , Plaquetas/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Adulto , Antocianinas/administração & dosagem , Antocianinas/sangue , Plaquetas/metabolismo , Voluntários Saudáveis , Humanos , Inibidores da Agregação de Plaquetas
20.
Cardiovasc Intervent Radiol ; 43(1): 140-146, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31410532

RESUMO

BACKGROUND: Dual antiplatelet therapy is a pre-requisite for flow diverter (FD) implantation. The purpose of this study was to assess the thrombogenicity of the p48 FD, coated with the newly developed phenox Hydrophilic Polymer Coating (p48_HPC, phenox GmbH, Germany) in comparison with uncoated p48 FDs in an in vitro flow model (Chandler Loop). METHODS: p48 and p48_HPC FDs were implanted into silicon tubes filled with whole human blood and incubated at 37 °C under pulsating flow. After 120 min, platelet count was determined in the blood. Platelet activation markers (PAR1) and formation of microparticles were analyzed in a flow cytometer. Fluorescence microscopy of CD42a positive cells and scanning electron microscopy was used to detect adherent platelets on the wire surface. RESULTS: Platelets in contact with the uncoated p48 FDs are significantly more activated than those incubated with p48_HPC (73 ± 9% vs. 65 ± 6%, p < 0.05) and release more microparticles (1.8 ± 0.5 vs. 1.4 ± 0.4, p < 0.05). The platelet count after 120-min circulation in the Chandler Loop was significantly lower for the uncoated p48 compared to the p48_HPC indicating significantly greater adherence of the platelets to the p48 (71 ± 8% vs. 87 ± 5%, p < 0.05). SEM and fluorescent antibody imaging revealed minimal platelet adherence to the surface of the p48_HPC compared to the uncoated p48. CONCLUSION: The pHPC coating significantly reduces thrombogenicity of the p48 FD. This may help to reduce the risk of thromboembolic complications when using these devices. A reduction in antiplatelet therapy may be possible.


Assuntos
Plaquetas/fisiologia , Ativação Plaquetária/fisiologia , Stents , Trombose/prevenção & controle , Citometria de Fluxo , Humanos , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Microscopia de Fluorescência , Polímeros
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