Prevalência de alta reatividade plaquetária em pacientes tratados com aspirina encaminhados para angiografia coronária / Prevalence of high platelet reactivity in aspirin-treated patients referred for coronary angiography

FUNDAMENTO: A aspirina (Ácido Acetilsalicílico - AAS) é capaz de reduzir eventos adversos cardiovasculares em pacientes portadores de Doença Arterial Coronariana (DAC) através da inibição da atividade plaquetária. Alguns pacientes com DAC, apesar da terapia com AAS, apresentam Alta Reatividade Plaquetária (ARP), o que determina um maior risco para o desenvolvimento de eventos cardiovasculares. OBJETIVO: O objetivo deste estudo foi determinar a prevalência de ARP em pacientes tratados com AAS e encaminhados para cinecoronariografia, além de avaliar se existe uma possível correlação entre a gravidade da DAC e o desenvolvimento de ARP. MÉTODOS: Estudo de centro único onde foram incluídos 115 pacientes consecutivos, tratados com AAS e portadores de DAC estável. A reatividade plaquetária induzida pelo ADP e colágeno foram avaliadas através da Agregometria de Transmitância Luminosa (ATL). Pacientes com agregação plaquetária maior que 70%, induzida por ambos os reagentes, foram classificados como tendo ARP e, neste grupo, a adesão ao tratamento com AAS foi avaliada através da dosagem dos níveis séricos de salicilato. RESULTADOS: A média de idade foi de 60,9 anos e a dose média de AAS foi de 164,2 mg. Tabagismo e diabetes melito estavam presentes em 28,7% e 31,5% dos pacientes, respectivamente. Foi encontrada ARP em 14 pacientes (13%), entretanto, em sete indivíduos (50%) com ARP observaram-se baixos níveis séricos de salicilato (< 2,0 µg/mL), sugerindo não adesão à terapia medicamentosa. Em 6,5% dos pacientes com ARP identificou-se níveis detectáveis de salicilato sérico, sugerindo uma eficácia reduzida do AAS. A ARP se correlacionou com o número e a gravidade das estenoses coronárias (p = 0,04). CONCLUSÃO: Em uma população de pacientes tratados com AAS e encaminhados para angiografia coronária, a reatividade plaquetária elevada é prevalente (13%), sendo 50% destes pacientes não aderentes à terapia farmacológica e 50% apresentam redução da efetividade da droga.

BACKGROUND: Aspirin (ASA) reduces adverse events in coronary artery disease (CAD) patients by inhibiting platelets. Some CAD patients have high platelet reactivity (HPR) despite ASA therapy and these individuals have increased risk of adverse events. OBJECTIVE: The purpose of this study was to determine the prevalence of HPR in ASA-treated patients referred for coronary angiography and to assess whether the HPR correlates with the severity of CAD. METHODS: This single center investigation enrolled 115 consecutive ASA-treated patients with stable CAD. ADP- and collagen-induced platelet reactivity were evaluated by light transmittance aggregometry (LTA). Patients with greater than 70% ADP- and collagen-induced aggregation were determined to have HPR and, in this group, ASA compliance was assessed by examining blood salicylate levels. Mean age was 60.9 years and average ASA dose was 164.2 mg. RESULTS: Smoking and DM were present in 28.7% and 31.5% respectively. HPR was found in 14 patients (13%) however 7 of the 14 patients (50%) with HPR had low serum salicylate levels (< 2.0 µg/mL) suggesting medication noncompliance. Of the entire cohort, 6.5% of patients had HPR and detectable serum salicylate levels suggesting reduced ASA efficacy. HPR correlated with number and severity of coronary stenosis (p = 0.04). CONCLUSION: In a general population of ASA-treated patients referred for coronary angiography, elevated platelet reactivity is prevalent (13%) with 50% related to noncompliance and 50% related to reduced aspirin efficacy.

Gender differences in the activities of aspirin-esterases in rat tissues

The activities of aspirin (acetylsalicylic acid)-esterases were measured in several tissues (liver, kidney, adrenal glands, brain and serum) from adult male and female Wistar rats. In males, both aspirin-esterase I (assayed at pH 5.5) and II (assayed at pH 7.4) activities were higher in liver homogenates when compared to females (aspirin-esterase I: males 48.9 ñ 4.8 (N = 8) and females 29.3 ñ 4.2 (N = 8) nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 41.4 ñ 4.1 (N = 8) and females 26.1 ñ 4.5 (N = 8) nmol of salicylic acid formed min-1 mg protein-1, P<0.001). In serum, enzyme activity was higher in females than in males (aspirin-esterase I: males 0.85 ñ 0.06 (N = 6) and females 1.18 ñ 0.11 (N = 6) nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 1.03 ñ 0.13 (N = 6) and females 1.34 ñ 0.11 (N = 6) nmol of salicylic acid formed min-1 mg protein-1, P<0.001). In the other tissues assayed, no statistically significant difference between males and females was found. There were no statistically significant differences when the enzymes were assayed in different phases of the estrous cycle in liver and serum. These results show that the differences in aspirin-esterase activity observed between males and females are not due to the estrous cycle. The gender difference obtained in our study may indicate an involvement of gonadal hormones in the control of the hydrolysis of aspirin. This possibility is currently under investigation.

Salicylate level and liver function tests in patients with rheumatic fever and rheumatic heart diseases

This study was carried on 48 cases, their ages ranged from 6 to 12 years. They were classified into 3 groups: 20 patients with rheumatic carditis [group I] and 18 patients with rheumatic arthritis [group II], both groups were in salicylate therapy 100 mg/kg/day. Both groups were matched with 10 apparently healthy children considered as controls. Liver function tests including serum bilirubin, AST, ALT, ALP, GGT, serum albumin and TSP were estimated for all groups and salicylate level for those receiving salicylates. The effect of salicylate therapy in the usual therapeutic dose in rheumatic patients appears to decrease slightly serum proteins and slightly increases liver enzymes AST, ALP and serum bilirubin level. No correlation was found between the dose of salicylate or its duration and the level of hepatic enzymes. There was only a weak negative correlation between the salicylate level and the values of total serum proteins and albumin

Niveles de salicilatos en suero de pacientes con artritis reumatoide juvenil / Serum salicylates levels in patients with juvenile rheumatoid arthritis

Se seleccionaron un total de 20 pacientes con diagnóstico de Artritis Reumatoidea Juvenil, con la finalidad de obtener los niveles séricos de salicilatos, luego de la administración de aspirina, a dosis de 100 mg/kilo/día en dosis fraccionadas cada 8 horas. Los pacientes recibieron la aspirina en forma ambulatoria y luego hospitalizados, obteniéndose muestra de sangre para la determinación de los valores plasmáticos de salicilatos luego de 6 días de terapia consecutiva. Las muestras se cronometraron a la hora 0, a las cuatro y a las ocho horas subsiguientes. Los pacientes ambulatorios mostraron grandes variaciones en las concentraciones séricas de salicilatos, mientras que los que recibieron el fármaco hospitalizados exhibieron niveles terapéuticos aceptables en un 70% de los casos, aunque niveles estables se obtuvieron en el 90% de los mismos. Los niveles de salicilatos obtenidos oscilaron entre 15-18 mg.dl considerados terapéuticos, permanecieron individualmente estables. El 30% que no alcanzaron los niveles terapéuticos eran desnutridos hipoalbuminémicos, aunque todos los pacientes mostraron mejoría clínica excepto uno. La tolerancia a la aspirina fue buena, tanto clínica como de laboratorio. Enfatizamos la mejoría clínica del paciente como parámetro más importante a seguir en el paciente con Artritis Reumatoidea Juvenil, aunque recomendamos la determinación del salicilato total o mejor de su fracción libre en pacientes hipoalbuminémicos o con pH alcalino en la orina