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1.
Rev. cuba. hematol. inmunol. hemoter ; 37(1): e1230, ene.-mar. 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1251721

ABSTRACT

Introducción: Las plaquetas tienen una función clave en la hemostasia primaria a través de cuatro mecanismos fundamentales: adhesión, agregación, secreción y actividad procoagulante, todos controlados genéticamente por más de 50 genes asociados que han sido identificados. Las manifestaciones clínicas en las alteraciones hereditarias de las plaquetas suelen ser variables; aunque estas alteraciones de la coagulación suelen presentarse con una trombocitopenia notoria, también pueden exhibir trombocitopatías, en las cuales la capacidad hemostática de las plaquetas resulta afectada sin variar su número. Por tanto, existen gran variedad de manifestaciones fenotípicas y mutaciones en relación con la función plaquetaria, algunas de las cuales se explicarán más adelante. Objetivo: Realizar revisión práctica sobre mutaciones plaquetarias hereditarias de baja incidencia y destacar la importancia de su conocimiento, correcto diagnóstico, y tratamiento precoz. Métodos: Se realizó revisión literaria en inglés y españolen MEDLINE, EMBASE, Lilacs y ScienceDirect desde mayo 2019 hasta abril 2020, con el uso de combinación de palabras clave y términos MeSH relacionados con trombastenia, genética médica, hemostasis, agregación plaquetaria, trombopoyesis. Se efectuó análisis y resumen de la bibliografía revisada. Conclusión: Entre las alteraciones hereditarias de las plaquetas se pueden encontrar defectos en todos los mecanismos en que participan; sin embargo, la confirmación diagnóstica sigue siendo complicada por el tiempo y el costo que representa lo que ocasiona diagnósticos inadecuados que impactan en el manejo clínico y la evolución(AU)


Introduction: Platelets have a key role in primary hemostasis through four main mechanisms: adhesion, aggregation, secretion and procoagulant activity, all of these controlled by over 50 associated genes that have been identified. Clinical signs of hereditary platelets alterations are usually variable; even though these disorders of hemostasis generally course with a notorious thrombocytopenia, they also might have thrombocytopathies, in which the hemostatic capacity of platelets is affected without altering its number. According to this, there's a great variety of phenotypic manifestations and mutations that affect platelet function, some of these will be explained later on. Objective: To make a practical review of hereditary platelets mutations that have low incidence in population and to highlight the importance of knowing about them, how to diagnose them and early treatment. Methods: A review of literature in both Spanish and English, was done based on MEDLINE, EMBASE, Lilacs and ScienceDirect, during May 2019 and April 2020 using key words and MeSH terms such as thrombasthenia, medical genetics, hemostasis, platelets aggregation, thromopoiesis. Then, an analysis and summary of the reviewed bibliography was carried out. Conclusion: Among the hereditary alterations of platelets, many defects can be found in every mechanism involved; however, diagnostic confirmation is still complicated due to time and cost, causing inaccurate diagnoses that impact on clinic management and evolution(AU)


Subject(s)
Humans , Blood Coagulation , Blood Platelet Disorders/epidemiology , Platelet Aggregation/immunology , Early Diagnosis , Genetics, Medical , Hemostasis/genetics , Blood Platelet Disorders/prevention & control
2.
Rev. cuba. reumatol ; 22(2): e782, mayo.-ago. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1126806

ABSTRACT

Introducción: Las plaquetas contribuyen a la hemostasia y la interrupción heredada o adquirida; en sus procesos bioquímicos pueden alterar la función plaquetaria. Estos trastornos de agregación se han asociado a enfermedades genéticas con afectación del tejido conectivo como el síndrome Ehlers-Danlos, cuyo diagnóstico diferencial con el espectro de hipermovilidad articular resulta difícil clínica y molecularmente. Estas entidades con afectación en las fibras colágenas y diferente repercusión clínica precisan diferenciales en su diagnóstico clínico. Métodos: Se revisaron 353 historias clínicas de pacientes atendidos en el Servicio de Genética del Hospital Pediátrico William Soler desde septiembre del 2009 al 2012, con diagnóstico de hipermovilidad articular por criterios de Beighton y de Ehlers-Danlos según Villefranche (1997). Se incluyó a los pacientes de 5-18 años con resultados documentados del estudio de agregación plaquetaria, valorados por especialistas en hematología. Resultados: Se encontraron trastornos de agregación plaquetaria en 79 de 86 pacientes (92 por ciento). En 7 casos con hipermovilidad de 65 con este diagnóstico (10 por ciento), los resultados fueron negativos. Los 21 con síndrome Ehlers-Danlos tuvieron afectaciones con los fosfolípidos plaquetarios. La hipermovilidad articular estuvo asociada a la combinación difosfato de adenosina (ADP)-epinefrina y el Ehlers-Danlos a la combinación ADP-epinefrina-colágeno-fosfolípidos. Conclusiones: Los pacientes con hipermovilidad articular mostraron asociación a defectos de liberación de gránulos con agonistas como el ADP-epinefrina y los Ehlers-Danlos con la disponibilidad de los fosfolípidos, relacionados con el cambio de forma plaquetaria. Este resultado puede ser una herramienta para conocer el endofenotipo funcional plaquetario como elemento diferencial en los trastornos de la fibra colágena(AU)


Introduction: Platelets contribute to hemostasis and inherited or acquired interruption; in its biochemical processes it can alter platelet function. These aggregation disorders have been associated with genetic diseases with connective tissue involvement such as Ehlers-Danlos syndrome, whose differential diagnosis with the spectrum of joint hypermobility is clinically and molecularly difficult. These entities with involvement of the collagen fibers and different clinical repercussions require differentials in their clinical diagnosis. Methods: 353 medical records of patients attended in the Genetics service of the William Soler Pediatric Hospital from September 2009 to 2012, with a diagnosis of joint hypermobility by Beighton and Ehlers-Danlos criteria according to Villefranche (1997) were reviewed. Patients aged 5-18 years were included with documented results of the platelet aggregation study, assessed by specialists in hematology. Results: Platelet aggregation disorders were found in 79 of 86 patients (92 percent). In 7 cases with hypermobility of 65 with this diagnosis (10 percent), the results were negative. The 21 with Ehlers-Danlos syndrome had affectations with platelet phospholipids. Joint hypermobility was associated with the combination adenosine diphosphate (ADP) -epinephrine and the Ehlers-Danlos with the combination ADP-epinephrine-collagen-phospholipids. Conclusions: Patients with joint hypermobility showed an association to granule release defects with agonists such as ADP-epinephrine and Ehlers-Danlos with the availability of phospholipids, related to platelet shape change. This result can be a tool to know the platelet functional endophenotype as a differential element in collagen fiber disorders(AU)


Subject(s)
Humans , Male , Female , Platelet Aggregation/physiology , Ehlers-Danlos Syndrome/diagnosis , Endophenotypes/analysis , Genetic Diseases, Inborn
3.
Article in English | WPRIM | ID: wpr-880306

ABSTRACT

BACKGROUND@#Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca@*METHODS@#Ca@*RESULTS@#Thapsigargin-induced Ca@*CONCLUSIONS@#The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca


Subject(s)
Antioxidants/administration & dosage , Calcium/physiology , Humans , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Resveratrol/pharmacology , Signal Transduction/drug effects
4.
Article in Chinese | WPRIM | ID: wpr-827188

ABSTRACT

OBJECTIVE@#To investigate the effect of protein kinase A (PKA) activation on aggregation funetion of platelets in vitro.@*METHODS@#The peripheral blood of healthy adults were collected, and the washed platelets were gained from collected peripheral blood. The washed platelets were treated with PKA activator Forskolin, then the platelet aggregation was induced by using Ristocetin, Thrombin, Collagen and ADP respectively, the platelet aggregation level was detected by the platelet aggregator.@*RESULTS@#Compared with the controls, 5 μmol/L forskolin significantly inhibited ADP and collagen-induced platelet aggregation (P<0.001), and showed mild inhibiting effect on Thrombin-induced platelet aggregation (P<0.05). 2.5-10 μmol/L forskolin significantly inhibited ADP and Collagen -induced platelet aggregation (P<0.001); but not showed significantly inhibitory effects on Ristocetin-induced platelet aggregation (P>0.05).@*CONCLUSION@#PKA activation inhibits agonists-induced platelet aggregation.


Subject(s)
Blood Platelets , Cyclic AMP-Dependent Protein Kinases , Humans , Platelet Aggregation , Platelet Aggregation Inhibitors , Ristocetin , Thrombin
5.
Article in Chinese | WPRIM | ID: wpr-878799

ABSTRACT

Genus Veratrum plants contain a diversity of steroidal alkaloids, so far at least 184 steroidal alkaloids attributed to cevanine type(A-1~A-69), veratramine type(B-1~B-21), jervanine type(C-1~C-31), solanidine type(D-1~D-10) and verazine type(E-1~E-53), respectively, have been isolated and identified in the genus Veratrum. Their pharmacological activities mainly focused on decreasing blood pressure, anti-platelet aggregation and anti-thrombosis, anti-inflammatory and analgesic, and antitumor effect. This paper classified and summarized the 184 kind of steroidal alkaloids from the Veratrum plants and their major pharmalogical activities in order to provide the scientific basis for the further development and utilization of active alkaloids.


Subject(s)
Alkaloids/pharmacology , Analgesics , Platelet Aggregation , Steroids/pharmacology , Veratrum
6.
Rev. Fac. Cienc. Méd. Univ. Cuenca ; 38(1): 65-71, 2020. ilus, tab
Article in Spanish | LILACS | ID: biblio-1100688

ABSTRACT

Introducción: la pseudotrombocitopenia inducida por EDTA (ácido etilendiamino tetraacético) es un fenómeno de aglutinación de plaquetas que se presenta in vitro, mediado por anticuerpos anti-plaquetarios de tipo IgG, IgA o IgM dirigidos contra el complejo glucoproteínico IIb/IIIa de la membrana plaquetaria. Caso clínico: presentamos un caso clínico de una paciente de 59 años de edad sometida a recambio valvular aórtico; clínicamente con evolución favorable durante el periodo posquirúrgico, sin embargo, en estudios de control se registra trombocitopenia severa, lo que llevo a cuestionar el uso de anticoagulantes y la necesidad de transfusión de plaquetas. Al realizar estudios complementarios se encontró agregados plaquetarios en el frotis de sangre periférica, posteriormente se realizó recuento seriado de plaquetas y comparación del histograma plaquetario, catalogando el caso como pseudotrombocitopenia. Conclusión: La trombocitopenia por agregados plaquetarios es una condición de baja incidencia (0.07% a 0.1%). Se debe a la agregación de plaquetas in vitro asociada al uso de anticoagulantes, frecuentemente etilendiaminotetraacético (EDTA), en el presente caso también se asoció al uso de citrato de sodio. Este problema no se asocia a sangrado, sin embargo su desconocimiento pudo haber llevado a realizar procedimientos diagnósticos y terapéuticos innecesarios


Introduction: EDTA (ethylenediamine tetraacetic acid) ­induced by pseudothrombocytopenia is a platelet agglutination phenomenon that occurs in vitro, which are mediated by anti-platelet antibodies of the IgG, IgA or IgM type directed against the glycoprotein complex IIb / IIIa of the platelet membrane . Clinical case: This is a clinical case of a 59-yearsold patient undergoing aortic valve replacement, clinically with a favorable evolution during the postoperative period, however, in control studies, severe thrombocytopenia was recorded, which led to questioning the use of anticoagulants and the need for platelet transfusion. When carrying out complementary studies, aggregated platelet were found in the peripheral blood smear, later, a serial platelet count and comparison of the platelet histogram were performed, classifying the case as pseudotrombocytopenia. Conclusion: Thrombocytopenia due to aggregated platelet is a low incidence condition (0.07% to 0.1%). It is due to the aggregation of platelets in vitro associated with the use of anticoagulants [frequently ethylenediamine tetra acetic (EDTA)]; in the present case it was also associated with the use of sodium citrate. This problem is not associated with bleeding; however its lack of knowledge leads to unnecessary diagnostic and therapeutic procedures.


Subject(s)
Humans , Female , Middle Aged , Diagnostic Techniques and Procedures , Antibodies , Anticoagulants/administration & dosage , Immunoglobulin G , Immunoglobulin M , Platelet Aggregation/drug effects
7.
Rev. Assoc. Med. Bras. (1992) ; 65(7): 988-992, July 2019. tab, graf
Article in English | LILACS | ID: biblio-1013006

ABSTRACT

SUMMARY OBJECTIVE The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.


RESUMO OBJETIVO O objetivo deste estudo foi investigar os efeitos da síndrome do baixo triiodotironina (LT3S) na função plaquetária e nos fatores de coagulação em pacientes com síndrome nefrótica (SN). MÉTODOS Pacientes com síndrome nefrótica primária foram divididos em dois grupos, função tireoidiana normal (grupo A) e LT3S (grupo B), com base na presença ou não de LT3S. Indivíduos saudáveis foram selecionados como grupo de controle (grupo C). A função de coagulação do sangue foi analisada em cada grupo. A função de ativação plaquetária (CD62P, CD63) foi determinada por citometria de fluxo. A taxa de agregação plaquetária foi detectada por um método óptico usando adenosina difosfato e ácido araquidônico como indutores. RESULTADOS A proporção de síndrome nefrótica primária com LT3S foi de 23,2% (69/298). Em comparação com o grupo C, o grupo A apresentou níveis mais altos de CD62P e PAgTADP, e o grupo B apresentou maiores CD62P, CD63, PAgTAA e PAgTADP; a diferença teve significância estatística (P < 0,05). Não houve diferença significativa na patologia renal entre o grupo A e o grupo B (X2 = 4,957, P = 0,421). Em comparação com o grupo A, a proteína em urina de 24 horas, CD63, PAgTAA e PAgTADP foram maiores no grupo B, já APTT e Alb foram mais baixos. A diferença apresentou significância estatística (P < 0,05). A análise de regressão logística mostrou uma associação entre LT3S e CD36 (OR: 3,516; 95% IC: 1,742~8,186; P = 0,004) e PAgTAA (OR: 0,442; 95% IC: 1,001~1,251; P = 0,037). CONCLUSÃO Pacientes com síndrome nefrótica estão propensos à síndrome do baixo triiodotironina (LT3S). Pacientes com LT3S podem ter ativação plaquetária anormal e aumento da agregação plaquetária.


Subject(s)
Humans , Male , Female , Adult , Triiodothyronine/blood , Blood Platelets/physiology , Euthyroid Sick Syndromes/physiopathology , Euthyroid Sick Syndromes/blood , Nephrotic Syndrome/physiopathology , Nephrotic Syndrome/blood , Platelet Count , Platelet Function Tests , Reference Values , Triiodothyronine/deficiency , Platelet Activation/drug effects , Platelet Activation/physiology , Platelet Aggregation/drug effects , Platelet Aggregation/physiology , Regression Analysis , Flow Cytometry , Middle Aged , Nephrotic Syndrome/complications
8.
Iatreia ; 32(2): 113-125, ene.-jun. 2019. graf
Article in Spanish | LILACS | ID: biblio-1002145

ABSTRACT

RESUMEN La enfermedad cardiovascular representa, según los datos de la Organización Mundial de la Salud, la principal causa de muerte asociada con factores de riesgo como el tabaquismo, el sedentarismo, la hipertensión, la dislipidemia y la diabetes mellitus. Precisamente, esta última enfermedad es una de las que más se relaciona con la aparición, la progresión y las complicaciones de un evento coronario. La hiperglucemia potencia diferentes vías bioquímicas y celulares como la del sorbitol, el factor nuclear kβ, la formación de productos finales de glicación avanzada, la vía de la proteína cinasa C y el estrés oxidativo, que terminan favoreciendo en el paciente coronario un estado proinflamatorio y procoagulante, que se asocia con un peor pronóstico y agrava la lesión miocárdica; además, inhibe y compite con la acción de los antiagregantes plaquetarios, generando resistencia no solo a estos sino también a la terapia trombolítica. Por lo anterior, se hace necesario generar una actualización del tema, para sensibilizar a la comunidad médica sobre la importancia del control glucémico, sobre todo en pacientes con cardiopatía isquémica, y así mejorar las estrategias de control. Se realizó la búsqueda bibliográfica en PubMed, de una forma estructurada, no sistemática. Se incluyeron artículos publicados en inglés y español, sin restricción por fecha de publicación.


SUMMARY According to data from the World Health Organization, cardiovascular disease is the main cause of death associated with risk factors such as smoking, sedentary lifestyle, hypertension, dyslipidemia and diabetes mellitus. Precisely, this last disease is one of the most related to the appearance, progression, and complications of a coronary event. Hyperglycemia potentiates different biochemical and cellular pathways such as sorbitol, the nuclear factor kβ, the formation of advanced glycation end products, the protein kinase C pathway and oxidative stress, which end up favoring in the coronary patient a proinflammatory state and procoagulant, which is associated with a worse prognosis and aggravates myocardial injury; in addition, it inhibits and competes with the action of platelet antiaggregants, generating resistance not only to these but also to thrombolytic therapy. Therefore, it is necessary to generate an update of the topic, to sensitize the medical community about the importance of glycemic control, especially in patients with ischemic heart disease and thus improve control strategies. The bibliographic search was carried out in PubMed, in a structured, non-systematic way. Articles published in English and Spanish were included, without restriction by publication date.


Subject(s)
Humans , Acute Coronary Syndrome , Hyperglycemia , Platelet Aggregation , Diabetes Mellitus
9.
Article in Chinese | WPRIM | ID: wpr-774509

ABSTRACT

To explore the anti-platelet aggregation and anti-thrombotic mechanisms of Trichosanthis Fructus combined with aspirin based on network pharmacology and the validation of arteriovenous by pass model in rats. The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome(DRAR-CPI),Universal Protein Resource(Uniprot) and the Database for Annotation,Visualization,and Integrated Discovery(DAVID) were used to predict protein targets and analyze biological pathway and signal pathway in the combination of Trichosanthis Fructus with aspirin. The effects of pretreatment with Trichosanthis Fructus pellets,aspirin pellets and their combination on thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) and cyclic adenosine monophosphate(c AMP) in rat thrombotic model were studied. Through the study of network pharmacology,12 components of aspirin and Trichosanthis Fructus,including hydroxygenkwanin,quercetin and adenosine,were found to show the anti-platelet aggregation and anti-thrombosis mechanisms through9 common protein targets,such as SRC,RAC1,MAPK14,MAPK1,AKT1,and 14 common signaling pathways,such as VEGF signaling pathway. After the intervention with Trichosanthis Fructus pellets combined with aspirin pellets,the vascular endothslia growth factor(VEGF) signaling pathway can be activated to inhibit platelet aggregation and improve vascular endothelial function,and show the anti-platelet aggregation and anti-thrombosis mechanisms,which verify the results of the network pharmacology,and explain the anti-platelet aggregation and anti-thrombotic mechanisms of the combination of Trichosanthis Fructus pellets with aspirin pellets.


Subject(s)
6-Ketoprostaglandin F1 alpha , Metabolism , Animals , Aspirin , Pharmacology , Cyclic AMP , Metabolism , Drugs, Chinese Herbal , Pharmacology , Fruit , Chemistry , Platelet Aggregation , Platelet Aggregation Inhibitors , Pharmacology , Rats , Signal Transduction , Thrombosis , Drug Therapy , Thromboxane B2 , Metabolism , Trichosanthes , Chemistry
10.
Article in English | WPRIM | ID: wpr-758889

ABSTRACT

Platelet activation has a major role in hemostasis and thrombosis. Various agonists including adenosine diphosphate (ADP) and thrombin interact with G protein-coupled receptors (GPCRs) which transduce signals through various G proteins. Recent studies have elucidated the role of GPCRs and their corresponding G proteins in the regulation of events involved in platelet activation. However, agonist-induced platelet activation in companion animals has not been elucidated. This study was designed to characterize the platelet response to various agonists in dog platelets. We found that 2-methylthio-ADP-induced dog platelet aggregation was blocked in the presence of either P2Y₁ receptor antagonist MRS2179 or P2Y₁₂ receptor antagonist AR-C69931MX, suggesting that co-activation of both the P2Y₁ and P2Y₁₂ receptors is required for ADP-induced platelet aggregation. Thrombin-induced dog platelet aggregation was inhibited in the presence of either AR-C69931MX or the PKC inhibitor GF109203X, suggesting that thrombin requires secreted ADP to induce platelet aggregation in dog platelets. In addition, thrombin-mediated Akt phosphorylation was inhibited in the presence of GF109203X or AR-C69931MX, indicating that thrombin causes Gi stimulation through the P2Y₁₂ receptor by secreted ADP in dog platelets. Unlike human and murine platelets, protease-activated receptor 4 (PAR4)-activating peptide AYPGKF failed to cause dog platelet aggregation. Moreover, PAR1-activating peptide SFLLRN or co-stimulation of SFLLRN and AYPGKF failed to induce dog platelet aggregation. We conclude that ADP induces platelet aggregation through the P2Y₁ and P2Y₁₂ receptors in dogs. Unlike human and murine platelets, selective activation of the PAR4 receptor may be insufficient to cause platelet aggregation in dog platelets.


Subject(s)
Adenosine Diphosphate , Animals , Blood Platelets , Dogs , GTP-Binding Proteins , Hemostasis , Humans , Pets , Phosphorylation , Platelet Activation , Platelet Aggregation , Receptors, Proteinase-Activated , Thrombin , Thrombosis
11.
Neurointervention ; : 125-130, 2019.
Article in English | WPRIM | ID: wpr-760594

ABSTRACT

PURPOSE: A safe and efficacious antiplatelet drug is needed for patients with clopidogrel resistance who undergo neuroendovascular procedures. Ticagrelor is a new reversibly binding, oral, direct-acting P2Y receptor antagonist with no known resistance. We describe our clinical experience using ticagrelor for neuroendovascular procedures in Indian patients with clopidogrel resistance at the NH Institute of Neurosciences, Narayana Health City, Bangalore. MATERIALS AND METHODS: We retrospectively reviewed our endovascular procedure database for all patients with predefined clopidogrel resistance. Clopidogrel resistance was defined as P2Y12 inhibition <40%. Patients were administered ticagrelor along with aspirin prior to the procedure. RESULTS: Of 127 patients, 32 (25%) were non-responders to clopidogrel (22 [69%] males, 10 [31%] females; median age, 54 years [range, 20–75]). All patients were treated with a 180-mg loading dose of ticagrelor, followed by 90 mg twice daily. Twenty patients (63%) underwent endovascular intervention for intracranial aneurysm, two (6%) for dissecting aneurysms, nine (28%) for stenotic lesions, and one (3%) for carotico-cavernous fistula. No patient experienced any adverse effects related to the use of Ticagrelor in the postoperative period. CONCLUSION: Ticagrelor is an effective alternative to clopidogrel for use in conjunction with aspirin in patients with clopidogrel resistance. None of our patients had adverse effects from ticagrelor. Drug cost, twice-daily dosing, and risk of faster platelet aggregation activation after discontinuation should be taken into consideration prior to its use in such patients.


Subject(s)
Aneurysm, Dissecting , Aspirin , Drug Costs , Endovascular Procedures , Female , Fistula , Humans , Intracranial Aneurysm , Male , Neurosciences , Platelet Aggregation , Postoperative Period , Retrospective Studies , Stents
12.
Article in Chinese | WPRIM | ID: wpr-813084

ABSTRACT

To explore differential expression of long non-coding RNA (lncRNA) in patients with coronary artery disease plus clopidogrel resistance.
 Methods: Patients underwent percutaneous coronary intervention (PCI) and treated with clopidogrel were recruited, and their clinical data and blood samples were collected. Patients were divided into a clopidogrel sensitive group and a clopidogrel resistance group according to platelet aggregation rate. lncRNA microarray and real-time RT-PCR were performed in 5 and 34 patients in each group, respectively.
 Results: lncRNA microarray showed that 11 lncRNAs in peripheral leukocytes were up-regulated and 8 lncRNAs were down-regulated in clopidogrel resistant group. Real-time PCR indicated that two lncRNAs (NONHSAT083775.2 and NONHSAT107804.2) in leukocytes were up-regulated and one lncRNA (NONHSAT133455.2) was down-regulated in the clopidogrel resistant group compared with the clopidogrel sensitive group, consistent with the results of lncRNA microarray.
 Conclusion: Clopidogrel resistance is associated with the up-regulation of lncRNA NONHSAT083775.2 and NONHSAT107804.2 and the down-regulation of NONHSAT133455.2.


Subject(s)
Clopidogrel , Coronary Artery Disease , Genetics , Humans , Percutaneous Coronary Intervention , Platelet Aggregation , Platelet Aggregation Inhibitors , RNA, Long Noncoding
13.
Journal of Experimental Hematology ; (6): 1622-1626, 2019.
Article in Chinese | WPRIM | ID: wpr-775674

ABSTRACT

OBJECTIVE@#To analyze and compare the correlation of platelet aggregation rate measured by platelet analyzer, platelet aggregometer and thromboelastography.@*METHODS@#The performance of platelet analyzer in platelet count and platelet aggregation function was evaluated. The platelet aggregation rate of 55 patients with type 2 diabetes mellitus (T2DM) before and after taking aspirin alone (32 cases) and clopidogrel alone (23 cases) was measured by thromboelastography, platelet aggregometer and platelet analyzer respectively, and the analytical results were compared. The correlation between the results measured by different instruments and equipment were further analyzed and the data were included in the statistical analysis.@*RESULTS@#The precision of platelet analyzer in day and in batch was 1/3 lower than the total error (7%). The contamination rate was 0.30%. The slope of regression equation was 1.02 and R was 0.99 in the linear range of 4.15×10/L to 1379.95×10/L. The coincidence rate of platelet count and platelet reference method was 85%, which met the requirements of industry standards. The platelet aggregation rates of patients with T2DM after clopidogrel or aspirin by using thromboelastography, platelet aggregometer and platelet analyzer respectively was significantly lower than those whom before clopidogrel administration (P<0.01).@*CONCLUSION@#Platelet analyzer can provide reliable, objective and accurate information for clinical detection of platelet count and aggregation function, which is meet the requirements of industry standards, and its results are similar to those of platelet aggregometer and thromboelastography.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Platelet Aggregation , Platelet Aggregation Inhibitors , Platelet Function Tests , Thrombelastography
14.
Clinics ; 74: e1222, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039547

ABSTRACT

OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). CONCLUSION: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Blood Coagulation/physiology , Coronary Artery Disease/blood , Ischemic Attack, Transient/blood , Platelet Aggregation/physiology , Stroke/blood , Fibrinolysis/physiology , Platelet Function Tests , Blood Coagulation Tests , Coronary Artery Disease/physiopathology , Case-Control Studies , Ischemic Attack, Transient/physiopathology , Prospective Studies , Stroke/physiopathology
15.
Braz. j. med. biol. res ; 52(2): e8001, 2019. tab
Article in English | LILACS | ID: biblio-974279

ABSTRACT

There is no definite recommendation for testing platelet aggregation (PA) in acute coronary syndromes (ACS) due to inconclusive evidence on the usefulness of platelet function tests to guide therapy and improve clinical outcomes. The evaluation of PA with multiple electrode impedance platelet aggregometry (MEA) may be useful to manage antiplatelet therapy and possibly influence patient outcome. The primary aim of this study was to measure PA with MEA in Brazilian patients with ACS and evaluate the association between PA and adverse clinical outcomes. Forty-seven consecutive patients admitted with ACS to a Brazilian tertiary-care public hospital were studied and PA was evaluated using MEA. Patients were followed for six months for the occurrence of all-cause death, acute myocardial infarction, or stroke. Suboptimal inhibition of PA was found in 7 patients (14.9%); 5 (10.6%) in response to ASA (acetylsalicylic acid), 2 (5.0%) to clopidogrel, and none to ticagrelor. Inadequate PA inhibition in response to ASA was significantly associated with the composite end point, but there was no significant association for insufficient PA inhibition in response to clopidogrel. This study suggested that the evaluation of PA in ACS using MEA may identify non-responders to ASA. Larger studies are necessary to define, in a public health scenario, the value of MEA in the management of ACS.


Subject(s)
Platelet Aggregation/drug effects , Electric Impedance/therapeutic use , Acute Coronary Syndrome/blood , Platelet Count , Platelet Function Tests , Platelet Aggregation Inhibitors/therapeutic use , Adenosine/therapeutic use , Pilot Projects , Aspirin/therapeutic use , Prospective Studies , Acute Coronary Syndrome/drug therapy , Receptors, Purinergic P2Y12/blood , Tertiary Care Centers , Hospitals, Public
16.
São Paulo; s.n; 2019. 110 p. ilust, tabelas, quadros.
Thesis in Portuguese | LILACS, Inca | ID: biblio-1179935

ABSTRACT

Introdução: O melanoma cutâneo é uma neoplasia maligna dos melanócitos da pele com incidência variável no mundo e o prognóstico é desfavorável nos estágios mais avançados. O desenvolvimento do melanoma está associado ao sistema imunológico e a maior evolução no seu tratamento se deu a partir de medicamentos baseados no estímulo da resposta imune contra o tumor. Objetivo: Avaliar a expressão de citocinas e quimiocinas, dos agregados de plaquetas-leucócitos e de mediadores solúveis sCD40L e sCD62P no sangue de pacientes com melanoma cutâneo. Métodos: Foi realizado um estudo transversal em pacientes com melanoma cutâneo admitidos para tratamento cirúrgico no Hospital de Câncer de Pernambuco (HCP), entre os anos de 2015 e 2018. Foram incluídos 51 pacientes (média de 57,6 anos) com diagnóstico de melanoma cutâneo, e como grupo controle, 30 indivíduos saudáveis (média de 56,7 anos). As coletas de sangue foram realizadas antes da ressecção do melanoma. A determinação dos níveis de citocinas IL6, IL10, TNF, IL1 e IL12p70 e das quimiocinas CXCL10 (IP10), CCL2 (MCP-1), CXCL9 (MIG), CCL5 (RANTES) e CXCL8 (IL8), sCD40L e sCD62P, e agregados plaquetas-leucócitos foi realizada por citometria de fluxo. Foram realizadas análises entre os grupos de pacientes e controles, e pelos parâmetros como tipo histológico, estadio, espessura de Breslow e presença de metástases linfonodais. O teste de Mann-Whitney foi utilizado para comparação entre dois grupos, e de Kruskal-Wallis para as análises entre três ou mais grupos. Foi considerado significativo p<0,05. Resultados: Não houve detecção de IL1 e IL12 no sangue dos pacientes e controles. Verificou-se níveis elevados das citocinas IL10 e diminuídos de TNF nos pacientes comparados ao grupo controle, (p<0,0001). A IL6 esteve aumentada nos pacientes com estadio II em relação ao III (p=0,017) e em pacientes com linfonodos negativos (p<0,0001). Foram encontrados níveis reduzidos da quimiocina CCL5 (p=0,009) nos pacientes quando comparados ao grupo controle. O percentual de agregação plaquetária em linfócitos, monócitos e neutrófilos também foi elevado nos pacientes comparado ao grupo controle (p<0,0001, p=0,009 e p<0,0001 respectivamente). Foram encontrados níveis elevados de agregados plaquetas-monócitos nos pacientes com linfonodos positivos (p=0,008). Os níveis solúveis sCD40L e sCD62P foram elevados nos pacientes comparados aos controles (p=0,03 e p=0,006, respectivamente). Conclusão: Os dados obtidos das análises realizadas mostram que os pacientes com melanoma cutâneo apresentam um perfil imunossupressor com a participação de plaquetas e monócitos/macrófagos que favorecem a progressão tumoral


Cutaneous melanoma is a malignancy originated from the skin melanocytes, with a variable incidence worldwide and a poor prognosis in advanced stages. Melanoma growth is closely associated with the immune system and the most important treatment advances resulted from stimulation of immune response against the tumor. Objective: To evaluate the expression of cytokines and chemokines, platelet-leukocyte aggregates and soluble mediators sCD40L and sCD62P in the blood of patients with cutaneous melanoma. Methods: A cross-sectional study was performed in cutaneous melanoma patients admitted for surgical treatment at the Hospital de Câncer de Pernambuco (HCP) between 2015 and 2018. Fifty-one patients (mean age 57.6 years) with a diagnosis of melanoma were included, and 30 healthy individuals (mean age 56.7 years) were chosen as the control group. The blood samples were taken before resection of the melanoma. The determination of cytokines IL6, IL10, TNFα, IL1ß and IL12p70 and chemokines CXCL10 (IP10), CCL2 (MCP-1), CXCL9 (MIG), CCL5 (RANTES) and CXCL8 (IL8), sCD40L and sCD62P, and platelet-leukocyte aggregate was performed by flow cytometry. Analysis were performed between patient and control groups, and by parameters such as histological type, stage, Breslow thickness, and presence of lymph node metastases. Mann-Whitney test was used for comparison between the two groups, and Kruskal-Wallis test for analysis between three or more groups. It was considered significant p <0.05. Results: There was no detection of IL1ß and IL12 in the blood of patients and controls. Elevated levels of IL10 and decreased TNFα cytokines were found in patients compared to the control group (p <0.0001). IL6 was increased in patients with stage II compared to III (p=0.017) and in patients with negative lymph nodes (p <0.0001). Reduced CCL5 chemokine levels (p=0.009) were found in patients compared to the control group. The percentage of platelet aggregation in lymphocytes, monocytes and neutrophils was also high in patients when compared to the control group (p <0.05). High levels of platelet-monocyte aggregates were found in patients with positive lymph nodes (p=0.008). Soluble sCD40L and sCD62P levels were elevated in patients compared to controls (p=0.03 and p=0.006, respectively). Conclusion: The data obtained from the analysis performed show that patients with cutaneous melanoma have an immunosuppressive profile with platelet participation and monocytes/macrophages that favor tumor progression


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Platelet Aggregation , Cytokines , P-Selectin , Chemokines , CD40 Ligand , Melanoma
17.
Article in Chinese | WPRIM | ID: wpr-773152

ABSTRACT

The thrombus is a deposit that is formed on the surface of the endovascular or at the site of repair,and known as the main complication of cardiovascular disease and the cause of death. At the same time,thrombus is mainly treated by the following three ways: anticoagulation,anti-platelet aggregation and thrombolysis. In this study,the chemical constituents of seven traditional Chinese medicines in the Xixian Tongshuan Preparation were collected to construct a component database. Subsequently,the pharmacophore were used to screen out the component database,and molecular docking was used to screen out the results of pharmacophore for explaining the material basis and mechanism that Xixian Tongshuan Preparation exerts anti-thrombotic activity by inhibiting platelet aggregation. First of all,P2 Y12,GPⅡb/Ⅲa and PAR1 were selected as study vectors,the optimal models of inhibitors were obtained respectively through verification and evaluation of the pharmacophore models. Afterwards,the component database was screened out by the optimal pharmacophore models of PAR1,P2 Y12 and GP Ⅱ b/Ⅲ a,and the molecular docking method was used to further refine the screening results. The screening results indicated that the anti-platelet aggregation effect of Xixian Tongshuan Preparation was correlated with the inhibition of P2 Y12,PAR1 and GPⅡb/Ⅲa expressions with saffower yellower,hirudin and candidin and notoginseng triterpenes,folinic acid,respectively. The material basis and mechanism of anti-platelet aggregation of Xixian Tongshuan Preparation provided a theoretical basis for the clinical use of the preparation and the lead compounds for the development of anti-platelet aggregation drugs.


Subject(s)
Databases, Pharmaceutical , Drugs, Chinese Herbal , Pharmacology , Humans , Molecular Docking Simulation , Platelet Aggregation , Platelet Aggregation Inhibitors , Pharmacology , Thrombosis
18.
Rev. colomb. obstet. ginecol ; 69(2): 132-139, Apr.-June 2018. graf
Article in Spanish | LILACS | ID: biblio-960085

ABSTRACT

RESUMEN Objetivo: describir el diagnóstico y manejo de la hemorragia subaracnoidea secundaria a un aneurisma arterial cerebral accidentado en la primera mitad del embarazo. Materiales y métodos: se presenta el caso de una mujer de 26 años en su segundo embarazo, sin abortos previos y con una cesárea anterior, que fue atendida en un centro de referencia de atención materno perinatal ubicado en Quito, Ecuador, por diagnóstico de hemorragia subaracnoidea durante la decimoséptima semana de gestación. En la panangiografía cerebral se observó un aneurisma cerebral de cuello ancho en la arteria temporal anterior con sangrado. Resultados: se realizó un tratamiento con prótesis endovascular y microespirales, con control de la hemorragia. Posteriormente, la paciente requirió doble antiagregación plaquetaria con clopidogrel y ácido acetilsalicílico que se mantuvo hasta una semana antes del parto. A la paciente se le realizó una cesárea electiva en la que nació un niño sano de 37,2 semanas. Conclusión: el tratamiento endovascular con la colocación de microespirales, asociado al uso de antiagregantes plaquetarios, es una alternativa por considerar en gestantes en la primera mitad del embarazo. Se requieren más estudios clínicos para establecer conductas terapéuticas bien fundamentadas en el manejo de estos casos.


ABSTRACT Objective: To describe the diagnosis and management of a case of subarachnoid haemorrhage secondary to arterial cerebral aneurysm during the first half of gestation. Materials and methods: A 26-year-old woman during a second pregnancy, with no prior miscarriages, and one previous cesarean section seen at a maternal and perinatal care referral centre located in Quito, Ecuador, with a diagnosis of subarachnoid haemorrhage at seventeen weeks of pregnancy. Cerebral pan-angiography showed a wide-neck cerebral aneurysm of the anterior temporal artery with bleeding. Results: Treatment was performed using endovascular stenting and coiling. Later, the patient required dual anti-platelet therapy with clopidogrel and acetylsalicylic acid, maintained up to a week before delivery. Elective cesarean section was performed and the patient was delivered of a healthy baby at 37.2 weeks of gestation. Conclusion: Endovascular treatment with the use of micro-coils, associated with anti-platelet aggregation therapy is an option to consider in pregnant women during the first half of gestation. Further clinical studies are needed in order to identify more fundamental therapeutic approaches for the management of these cases.


Subject(s)
Female , Pregnancy , Subarachnoid Hemorrhage , Pregnancy , Intracranial Arteriovenous Malformations , Platelet Aggregation , Aneurysm
19.
Rev. cuba. hematol. inmunol. hemoter ; 34(2): 153-158, abr.-jun. 2018.
Article in Spanish | LILACS, CUMED | ID: biblio-1042889

ABSTRACT

Durante el embarazo, la hemostasia materna se caracteriza por ser un estado protrombótico en el cual se producen cambios en el sistema hemostático. La adaptación del sistema hemostático materno al embarazo predispone a la madre a un riesgo incrementado de evento trombótico y la presencia de trombofilias genéticas o adquiridas concomitantes aumenta el riesgo de trombosis asociada al embarazo. La tendencia actual en la terapéutica es administrar bajas dosis de aspirina como profilaxis de eventos trombóticos desde el momento de la concepción, hasta el inicio del tercer trimestre, donde se administra heparina de bajo peso molecular para evitar sangrados en el momento del parto. La evaluación de estos fármacos reviste gran importancia en el seguimiento de estas pacientes por el laboratorio, para definir conductas terapéuticas, por lo que este estudio demuestra que el dímero D y la agregación plaquetaria espontánea, constituyen procedimientos experimentales eficaces para evaluar la terapia antiagregante y anticoagulante en embarazadas con tendencias trombóticas. Se pudo comprobar un aumento en los niveles de dímero D de las gestantes y en algunos casos su valor se duplicó en el segundo y tercer trimestre, e incluso en el puerperio; sin embargo, con la conducta terapéutica seguida no se observaron aumentos por encima de 3 µg/mL y la agregación plaquetaria por encima del 40 % permitió definir la interrupción del embarazo. Finalmente, es bueno destacar que con el uso de estas herramientas útiles en el seguimiento de gestantes con trombofilias, se ha logrado introducir a la sociedad 61 neonatos que gozan de excelente salud.


During pregnancy the maternal hemostasis is characterized as a prothrombotic state in which changes in the hemostatic system. The adaptation of the maternal hemostatic system to pregnancy predisposes the mother to an increased risk of thrombotic event and the presence of concomitant genetic or acquired thrombophilia increases the risk of thrombosis associated with pregnancy. The current trend in therapy is to administer low-dose aspirin as prophylaxis for thrombotic events from the moment of conception until the beginning of the third quarter, low molecular weight heparin is administered to prevent bleeding at the time of delivery. The evaluation of these drugs is of great importance in monitoring these patients to define therapeutic conducts, so this study aimed to show that the D-dimer and spontaneous platelet aggregation, are methodologies for assessing the effectiveness of antiplatelet and anticoagulant therapy in pregnant with thrombotic tendencies. He could see an increase in D-dimer levels of pregnant women and in some cases their value doubled in the second and third quarter, and even in the postpartum period, but with the therapeutic behavior followed no increase was observed above 3 µg/mL and platelet aggregation above 40 % allowed to define abortion. Finally note that we have been introduced to society 61 infants who are in excellent health with the use of these useful tools in monitoring pregnant women with thrombophilias.


Subject(s)
Humans , Female , Pregnancy , Platelet Aggregation , Postpartum Period , Aftercare , Anticoagulants
20.
Rev. colomb. cardiol ; 25(2): 154-161, mar.-abr. 2018. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-959966

ABSTRACT

Resumen El síndrome de la plaqueta pegajosa en un trastorno cualitativo plaquetario en el que bajas concentraciones de epinefrina y adenosina difosfato producen hiperagregabilidad plaquetaria considerable. Se ha especulado mucho sobre la etiología de este trastorno sin que sean claros sus mecanismos fisiopatológicos. Desde el punto de vista clínico, se asocia a trombosis arteriales y venosas recurrentes en pacientes jóvenes, pérdidas gestacionales, otras complicaciones obstétricas y cefalea recurrente.En la literatura se ha descrito su presentación familiar, lo que hace sospechar su comportamiento hereditario autosómico dominante; también se ha reportado un fenotipo adquirido de la enfermedad en algunas poblaciones especiales como pacientes con enfermedad renal crónica en terapia de reemplazo renal o posterior al trasplante renal y en pacientes con cuadros inflamatorios o inmunosupresión. Se expone el caso de una paciente con antecedente de cefalea de difícil manejo, síndrome hipertensivo asociado al embarazo y mortinato, con síndrome del nodo enfermo y disautonomía manejadas con implantación de marcapasos definitivo bicameral con sensor CLS, que desarrolló trombosis de la vena subclavia, asociada al electrodo de marcapasos, recurrente a pesar de anticoagulación con warfarina y rivaroxabán e incluso a pesar de antiagregación con ácido acetilsalicílico, con posterior diagnóstico de síndrome de la plaqueta pegajosa.


Abstract Sticky platelet syndrome is a qualitative platelet disorder in which low concentrations of adrenaline and adenosine diphosphate produce considerable platelet hyperaggregability. There has been much speculation on the origin of this disorder as its pathophysiological mechanisms of action are not yet clear. From a clinical point of view, it is associated with recurrent arterial and venous thrombosis in young patients, miscarriages, other obstetric complications and recurrent headaches.Its familial presentation has been described in the literature, suspecting that it is of a dominant autosomal hereditary nature. An acquired phenotype of the disease has also been reported in some particular patients, such as patients with chronic kidney disease on renal replacement therapy or after a kidney transplant, as well as in patients with inflammatory processes or immunosuppression. The case is presented of a patient with a history of difficult to manage headaches, a hypertensive syndrome associated with the pregnancy, and a foetal death. She also had sick sinus node syndrome and dysautonomia managed with a definitive dual-chamber pacemaker with a CLS sensor. There was then a thrombosis in the subclavian vein associated with the pacemaker electrode, being recurrent despite anticoagulation with warfarin and rivaroxaban, and even despite anti-aggregation treatment with acetyl salicylic acid. She was subsequently diagnosed with sticky platelet syndrome.


Subject(s)
Epinephrine , Adenosine , Platelet Aggregation , Venous Thrombosis , Thrombosis , Biological Clocks , Electrodes
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