Eficacia en el control de la anticoagulación de los diferentes fármacos antagonistas de la vitamina K disponibles en Chile

Background: Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen. Aim: To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile. To contrast the overall anticoagulant control efficacy between acenocoumarol and warfarin. Material and Methods: The results of 69333 outpatient oral anticoagulation controls were analyzed. Patient were separated in groups according to the drug that they used. Subsequently, the proportions of controls outside the range for each of acenocoumarol and warfarin bioequivalent drugs were compared. Acenocoumarol non-bioequivalent drugs were also compared with the reference drug. Acenocoumarol was compared with warfarin. Results: Acenocoumarol bioequivalent drugs and the reference drug had a similar proportion of controls outside the range (Odds ratios (OR) 0.812; 0.969; 0.974 and 0.963). Non-bioequivalent drugs had a higher proportion than the reference drug (OR 1.561 and 2.037). Both warfarin brands have a similar proportion of controls outside of the range (OR 1.050). Acenocoumarol compared to warfarin had a significant higher proportion of controls outside the range (OR 1.191). Conclusions: The pharmacological presentation of vitamin K antagonists could influence anticoagulant control. Therefore, it is not prudent to switch these presentations frequently.

Niveles de fosfolipasa A2 asociada a lipoproteína en sujetos sin enfermedad coronaria con riesgo cardiovascular variable / Association of lipoprotein-associated phospholipase activity A2 with cardiovascular risk factors

Background:Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker involved in atherosclerosis and directly associated with cardiovascular events. Aim: To determine Lp-PLA2 levels in asymptomatic subjects with differing cardiovascular risk. Material and Methods: We studied 152 subjects aged 46 ± 11 years (69 women). We recorded traditional cardiovascular risk factors, creatinine, ultrasensitive C-reactive protein, fibrinogen, fasting lipids, blood sugar and activity levels of Lp-PLA2. Cardiovascular risk was classified according to the number of risk factors of each subject (0,1-2 or ≥ 3 risk factors). Besides, we calculated global Framingham risk score. Results: The average Framingham score of participants was 6%. Twenty percent of participants had no risk factors, 46% had 1 or 2 and 34% had ≥ 3. Mean Lp-PLA2 levels were 185 ± 48 nmol/ml/min (201 ± 49 in men and 166 ± 38 in women). Lp-PLA2 correlated significantly (p < 0,05 for all) with non-HDL cholesterol, LDL, HDL, creatinine, waist circumference, body mass index and Framingham risk score. There was no correlation with blood sugar, C-reactive protein, fibrinogen or smoking status. Lp-PLA2 levels were significantly higher according to the number of risk factors: 0 factors: 163 ± 43, 1-2 factors: 185 ± 45 and ≥ 3 factors: 201 ± 47 nmol/ml/min, respectively. Linear regression analysis showed that the best predictor of Lp-PLA2 was non-HDL cholesterol (β= 0,74; p < 0,0001). Conclusions: Lp-PLA2 activity increased along with the number of cardiovascular risk factors and was correlated mainly with non -HDL cholesterol.

Prevalencia de síndrome de Gilbert y sus determinantes genéticas en población chilena / Prevalence of Gilbert syndrome and its genetic determinants in Chile

Background: In Europeans the TATA box TA7 repeat promoter variant in the UGT1A1 gene (UGT1A1*28) is the major determinant of bilirubin levels. Aim: To study the prevalence of Gilbert Syndrome (GS) and its genetic determinants in Chile. Material and Methods: Three different studies were conducted. The prevalence of GS in Chile was assessed in 991 subjects with normal liver tests (ALT and GGT) from the 2nd National Health Survey. We defined GS as a total bilirubin (TB) between 1.4-5mg/dL. The second study assessed the genotype prevalence of SNP rs6742078 (in LD with UGT1A1*28) and rs4149056 in 500 DNA samples of non-related Hispanics. Finally, a case-control study was designed to assess the phenotype-genotype correlation. UGT1A1*28 and rs4149056 variants were determined by direct sequencing and allelic discrimination assays (TaqMan), respectively. Results: Prevalence of GS in the general Chilean population was 2.6% (4.5% in males and 0.5% in female). No correlation with age, educational level or home location was found. Genotypes for UGT1A1*28 (TA6/6 50.5%, TA6/7 37.8%, TA7/7 11.7%) and rs4149056 (TT 74.1%, CT 22.8%, and CC 3.1%) variants were similar to Europeans. In the case-control study, most patients with GS were homozygotes for UGT1A1*28 (TA7/7, 74%). Of note, 44% of patients with intermediate TB levels were also TA7/7, compared to 7% in normal subjects. SLCO1B1 genotype was not correlated with TB levels. Conclusions: While the prevalence of GS was lower in Chile compared to Europeans (~5%), the prevalence of UGT1A1*28 homozygotes was similar (~12%). In Chilean Hispanics, the UGT1A1*28 variant explain 75% of GS phenotype.

Insulinemia e índice HOMA en niños y adolescentes chilenos / Normal plasma insulin and HOMA values among chilean children and adolescents

Background: Plasma insulin and HOMA (homeostasis model assessment) index, used to determine insulin resistance, do not have local standard values for children and adolescents in Chile. Aim: To establish the normal reference intervals for insulin and HOMA in children and adolescents aged 10-15 years, according to sex and puberal maturation. Material and Methods: A cross-sectional study of 2,153 children and adolescents from Puente Alto County was performed, during 2009 and 2010. Anthropometry and self-report of puberal maturation were assessed. Fasting glucose (hexoquinase) and insulin blood levels (chemiluminiscence), were determined and HOMA index was calculated. Percentile distributions of these variables were calculated. Results: The reference group included only subjects with normal body mass index and fasting blood glucose (n = 1,192). Girls had higher insulin and HOMA values than boys (12.5 ± 6.0 and 9.1 ± 4.9 μϋ/mL (p < 0.01) and 2.7 ± 1.4 and 2.1 ± 1,1 (p < 0.01), respectively). Subjects with Tanner I and IIpuberal stages had lower insulin and HOMA mean values than subjects with Tanner III and IV (9.0 ± 4.3 and 12.5 ± 6.2μϋ/ml (p < 0.01) and2.0 ± 1 and2.8 ± 1.4 (p < 0.01), respectively). Conclusions: The 90th percentile of insulin and HOMA distributions according to sex and maturation, was selected as the upper cut-off point to identify individuals with insulin resistance. HOMA cutoff point for Tanner I and II boys was 3.2, for Tanner I and II girls was 4.1, for Tanner III and IV boys was 4.2 and for Tanner III and IV girls was 5.0.

Análisis de las inversiones del intrón 1 y 22 y secuenciación del gen F8 para el diagnóstico genético-molecular de hemofilia A en Chile / Introns 1 and 22 inversions and F8 gene sequencing for molecular diagnosis of hemophilia A in Chile

Background: Hemophilia A is an inherited disorder caused by alterations in factor VIII gene (F8) located on the X-chromosome, the intron 22 inversion being the most common mutation. The rest are predominantly point mutations distributed along this large gene of 26 exons. Aim: To implement a molecular diagnostic test to detect mutations in the F8 gene in Chilean patients with Hemophilia A. Material and Methods: To validate the testing methods, we analyzed samples with intron 22 and intron 1 inversion, and with point mutations previously studied, as well as one subject without Hemophilia. We also studied unrelated Chilean patients with Hemophilia A and their female relatives for carrier testing. Intron 22 and intron 1 inversions were studied by long distance polymerase chain reaction (PCR) and point mutations by sequencing the coding and promoter regions of the F8 gene. Results: The results obtained in all samples used for validation were concordant with those obtained previously. In the Chilean patients, the intron 22 inversion and point mutations previously described were observed. In 6 out of 9 patients with mild Hemophilia A we found the same mutation (Arg2159Cys) in exon 23, which has been described as prevalent in mild Hemophilia A. Conclusions: The analysis of intron 22 and intron 1 inversions, as well as of point mutations in the F8 gene will help us to confirm the diagnosis in patients with severe, moderate and mild Hemophilia A, and also it will allow us to perform carrier testing and to provide better genetic counseling.

Identificación y caracterización del adulto mayor saludable / A novel method for targeting and characterizing healthy older people

Background: There is no established definition of healthy aging in clinical practice, although it is a World Health Organization goal. Aim: To develop a clinical protocol to identify healthy older people living in the community and study their clinical, laboratory and functional characteristics. Material and Methods: Healthy people aged 60 years or older, were invited to participate in the study, by newspapers and radio, if they selfperceived as healthy, lived in the community, were functionally independent and had low disease burden. Potential participants were initially screened by telephone, and those who met the inclusion criteria were included. They had a comprehensive geriatric assessment which included clinical, anthropometric, laboratory and functional assessments. Results: Of 384 people who answered the call, 83 subjects aged 60 to 98 years (57 percent women) met the inclusion criteria of healthy older people. Seventy eight percent did not consume any medication, 100 percent were able to perform physical activities that required at least three metabolic equivalents (Mets). Basic laboratory showed that approximately 90 percent of subjects had normal values, using standard benchmarks established for an adult population. Conclusions: The protocol used in this work was able to identify healthy older people with low disease burden and good functionality. It also validated history and comprehensive geriatric assessment as reliable instruments to identify these subjects.

Correlación clínica y de laboratorio en pacientes pediátricos portadores de enfermedad de von Willebrand / Clinical correlation and of laboratory in carrying pediatrics of disease of Von Willebrand

La Enfermedad de von Willebrand (EvW) es una coagulopatía frecuente en la población. La importancia de pesquisar los diferentes subtipos de esta enfermedad tiene relación con las diversas modalidades terapéuticas y la disminución del uso de hemoderivados. El objetivo de este trabajo fue analizar una población de pacientes pediátricos con diagnóstico de EvW, en control en nuestra Unidad y determinar el subtipo de EvW que presentaban, caracterizando a cada grupo en relación a sus antecedentes, severidad de su sintomatología y utilización de hemoderivados. Se encontró mayor frecuencia de pacientes con EvW tipo 1, con sintomatología hemorragípara variable en su frecuencia e intensidad. Se analiza la sobreutilización de hemoderivados en este grupo de pacientes al no conocer con precisión el tipo de EvW.

Síndromes coronarios agudos: utilidad pronóstica de nuevos biomarcadores y eficacia de un score mixto en el pronóstico clínico alejado / Acute coronary syndromes: practical utility of new biomarkers and mix score efficacy in a long term prognosis

Antecedentes: el uso de biomarcadores ha permitido el diagnóstico y estratificación de pacientes con síndromes coronarios agudos (SCA). Los nuevos biomarcadores en esta área deberán aportar información pronóstica para estratificar pacientes de mayor riesgos en quienes enfocar terapias más agresivas. Objetivo: Estudiar la utilidad de nuevos biomarcadores y el uso un score mixto en la evaluación pronóstica alejada, en pacientes con SCA. Método: Prospectivamente se incorporaron al estudio, pacientes con SCA sin elevación del segmento ST, en quienes se determinó al ingreso niveles plasmáticos de Troponina I específica, proteína C reactiva (PCR), P selectina (PS), Lipoproteína (a) (Lp(a)) y VHS. El seguimiento clínico se extendió por el plazo de un año tras el evento índice. El score mixto fue confeccionado en base a la distribución porcentual de cada biomarcador. Se definieron como endpoints clínicos, mortalidad y nuevos eventos cardiovasculares adversos (ECVA) compuestos ( muerte, reinfarto, angina y rehospitalización por nuevo SCA. Resultados: estudiamos 70 pacientes, con edad promedio de 63 años, 77 por ciento hombres, 21 por ciento diabéticos y 63 por ciento hipertensos. El diagnóstico final fue angina inestable en 71 por ciento e infarto sin elevación del ST en 29 por ciento. El seguimiento clínico se completó en 100 por ciento de los casos. Los valores promedios de los distintos marcadores fueron: Trop I 3,8±7 ng/ml, PCR 25±43 mg/dl, PS 48±28, LPa 16±16 y VHS 23±27. De la serie analizada 17 por ciento tuvo nuevos ECVA y la mortalidad fue de 5,8 por ciento. Los valores de PCR mostraron una asociación significativa con EVCA (p=0,004) y mortalidad (p<0,001). Los valores de Lp(a) también mostraron una asociación con EVCA (P=0,009)pero no con mortalidad (p=0,53). Los valores del score mixto mostraron una fuerte asociación con EVCA y mortalidad (p=0,001). Conclusión: la incorporación de nuevos biomarcadores en la evaluación de pacientes con SCA, puede permitir una mejor estratificación y un mejor uso de las terapias en pacientes de alto riesgo.

Transudado o exudado? observaciones al proceso diagnóstico en derrames pleurales / Transudate or exudate? observations on the diagnostic process of pleural effusions

Los criterios de Light han tenido bajo rendimiento en manos de otros investigadores quienes han propuesto diversos indicadores. El mejor ha sido el uso combinado de colesterol y LDH pleurales: un colesterol sobre 45 mg/dl o una LDH sobre 88 porciento del límite superior normal del suero, identifican a los exudados con una sensibilidad de 99 porciento y una especificidad de 98 porciento exigiendo solo 2 mediciones en líquido pleural. Además, la tríada de Light se ha aplicado ampliamente sin la debida consideración a las diferencias de métodos de medición de LDH de los diferentes laboratorios, por lo que su punto de corte absoluto de 200 U/L en líquido pleural no es válido para todos. Con un límite superior normal para el suero (LSNS) de 300 U/L, el corte en 200 representa, para Light, 2/3 de este límite. Para otros laboratorios cuyo LSNS van de 225 a 460 U/L los puntos de cortes correctos deberían variar entre 150 y 307. Los trabajos de investigación e informes de laboratorio deben indicar su LSNS de manera que el punto de corte para LDH pleural se calcule como proporción de éste

Utilidad de la concentración de colesterol en derrames pleurales para diferenciar entre transudados y exudados / Pleural fluid cholesterol concentration permits differentiation between transudates and exudates

El método usual de diferenciación entre transudados y exudados a través de la concentración de proteínas y LDH en líquido pleural y plasma puede conducir a errores hasta en un 30% de los casos. Se ha comunicados recientemente que la concentración de colesterol es significativamente mayor en los exudados por lo cual se decidió estudiar su valor diagnóstico en comparación a las proteínas y LDH. Para ello medimos estos indicadores en 80 muestras de líquido pleural con diagnóstico etiológico único y comprobado. De acuerdo a la etiología 20 fueron transudados y 60 exudados. En los primeros la concentración de colesterol fue de 19,5 ñ 10,5 y en los segundos 83,5 ñ 37,2 mg/dl (p < 0,001). Se ensayó diversos puntos de corte resultando más útil el de 45 mg/dl: sobre este nivel, la sensibilidad para exudados fue de 88% y la especificidad de 100%. Hubo 7 exudados falsos negativos: 2 neoplasias y 5 de 9 empiemas. Los transudados mal calificados por proteínas y/o LDH bien identificados por el nivel de colesterol y los exudados erróneamente calificados por colesterol fueron bien calificados por proteínas y/o LDH. Ningún derrame fue mal calificados por ambos métodos. Concluímos que una concentración de colesterol sobre 45 mg/dl asegura que el derrame es un exudado, pero puede haber falsos negativos en aproximadamente un 12%. Nuestros resultados suguieren que la sola determinación del colesterol podría reemplazar a las 4 determinaciones que exigen las proteínas y LDH en pleura y plasma para la diferenciación inicial de exudados y transudados, pero que si se sospecha empiema debe preferirse el último método