Platelet function tests and Chinese medicines with antiplatelet function:a review / 中国中药杂志

Platelet function tests have been increasingly used to assist in the diagnosis of platelet disorders and prethrombotic state, monitoring of the efficacy of antiplatelet therapies, and personalized treatment. On the basis of light transmission aggregometry, new methods for platelet function test have been developed successively. At present, the research and development of platelet function detector is in its infancy in China. The active constituents of antiplatelet Chinese medicines can be classified into terpenoids, flavonoids, saponins, organic acids, lignans, diketones, volatile oils, and stilbenes. The results of dose-antiplatelet effect relationship of Chinese medicines and the active constituents showed that the effective concentration of the extracts or monomers of Chinese medicines was at micromolar level(μmol·L~(-1)), among which salvianolic acid B and ginkgolide K, ginkgolide B, and ginkgolide A had the strongest antiplatelet effect. These results suggest that the antiplatelet effect of Chinese medicine may be weaker than that of chemical drugs and biological products. Therefore, it is necessary to explore the structure-activity relationship of the active constituents in existing Chinese medicines and further improve their efficacy through structure modification. The antiplatelet effect of Chinese medicines and the constituents involves multiple pathways and multiple targets. These research results provide a reference for clinical application of them. However, there is still a lack of large-scale multi-center clinical trials to confirm the efficacy and safety of them. The regularity of the relationship between the structures of various constituents and their corresponding functions is still unknown and the relevant signal transduction pathways and structure-activity relationship need to be further studied. This paper summarized and analyzed the determination methods of platelet functions and the research results of antiplatelet Chinese medicines, which is of reference value for the research of effective and safe antiplatelet Chinese medicines.

Pruebas de función plaquetaria por el sistema PFA-200 / PFA-200 system for platelet dysfunction analysis

Las pruebas de función plaquetaria realizadas con el analizador PFA-200 (del inglés, Platelet Function Analyzer) han venido reemplazando el tiempo de sangría, una prueba ya obsoleta, de acuerdo con el College of American Pathologists (CAP) y la American Society for Clinical Pathology (ASCP). Este analizador, mediante un sistema que utiliza cartuchos, posee la capacidad de simular in vitro las condiciones hemodinámicas del paciente para el tamizaje rápido, sencillo y automatizado de la disfunción plaquetaria. Las pruebas son de utilidad para evaluar la función plaquetaria en pacientes con alteraciones como enfermedad de von Willebrand y otras trombocitopatías congénitas o adquiridas, y evalúa la disfunción plaquetaria causada por inhibidores de la agregación plaquetaria, como la aspirina. Además, son de gran utilidad para el tamizaje prequirúrgico y en los embarazos de alto riego. Este sistema ofrece con su más reciente prueba, la INNOVANCE® PFA-200 P2Y, la posibilidad de evaluar la respuesta de pacientes que están siendo tratados con antagonistas del receptor plaquetario P2Y12, como son clopidogrel, prasugrel y ticagrelor, determinando el porcentaje de adhesión y agregación plaquetaria, logrando discriminar entre un paciente antiagregado y un paciente resistente al tratamiento

The effect of diclofenac on bleeding, platelet function, and consumption of opioids following cardiac surgery

Abstract Objective: To establish whether the use of diclofenac reduces the administration of opioids and how it affects bleeding and platelet function after the coronary artery bypass grafting (CABG) surgery with use of cardiopulmonary bypass (CPB). Methods: A total of 72 patients undergoing CABG surgery were included in this retrospective randomized study and divided into two groups (34 patients received diclofenac and the control group of 38 patients did not). For postoperative analgesia, both groups were prescribed opioids (piritramide). The primary endpoint was to establish the consumption of opioids. The secondary endpoint was to determine bleeding and the function of platelets 20 hours after the surgery. Results: The consumption of piritramide (diclofenac group 26±8 mg vs. control group 28±8 mg), the blood loss, and the function of platelets did not significantly differ between the groups within 20 hours after surgery. C-reactive protein (CRP) was statistically significantly lower in the diclofenac group than in the control group (33±15 mg/L vs. 46±22 mg/L, respectively, P<0.05). Conclusion: The study concluded that patients administered with diclofenac after the heart surgery did not consume less opioid analgesics and did not exhibit less symptoms linked to the consumption of opioids. Diclofenac in clinically administered doses does not interfere with the function of platelets and does not cause increased bleeding. Lower CRP in the diclofenac group may indicate a reduced inflammatory response after CPB. Therefore, diclofenac could be safe for use in patients undergoing CABG surgery but its value in reducing opioid consumption should be questioned.

High Residual Platelet Reactivity during Aspirin Therapy in Patients with Non-St Segment Elevation Acute Coronary Syndrome: Comparison Between Initial and Late Phases / Alta Atividade Plaquetária Residual em Resposta ao Ácido Acetilsalicílico na Síndrome Coronariana Aguda Sem Supra de ST: Comparação entre as Fases Aguda e Tardia

Abstract Background: High platelet reactivity (HPR) during therapy with acetylsalicylic acid (ASA) is a poor prognostic factor in acute coronary syndromes (ACS). The prevalence of HPR during ACS is greater than that reported in stable diseases. However, it is unclear whether this prevalence of HPR is a transient phenomenon or a characteristic of this high-risk population. Objective: The main objective is to compare the effects of ASA on platelet function in the initial and late phases of ACS in a single population. Secondary objectives are: correlation between the tests between themselves and the relationship between the tests and the variation of the inflammatory markers (C-reactive protein and interleukin-6). Methods: Seventy patients with non-ST segment elevation (NSTE) ACS in use of 100-200 mg of ASA per day for at least 7 days were prospectively studied. Platelet function was assessed in the first 48 hours and subsequently after 3 months using four methods: VerifyNow™ (VFN), whole blood platelet aggregation (WBPA) with arachidonic acid (AA) and collagen as agonists, and platelet function analyzer (PFA). The level of statistical significance considered was < 0.05. Results: According to the more specific methods (WBPA with AA and VFN), the incidence of HPR was significantly higher in the early phase than in the late phase: WBPA with AA: 31% versus 13%, p = 0.015; VFN: 32% versus 16%, p = 0.049. The other methods tested, which were less specific for ASA, did not show significant differences between phases. The correlation between the methods was weak or moderate (r ranging from 0.3 to 0.5, p < 0.05), and there were no significant associations between HPR and inflammatory markers. Conclusion: The prevalence of HPR during AAS therapy, assessed by specific methods for cyclooxygenase 1 (COX-1), is higher during the acute phase than in the late phase of NSTE ACS.

Resumo Fundamento: A alta atividade plaquetária (AAP) durante a terapia com ácido acetilsalicílico (AAS) é fator de mau prognóstico nas síndromes coronarianas agudas (SCA). A prevalência de AAP durante a SCA é maior do que a relatada na doença estável. No entanto, não está claro se esta prevalência de AAP é um fenômeno transitório ou característica dessa população de alto risco. Objetivo: O objetivo principal é comparar, em uma mesma população, os efeitos do AAS sobre a função plaquetária nas fases inicial e tardia da SCA. Os objetivos secundários são: correlação entre os testes entre si e a relação entre os testes e a variação dos marcadores inflamatórios (proteína C reativa e interleucina-6). Métodos: Foram estudados prospectivamente 70 pacientes com SCA sem elevação de ST (SCSST) em uso de 100 a 200 mg de AAS por dia por pelo menos 7 dias. A função plaquetária foi avaliada nas primeiras 48 horas e 3 meses após por quatro métodos: VerifyNow™ (VFN), agregometria de sangue total (AST) com ácido araquidônico (AA) e colágeno como agonistas, e analisador de função plaquetária (PFA). O nível de significância estatístico considerado foi < 0,05. Resultados: A média de idade foi de 65 ±9,7 anos e 54% da população eram do sexo feminino. De acordo com os métodos mais específicos (AST com AA e VFN), a incidência de AAP foi significativamente maior na fase inicial, em relação à tardia: AST com AA 31% versus 13%, p = 0,015; VFN 32% versus 16%, p = 0,049. Os outros métodos testados, menos específicos para o AAS, não mostraram diferenças significativas entre as fases. A correlação entre os métodos foi fraca ou moderada (r variando de 0,3 a 0,5, p < 0,05), e não houve associações significativas entre AAP e marcadores inflamatórios. Conclusão: A prevalência de AAP durante a terapia com AAS, avaliada por métodos específicos para cicloxigenase 1 (COX-1), é maior durante a fase aguda do que na tardia da SCASST.

Low triiodothyronine syndrome is associated with platelet function in patients with nephrotic syndrome

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.

Platelet function, coagulation and fibrinolysis in patients with previous coronary and cerebrovascular ischemic events

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.

Evaluation of platelet activity by multiple electrode impedance aggregometry in acute coronary syndromes: pilot study in a Brazilian tertiary-care public hospital

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.

Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure

As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure

As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

Correlation Analysis of Platelet Aggregation Rate Detected by Platelet Analyzer, Platelet Aggregometer and Thromboelastography / 中国实验血液学杂志

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.

Temporal Variability of Platelet Reactivity in Patients Treated with Clopidogrel or Ticagrelor

BACKGROUND AND OBJECTIVES: The degree of antiplatelet response to P2Y12 inhibitors has been associated with clinical outcomes. The aim of this study was to test the variability of platelet reactivity over time among patients treated with clopidogrel or ticagrelor. METHODS: A single-center cohort of acute coronary syndrome patients that underwent percutaneous coronary intervention (PCI) was analyzed. Platelet reactivity was measured at baseline, 48 hours after PCI, 1 month, and 6 months after clopidogrel (n=79) or ticagrelor (n=93) treatment. High on-treatment platelet reactivity (HPR) was defined as ≥47 U, assessed by multiple electrode platelet aggregometry. RESULTS: Platelet reactivity in the clopidogrel group increased over time, 38.2±21.7 U at 48 hours, 41.4±22.3 U at 1 month, and 44.7±25.5 U at 6 months (p=0.018, 48 hours to 6 months). However, platelet reactivity in the ticagrelor group was not significantly changed, 21.4±12.6 U at 48 hours, 20.0±12.2 U at 1 month, and 22.8±13.8 U at 6 months (p=0.392). A platelet reactivity change over time of more than 20U was found in 67.1% of the patients with clopidogrel group and 34.4% of ticagrelor group (p<0.001). Between 48 hours and 6 months, 43% of patients changed their responder status in the clopidogrel group, and 13% in the ticagrelor group (p<0.001). CONCLUSIONS: Although ticagrelor treatment resulted in less temporal variability of platelet reactivity than clopidogrel treatment in terms of HPR, platelet reactivity varied over time in a significant proportion of patients.

Temporal Variability of Platelet Reactivity Phenotype: Another Barrier to Personalized Antiplatelet Strategy Guided by Platelet Function Testing

No abstract available.

Platelet yield and recovery following the PRGF-U1 protocol in a peruvian population

Objective: to determine the platelet recovery and yield of the PRGF-U1 protocol in a peruvian population. methods: an observational, descriptive and cross-sectional study was conducted with a simple random probability sample of 32 patients who attended the laboratorio Scalab in Trujillo, Peru. a blood sample was taken from each patient in order to obtain the concentration of platelets and before and after the PRGF-U1 protocol, in order to determine platelet recovery and yield. to compare basal platelet concentrations and platelet recovery and yield with gender and age, the chi-square test, student's t-distribution and pearson's correlation coefficient were used considering a significance level of p<0.05. results: platelet yield was less than 2.2 in two patients and greater than or equal to 2.2 in 30 patients; platelet recovery was equal to 0.4 in 30 patients and greater than 0.4 in two patients. a statistically significant relationship (p<0.05) between basal platelet count and age was found when comparing basal platelet count, platelet recovery and platelet yield according to gender and age, but no significant relationship between the other variables (p>0.05). conclusion: the PRGF-U1 protocol presents optimal platelet yield and minimal expected platelet recovery.

Is preoperative clopidogrel resistance a predictor of bleeding and risks in patients undergoing emergency cabg surgery?

Abstract Objective: The aims of this study were to determine whether the detection of preoperative clopidogrel resistance in patients undergoing cardiac surgery while using clopidogrel could play a guiding role in the prediction of postoperative excessive bleeding, transfusion requirements, and risks and to provide clinically significant data. Methods: Two hundred and twenty-two patients [median age: 59.4 (38-83) years; 38 females] undergoing emergency and elective coronary artery bypass graft (CABG) surgeries in our clinic were evaluated prospectively. Patients with multiple systemic diseases, other than diabetes mellitus (DM) and hypertension (HT), were excluded. Patients receiving clopidogrel were also evaluated for clopidogrel resistance and grouped according to the results of this test. Assessments of platelet functions were performed by multiplate impedance aggregometry method and adenosine diphosphate test. Results: The use of postoperative fresh blood replacement and platelet transfusion was higher in patients receiving clopidogrel than in those not receiving it (P=0.001, P=0.018). DM, HT, myocardial infarction, and the number of presentation to the emergency room were significantly higher in patients receiving clopidogrel than in those not receiving it (P<0.05). No significant difference was determined between patients with and without clopidogrel resistance regarding the amount of bleeding during and after surgery, erythrocyte suspension and fresh-frozen plasma transfusion rates, preoperative troponin values, ejection fraction values, and length of hospital stays (P>0.05). Conclusion: We think that resistance studies in patients receiving clopidogrel before cardiac surgery are not efficient to predict bleeding and bleeding-related complications in patients undergoing emergency and elective CABG surgeries.

3D-Morphological Analysis of Inhibitory Effect of Aspirin on Platelet Aggregation / 中国实验血液学杂志

OBJECTIVE@#To develop a new method for evaluating the inhibitory effect of aspirin on platelet by the three-dimensional (3D) morphological parameters.@*METHODS@#The sodium citrate-anticoagulant peripheral blood samples collected from 12 healthy volunteers were divided into 2 groups: group treated with 200 μmol/L acetylsalicylic acid (ASA), and control group. The platelets in the 2 groups were washed and purified. The purified platelets were added into reaction pools modified with type I collagen and induced to activation and aggregation under static condition. The 3D morphology of the formed platelet aggregate was measured by the laser shape microscopic system. Meanwhile, the platelet function was detected by turbidometric light transmittance aggregometry (LTA).@*RESULTS@#This technology could acquire the shape, height and 3D morphology of the platelet aggregates without label, and could quantify their volume parameters. ASA treatment could obviously change the morphology of platelet aggregates. Compared with the parameters of control group, the volume of platelet aggregates in experimental group decreased significantly (t=8.97, P0.05). The receiver-operating characteristic curve(ROC) analysis showed that the platelet aggregate volume as a parameter to identify the ASA inhibition effect had 91.7% sensitivity and 75% specificity when the cut-off value equal to 1395 μm, and its accuracy and sensitivity were both better than those of platelet aggregates rate measured by LTA method.@*CONCLUSION@#The new method developed for evaluating the ASA inhibition of platelet aggregation may provide a complementary strategy for researching and clinically evaluating of ASA anti-platelet aggregation in future.

Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and coagulation function / 医学前沿

Preeclampsia (PE) is a pregnancy-specific, multi-system disorder and the leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. Excessive vasoconstriction and dysregulated coagulation function are closely associated with PE. Heat shock protein 20 (HSP20) is ubiquitously expressed under normal physiological conditions and has important roles in vascular dilatation and suppression of platelet aggregation. However, the role of HSP20 in the pathogenesis of PE remains unclear. In this study, we collected chorionic plate resistance arteries (CPAs) and serum from 118 healthy pregnant women and 80 women with PE and detected the levels of HSP20 and its phosphorylated form. Both HSP20 and phosphorylated HSP20 were downregulated in CPAs from women with PE. Comparison of the vasodilative ability of CPAs from the two groups showed impaired relaxation responses to acetyl choline in preeclamptic vessels. In addition to the reduced HSP20 in serum from women with PE, the platelet distribution width and mean platelet volume were also decreased, and the activated partial thromboplastin time and thromboplastin time were elevated.With regard to the vital roles of HSP20 in mediating vasorelaxation and coagulation function, the decreased HSP20 might contribute to the pathogenesis of PE.

¿Es el volumen medio plaquetario un predictor de mortalidad en sepsis? / Is mean platelet volume a predictor of mortality in sepsis?

Introducción: la sepsis es la respuesta del huésped a una infección sistémica; sus formas severas (sepsis grave y choque séptico) afectan a millones de personas en el mundo, provocando la muerte a uno de cada cuatro pacientes (campaña de sobrevida a la sepsis). Pese a los avances tecnológicos que implican nuevos fármacos, investigación molecular, biomarcadores y estrategias terapéuticas, los logros alcanzados no permiten predecir la severidad del cuadro y anticipar la mortalidad. Objetivo: validar al volumen medio plaquetario (VMP), un valor reportado rutinariamente en el hemograma como predicitor de mortalidad en pacientes sépticos. Material y métodos: se realizó un estudio prospectivo no experimental, en la unidad de terapia intensiva del hospital Pablo Arturo Suárez de Quito en el periodo julio de 2012 hasta octubre de 2014; el universo lo conforman todos los pacientes ingresados con diagnóstico de sepsis que cumplieron los criterios de inclusión. Se consideraron las variables: VMP, contaje leucocitario, sitio de la infección, edad, género y condición al egreso. Resultados: el grupo de estudio se conformó con 87 pacientes; el sitio de infección más frecuente fue a nivel abdominal, seguido de pulmón y vías urinarias. El porcentaje de supervivencia fue 63,2%, dato que coincide con la mortalidad promedio a nivel mundial. Las curva ROC (AUC: 85,4) y la correlación lineal de Pearson (contaje leucocitario­VMP) (r: 0,94), confirman la utilidad del VMP como predictor de mortalidad en casos de sepsis. Conclusión: el volumen medio plaquetario igual o mayor a 8.5 fl predice adecuadamente la mortalidad en pacientes con sepsis. (AU)

Context: Sepsis is the host's response to a systemic infection. Its severe forms (severe sepsis and septic shock) affect millions of people worldwide, leading to death in one in four patients (sepsis survival campaign). Despite technological advances involving new drugs, molecular research, biomarkers and therapeutic strategies, achievements do not allow predicting the severity of the condition and anticipate mortality. Objective: to validate the mean platelet volume (VMP), a value routinely reported in the blood count as a predictor of mortality in septic patients. Materials and methods: a non-experimental prospective study was conducted at the intensive care unit of the Pablo Arturo Suárez Hospital in Quito from July 2012 to October 2014. Universe is made up of all patients admitted with a diagnosis of sepsis who met the inclusion criteria. The following variables were considered: VMP, leukocyte count, site of infection, age, gender and condition at discharge. Results: the study group consisted of 87 patients. The most frequent site of infection was at the abdominal level, followed by lung and urinary tract. The survival rate was 63.2%, which coincides with the average mortality worldwide. The ROC curve (AUC: 85.4) and the linear correlation of Pearson (WBC count-VMP) (r: 0.94) confirm the utility of VMP as a predictor of mortality in sepsis cases. Conclusion: mean platelet volume equal to or greater than 8.5 fl adequately predicts mortality in patients with sepsis. (AU)

Perioperative management and monitoring of antiplatelet agents: a focused review on aspirin and P2Y12 inhibitors / 대한마취과학회지

Platelets play pivotal roles in hemostasis as well as pathological arterial thrombosis. The combination of aspirin and a P2Y₁₂ inhibitor has become the mainstay therapy in the ageing population with cardiovascular conditions, particularly during and after percutaneous coronary intervention. A number of novel P2Y₁₂ inhibitors has become available in the recent years, and they markedly vary in pharmacokinetic and pharmacodynamic properties. Perioperative physicians today face a challenge of preventing hemorrhage due to platelet inhibitors, while minimizing thrombotic risks. There are several point-of-care platelet function tests available in the peri-procedural assessment of residual platelet aggregation. However, these platelet function tests are not standardized in terms of sample processing, agonist type and potency as well as methods of detecting platelet activity. Understanding the differences in pharmacological properties of antiplatelet agents, principles of platelet function tests, and pertinent hemostatic strategies may be useful to anesthesiologists and intensivists who manage perioperative issues associated with antiplatelet agents. The objectives of this review are: 1) to discuss clinical data on aspirin and P2Y12 inhibitors relating to perioperative bleeding, 2) to outline different features of point-of-care platelet function tests, and 3) to discuss therapeutic options for the prevention and treatment of bleeding associated with antiplatelet agents.

Effects of Platelet Number and Platelet Indices on Platelet Reactivity in Patients Treated with Clopidogrel or Ticagrelor / 대한내과학회지

BACKGROUND/AIMS: Platelet counts and characteristics can influence platelet reactivity during antiplatelet therapy. We compared the effects of both platelet count and indices on platelet reactivity between patients who were treated with either clopodogrel or ticagrelor. METHODS: Patients with coronary artery disease who underwent percutaneous coronary intervention were randomly assigned to either the clopidogrel (n = 63) or ticagrelor (n = 65) groups. Platelet count, platelet indices (including mean platelet volume, platelet distribution width, platelet large cell ratio, and immature platelet fraction), and platelet reactivity were measured before intervention, and 48 hours and 30 days post-intervention. High on-treatment platelet reactivity (HPR) was defined as ≥ 47 unit as assessed by multiple electrode platelet aggregometry. RESULTS: Baseline platelet reactivity was similar between the two groups; however, at 48 hours and 30 days, platelet reactivity was significantly lower in the ticagrelor group than in the clopidogrel group. Platelet count, mean platelet volume, platelet distribution width, platelet large cell ratio, and immature platelet fraction were significantly correlated with platelet reactivity in the clopidogrel group; however, these correlations were attenuated in the ticagrelor group. The use of clopodogrel (hazard ratio [HR] 4.1, 95% confidence interval [CI] 1.4–11.9; p = 0.010) and platelet count (HR 9.7, 95% CI 2.9–32.7; p = 0.001) were independent predictors for 30 day HPR. Platelet count was an independent predictor of HPR in the clopidogrel group but not in the ticagrelor group. CONCLUSIONS: Platelet count and indices are significantly correlated with platelet reactivity. However, antiplatelet treatment with ticagrelor could overcome these associations.

Variabilidad de la respuesta plaquetaria a la aspirina / Assessing platelet response to aspirin

Introducción y objetivos: A pesar de que el estudio Antiplatelet Trialists' Collaboration demostró una reducción del 25% de los eventos mayores con el uso de aspirina en enfermos de alto riesgo, un porcentaje de pacientes presentan eventos isquémicos recurrentes. Esto ha llevado a la descripción de la "resistencia a la aspirina" con una tasa muy variable, de 0.4% a 83%. Este estudio evaluó la variabiliad en la función plaquetaria basal, la prevalencia de la resistencia a la aspirina, y la efectividad y reproducibilidad de los estudios de función plaquetaria. Materiales y métodos: Se llevó a cabo un estudio aleatorizado y cruzado de mediciones repetidas, con sujetos saludables de entre 18 y 60 años. Luego de firmar el consentimiento informado, los pacientes fueron distribuidos en forma aleatorizada a recibir aspirina en dosis de 75 mg o 300 mg; fueron evaluados al inicio y luego de cuatro períodos de tres semanas mediante diferentes técnicas: Optical Platelet Aggregation (OPA), PFA-100™, VerifyNow™, y los niveles séricos y urinarios de tromboxano B2 (TXB2). Se obtuvo la aprobación del comité de ética local. El análisis estadístico fue realizado con el programa SPSS17. Resultados: El índice global de resistencia a la aspirina fue variable, entre 2.4% y 63.5% en función de la técnica utilizada. Se demostró una variabilidad interindividual e intraindividual significativa al inicio y con la administración de placebo en las diferentes técnicas. La sensibilidad de los ensayos varió entre 24% (OPA ADP10) y 87.8% (tromboxano sérico), y la especificidad varió entre 81% (PFA-100™) y 97.4% (tromboxano). La selección de "valores de corte" alternativos provocó tasas de prevalencia diferentes de resistencia bioquímica a la aspirina, con un mecanismo de compensación entre la sensibilidad y la especificidad. Conclusiones: La respuesta a la aspirina mostró una marcada variabilidad interensayo, interindividual y temporal. Se requieren varias evaluaciones con diferentes técnicas para diagnosticar en forma confiable la resistencia a la aspirina. La selección de valores discriminativos alternativos debería considerarse al evaluar formalmente esta entidad

Introduction: Despite the 25% reduction in major events with aspirin in high-risk patients reported by the Antiplatelet Trialists' Collaboration, a proportion of patients develop recurrent ischaemic events. This has led to the emergence of 'aspirin resistance' with rates between 0.4% and 83% reported. This study assessed variability in baseline platelet function, prevalence of aspirin resistance, and the performance and reproducibility of platelet function testing methods. Materials and Methods: A repeated-measures randomised crossover study was performed in healthy individuals aged 18-60 years. After informed consent, patients were randomised to aspirin dose (75 mg or 300 mg) and treatment sequence with testing at baseline and after each four 3-week treatment period via Optical Platelet Aggregation (OPA), PFA-100™, VerifyNow™, and serum and urinary thromboxane (TXB2) levels. Local ethical approval was granted. Statistical analysis was performed using SPSS17. Results: The overall rate of aspirin resistance varied from 2.4% to 63.5% depending on the assay used. Significant inter- and intra-individual variability existed at baseline and on placebo testing between assays. Assay sensitivities ranged from 24.0% (OPA ADP10) to 87.8% (serum TXB2), and specificities from 81.0% (PFA-100™) to 97.4% (serum TXB2). Selection of alternative "cut-off" values resulted in differing prevalence rates of biochemical aspirin resistance with a trade-off between sensitivity and specificity. Conclusions: Response to aspirin shows marked inter-assay, inter-individual and temporal variability. Testing on multiple occasions using several assays is necessary to reliably diagnose aspirin resistance. Selection of alternative assay "cut-off" values should be considered when formally assessing aspirin response