Blasting the myth of predictive INR changes related to plasma transfusion: an academic institution's experience

Abstract Introduction Plasma transfusion is a common therapeutic strategy used to lower international normalized ratio (INR) values in the non-emergent setting. However, due to lack of evidence of its efficacy, standardized guidelines for this practice have not been well established. Methods This retrospective observational cohort study analyzed 276 inpatient encounters that involved plasma transfusions focusing on change in INR values from pre- to post-transfusion, with respect to the following predictor variables: vitamin K co-administration, number of plasma units transfused, order indication and body mass index (BMI). Results The overall average change in the INR was 1.35. Patients who received vitamin K showed an average change of 2.51, while patients that did not receive vitamin K demonstrated an average change of 0.70. Increased numbers of plasma units transfused showed benefit up to three-unit orders. Greater decreases in the INR were observed for patients requiring plasma for anticoagulation reversal or active bleeding. There was no significant difference in the change in INR based on the BMI. By multivariate and regression analyses, the stepwise addition of each successive predictor variable demonstrated an increase in the shared variance in the outcome of the post-transfusion INR: the pre-transfusion INR and vitamin K co-administration alone was not significant (p= 0.45); the additional number of plasma units transfused was significant (R² = 0.13, p < 0.001), and; the subsequent additional plasma order indications (R² = 0.19, p < 0.001) and BMI (R² = 0.18, p < 0.001) were increasingly significant. Conclusion Taking into consideration the combination of multiple predictive factors may aid in a more efficient use of plasma products.

Relación entre la presión arterial y el control de la hemorragia post-exodoncia en pacientes bajo tratamiento con warfarina / Relationship between blood pressure and hemorrhage control post exodontia in patients under warfarin treatment

Objetivo: Determinar la relación entre el nivel de pre- sión arterial (PA) y la hemorragia post-exodoncia aplicando medidas de hemostasia local en pacientes bajo tratamiento con warfarina. Materiales y métodos: Este estudio se realizó sobre 30 pacientes (15 hombres y 15 mujeres) bajo tratamiento anti- coagulante oral (TACO) con warfarina. Los pacientes concu- rrían al programa de TACO del Hospital y Centro de Referen- cia de Salud El Pino (HEP y CRS). Se les realizaron una o dos extracciones dentales (n=38) sin suspensión del anticoagulan- te oral a pacientes que tuvieran un coeficiente internacional normalizado (INR) del día menor o igual a 3. Se aplicaron medidas de hemostasia local con gasa compresiva y/o sutura en 30 de las extracciones dentales. Los procedimientos quirúr- gicos fueron llevados a cabo en el Servicio Dental del CRS y HEP. Se registraron las siguientes variables: 1) PA previa a la exodoncia, 2) PA a los 30 minutos, 3) Presencia o ausencia de hemorragia a los 30 minutos post-exodoncia y 4) PA y presen- cia o ausencia de hemorragia a las 24 horas post-exodoncia. Se estudió la relación entre el nivel de PA y la hemorragia post-exodoncia. Resultados: De todos los pacientes evaluados, ninguno presentó hemorragia post-exodoncia en los distintos momen- tos de evaluación, independientemente de cuál fuera su PA. No se encontraron efectos de la variable PA ­considerando valores de PA sistólica (PAS) por debajo de 140 mmHg y de PA diastólica (PAD) menores a 90 mmHg- en relación con la hemorragia post-exodoncia. Conclusión: De acuerdo con los resultados obtenidos en este estudio, la presión arterial con PAS <140 mmHg y PAD <90 mmHg no es un factor que influya en el sangrado post-exodoncia en pacientes bajo tratamiento con warfarina con ≤3 (AU)

Aim: To establish the relationship between blood pres- sure (BP) level and post-exodontic hemorrhage by applying local hemostasis measures in patients under warfarin treat- ment. Materials and methods: This study was conducted in 30 patients (15 men and 15 women) under oral anticoagu- lant (OAC) treatment with warfarin. The patients attended the TACO program of the "Hospital y Centro de Referencia de Salud el Pino (HEP y CRS)". One or two dental extractions (n=38) were performed in the patients that had an INR low- er or equal to 3, without suspending the oral anticoagulant treatment, applying local hemostasis measures with compres- sive gauze and/or suture in 30 of the extractions. The surgical procedure was carried out in the Dental Department of the CRS and HEP. The following variables were registered: 1) BP prior to extraction, 2) BP after 30 minutes, 3) presence or absence of hemorrhage after 30 minutes post-exodontia and 4) BP and presence or absence of hemorrhage 24 hours post-exodontia. The relation between BP level and post-exo- dontic bleeding was studied. Results: Considering all the examined patients, none of them presented post-exodontic hemorrhage at any of the dif- ferent moments of evaluation, regardless of their BP level. No effect of the BP variable ­considering a range of systolic BP SBP) below 140 mmHg and a diastolic BP (DBP) under 90 mmHg- was found in relation to post-exodontic hemorrhage. Conclusion: According to the results obtained in this study, blood pressure with SBP <140 mmHg and DBP <90 mmHg is not an influential factor in post-exodontic bleeding in patients under warfarin treatment with ≤3 (AU)

Estandarización del índice internacional normalizado en pacientes pre-quirúrgicos del Hospital San Juan de Dios de Cuenca / Standarization of the Internacional Normalized Index in pre-surgical patients at Hospital San Juan de Dios of Cuenca / Padronização do Índice Normalizado Internacional em pacientes pré-cirúrgicos do Hospital San Juan de Dios em Cuenca

El índice internacional normalizado (INR, por sus siglas en inglés), es un tipo de cálculo matemático que se basa en las pruebas de tiempo de protrombina. La seguridad y eficacia de la terapia dependen del efecto anticoagulante que reciban dentro del margen terapéutico fijado por el médico en base al estudio de sus tiempos de coagulación, específicamente expresado como el intervalo de INR. Establecer los rangos de referencia del INR aplicado en resultados obtenidos en pacientes del sexo masculino y femenino en edades entre los 18 hasta 60 años de edad en el Hospital San Juan de Dios de Cuenca, durante los meses de enero a junio del año 2021. Los datos fueron recopilados de 699 pacientes que acudieron a consulta externa del Hospital San Juan de Dios de Cuenca del área de hematología, que incluyen valores de tiempo de tromboplastina y su referente INR en base al ISI establecido en el reactivo emitido por el fabricante. Se establecieron los valores normales de INR los cuales varían en referencia al sexo del paciente. Para el sexo masculino valores con límite inferior 0,82 y límite superior 1,16; para el sexo femenino con límite inferior de 0,51 y el límite superior de 1,51. Los valores de INR tienen variaciones de acuerdo al sexo siendo los valores de hombres mas altos en relación al de las mujeres en el rango inferiores, Evidentemente los factores influyentes van en relación del sexo, edad, dieta y sobretodo la genética del paciente.

The International Normalized Ratio (INR) is a type of mathematical calculation based on prothrombin time testing. The safety and efficacy of therapy depend on the anticoagulant effect they receive within the therapeutic range set by the physician based on the study of their clotting times, specifically expressed as the INR range. To establish the reference ranges of the INR applied in results obtained in male and female patients between 18 and 60 years of age at the San Juan de Dios Hospital in Cuenca, during the months of January to June 2021. The data were collected from 699 patients who attended the outpatient clinic of the Hospital San Juan de Dios de Cuenca in the hematology area, including thromboplastin time values and their INR referent based on the ISI established in the reagent issued by the manufacturer. Normal INR values were established, which vary according to the patient's sex. For the male sex values with a lower limit of 0.82 and an upper limit of 1.16; for the female sex with a lower limit of 0.51 and an upper limit of 1.51. The INR values vary according to sex, with the values for men being higher in relation to those for women in the lower range. Evidently, the influencing factors are related to sex, age, diet and above all the patient's genetics.

A Relação Internacional Normalizada (INR) é um tipo de cálculo matemático baseado em testes de tempo de protrombina. A segurança e eficácia da terapia depende do efeito anticoagulante que recebem dentro da faixa terapêutica estabelecida pelo médico com base no estudo de seus tempos de coagulação, expressa especificamente como a faixa INR. Estabelecer as faixas de referência do INR aplicadas em resultados obtidos em pacientes do sexo masculino e feminino com idade entre 18 e 60 anos no Hospital San Juan de Dios em Cuenca, durante os meses de janeiro a junho de 2021. Os dados foram coletados de 699 pacientes que compareceram ao ambulatório do Hospital San Juan de Dios de Cuenca na área de hematologia, incluindo os valores de tempo de tromboplastina e sua referência INR baseada no ISI estabelecido no reagente emitido pelo fabricante. Foram estabelecidos valores normais de INR, que variam de acordo com o sexo do paciente. Para o sexo masculino, com um limite inferior de 0,82 e um limite superior de 1,16; para o sexo feminino, com um limite inferior de 0,51 e um limite superior de 1,51. Os valores de INR variam de acordo com o sexo, sendo os valores para os homens maiores em relação àqueles para as mulheres na faixa inferior. Evidentemente, os fatores de influência estão relacionados ao sexo, idade, dieta e, acima de tudo, à genética do paciente.

Riesgo de sangrado en pacientes anticoagulados con antagonistas de la vitamina K que reciben antibióticos / Risk of bleeding in anticoagulated patients with vitamin K antagonists who receive antibiotics

Lograr un adecuado nivel de anticoagulación con antagonistas orales de la vitamina K suele ser un desafío frecuente en la práctica clínica, dado que su estrecho rango terapéutico suele verse afectado por diversas interacciones farmacológicas,alimentos y condiciones clínicas. A partir de un caso de un paciente anticoagulado que presenta una hemorragia gastro-intestinal posterior a realizar un tratamiento antibiótico, la autora de este artículo revisó la evidencia sobre el riesgo desangrado secundario a la interacción entre este tipo de anticoagulantes y antibióticos orales. Su conclusión tras realizar una búsqueda bibliográfica y seleccionar la mejor evidencia disponible, es que existe un aumento del riesgo relativo desangrado en pacientes anticoagulados que reciben antibióticos, por lo que deberían evitarse aquellos antibióticos con conocido potencial de interacción. Si ello no fuera posible, se recomienda monitorizar el estado de anticoagulación con dosaje de la razón internacional normatizada (RIN) posterior a la introducción del antibiótico. (AU)

Achieving an adequate level of anticoagulation with oral vitamin K antagonists is often a frequent challenge in clinical practice, given that their narrow therapeutic range is often affected by various drug interactions, food, and clinical conditions. Based on a case of an anticoagulated patient who presented gastrointestinal bleeding after antibiotic treatment, the authorof this article reviewed the evidence on the risk of secondary bleeding due to the interaction between this type of anticoagulants and oral antibiotics. Their conclusion, after performing a literature search and selecting the best available evidence, is that there is an increased relative risk of bleeding in anticoagulated patients receiving antibiotics, so antibiotics with known potential for interaction should be avoided. If it weren't possible, it is recommended to monitor the anticoagulation status with International Normalized Ratio (INR) dosing after the introduction of the antibiotic. (AU)

Evolución del grado de control de una cohorte de pacientes anticoagulados de Atención Primaria / Evolution of the degree of control in a cohort of anticoagulated patients in Primary Care

Introducción: Solo el 60 por ciento de los pacientes en tratamiento con antagonistas de la vitamina K (AVK) están controlados. Objetivos: A nalizar una cohorte de pacientes anticoagulados para valorar su grado de control y su evolución a los 2 años, tras una intervención formativa breve. Métodos: Estudio longitudinal, observacional, retrospectivo de 157 anticoagulados con AVK. Se recogieron datos sociodemográficos, comorbilidades, motivo de prescripción del AVK y grado de control basal y tras 2 años de seguimiento. Utilizamos 2 métodos de valoración diferentes: Rosendaal y método directo (porcentaje de INR-Razón Normalizada Internacional- en rango). Asimismo, establecimos correlaciones temporales intramétodo. Resultados: El grado de control pasó del 47,3 por ciento al 53,5 por ciento a los 2 años, según Rosendaal (p= 0,52), y del 39,5 por ciento al 53,5 por ciento según el método directo (p< 0,05). El tiempo en rango terapéutico fue del 63,1 ±19,9 por ciento al inicio y 65 ±19,2 por ciento al final del seguimiento. La correlación entre los 2 controles fue positiva para ambos métodos (Rosendaal: 0,23; método directo: 0,33). El análisis multivariante fue significativo para el sexo masculino y para un objetivo diferente de 2,5-3,5 (odds ratio: 2,22 y 2,73, respectivamente). Conclusiones: El control del INR mejoró a los 2 años de seguimiento tras la actividad formativa. La evolución del grado de control de cada paciente es parcialmente predecible. El peor control se asoció al sexo femenino y al objetivo de INR de 2,5-3,5. El control mejora 2,22 veces en los varones y 2,73 veces en quienes no tienen un INR objetivo de 2,5-3,5(AU)

Introduction: Only 60 percent of patients on treatment with vitamin K antagonists (AVK) are controlled. Objectives: We proposed to analyze a cohort of anticoagulated patients to assess their degree of control and their evolution at 2 years, after a brief training intervention. Methods: Longitudinal, observational, retrospective study of 157 anticoagulated with AVK. Sociodemographic data, comorbidities, reason for VKA prescription and degree of baseline control were collected and after 2 years of follow-up. We use 2 different valuation methods: Rosendaal and direct method (INR percentage -International Normalized Ratio- in range). Likewise, we established intra-method temporal correlations. Results: The degree of control went from 47.3 percent to 53.5 percent at 2 years, according to Rosendaal (p = 0.52), and from 39.5 percent to 53.5 percent according to the direct method (p<0.05). The time in the therapeutic range was 63.1±19.9 percent at the start and 65±19.2 percent at the end of the follow-up. The correlation between the 2 controls was positive for both methods (Rosendaal: 0.23; direct method:0.33). The multivariate analysis was significant for males and for a target other than 2.5-3.5(odds ratio: 2.22 and 2.73, respectively). Conclusions: INR control improved after 2 years of follow-up after training activity. The evolution of the degree of control of each patient is partially predictable. The worst control was associated with female sex and the INR goal of 2.5-3.5. Control improves 2.22 times in males and 2.73 times in those without a target INR of 2.5-3.5(AU)

Tiempo en rango terapéutico en pacientes con fibrilación auricular anticoagulados con warfarina en el Instituto Nacional del Tórax / Time in therapeutic range in patients with atrial fibrillation anticoagulated with warfarin at the Instituto Nacional de Torax

INTRODUCCIÓN: la fibrilación auricular es la arritmia más frecuente, siendo una patología trombogénica, por lo que en la mayoría de los casos es necesaria la anticoagulación. Uno de los agentes más usados es la warfarina y su efecto se determina mediante el INR y el tiempo que el paciente se mantiene en rango terapéutico, denominado Tiempo en Rango Terapéutico. OBJETIVO: determinar el Tiempo en Rango Terapéutico en pacientes con Fibrilación Auricular que acuden a consulta externa de cardiología en el Instituto Nacional del Tórax MATERIALES Y MÉTODOS: se hizo la revisión de expedientes clínicos de pacientes que acudieron a consulta externa de cardiología con fibrilación auricular de 2017 a 2019 y se calculó el TTR mediante el método de Rosendaal y porcentaje de INRs en rango terapéutico RESULTADOS: de 212 pacientes dentro del universo se incluyeron en el estudio 49 pacientes. La edad promedio fue de 67,49 ±12,33 años, con un 63,3% de pacientes de sexo femenino. El TTR calculado por método de Rosendaal fue de 34±25,98% y el TTR calculado por porcentaje de INRs en rango fue de 31,31±24,01%. El porcentaje de pacientes con TTR adecuado (≥70%) fue del 10,2%. CONCLUSIÓN: los pacientes con fibrilación auricular anticoagulados con warfarina que acuden a consulta externa de cardiología del Instituto Nacional del Tórax presentan un nivel inadecuado de Tiempo en rango terapéutico. (AU)

INTRODUCTION: atrial fibrillation is the most frequent arrhythmia, being a thrombogenic pathology, so anticoagulation is necessary in most cases. One of the most used agents is warfarin and its effect is determined by the INR and the time that the patient remains in the therapeutic range, called Time in Therapeutic Range OBJECTIVE: to determine the Time in Therapeutic Range in patients with Atrial Fibrillation who attend outpatient cardiology consultation at the Instituto Nacional del Tórax MATERIALS AND METHODS: the clinical records of patients who attended the outpatient cardiology consultation with atrial fibrillation from 2017 to 2019 were reviewed and the TTR was calculated using the Rosendaal method and percentage of INRs in the therapeutic range RESULTS: of 212 patients within the universe, 49 patients were included in the study. The average age was 67.49 ± 12.33 years, with 63.3% of female patients. The TTR calculated by the Rosendaal method was 34 ± 25.98% and the TTR calculated by percentage of INRs in range was 31.31 ± 24.01%. The percentage of patients with adequate TTR (≥70%) was 10.2%. CONCLUSION: patients with atrial fibrillation anticoagulated with warfarin who attend the outpatient clinic of cardiology of the Instituto Nacional del Tórax present an inadequate level of Time in therapeutic range.(AU)

Atrial Fibrillation and Use of Rivaroxaban: Performance of the Prothrombin Time / INR as a Function of Time After Blood Collection

Abstract Background Traditionally, the most effective therapy in the prevention of stroke in patients with atrial fibrillation (AF) has been oral anticoagulation with vitamin K inhibitors, particularly warfarin, whose disadvantages and adverse effects have led to their replacement by "direct oral anticoagulants", as factor X inhibitor. Objectives This study aimed to conduct a brief approach on atrial fibrillation (AF) and use of Rivaroxaban, and to comparatively evaluate the prothrombin time / International Normalized Ratio (PT/INR) in patients with AF in use of this oral anticoagulant, depending on the time elapsed between the last administration of the drug and the time of blood sample venipuncture. Methods We evaluated 34 patients with AF in use of Rivaroxaban by using PT / INR, distributed into a subgroup with blood collection time ≤ 12 hours (n = 7) and > 12 hours after the last drug intake (n = 27). Mann-Whitney test was used to compare the groups and p < 0.05 was considered significant. Results An analysis as a function of time between the Rivaroxaban intake and blood collection, revealed that PT / INR suffers the greatest effect up to 12 hours after ingestion of the drug, dropping to levels close to normal in subsequent hours before the next dose. Conclusion We concluded that, in contrast to warfarin, the knowledge of the time interval between drug intake and blood collection from patients taking Rivaroxaban is essential to properly interpret a laboratory test to assess hemostasis, particularly PT and its derivatives. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Consenso argentino en gestión efectiva de clínicas de anticoagulación para uso de antagonistas de la vitamina K / Argentine consensus in effective management of anticoagulation clinics for the use of vitamin K antagonists

Resumen El tratamiento de un paciente anticoagulado con antagonistas de la vitamina K (AVK) sigue siendo un desafío, especialmente en regiones donde, por el costo, los dicumarínicos son todavía la alternativa más buscada a la hora de elegir un anticoagulante oral. Las clínicas de anticoagulación han demostrado ser la forma más eficiente y segura de evitar complicaciones trombóticas y hemorrágicas y de mantener al paciente en rango óptimo de tratamiento. Sin embargo, requieren de una adecuada infraestructura y personal capacitado para que funcionen eficientemente. En este consenso argentino se propone una serie de parámetros para la gestión efectiva de una clínica de anticoagulación. El objetivo es lograr una elevada calidad desde el punto de vista clínico-asistencial a través de un laboratorio de hemostasia de excelencia. Los criterios desarrollados en el documento fueron consensuados por un amplio grupo de expertos especialistas en hematología y en bioquímica de todo el país. Estos criterios deben adaptarse a la irregular disponibilidad de recursos de cada centro, pero siempre se los debe tener en cuenta a la hora de indicar el tratamiento anticoagulante con estas drogas. Tener en consideración estas premisas nos permitirá optimizar la atención del enfermo anticoagulado con AVK y de esta forma minimizar las intercurrencias trombóticas y hemorrágicas a las que está expuesto, para así honrar nuestra promesa de no dañar al paciente.

Abstract Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.

Warfarin drug interaction with vitamin K and other foodstuffs / Interacción de la droga warfarina con la vitamina K y otros productos alimenticios

Vitamin K is found in higher concentrations in dark green plant and in vegetable oils. The adequate intake of vitamin K is 90 and 120ug/day for adult elderly men and women, respectively. The main function of vitamin K is to act as an enzymatic cofactor for hepatic prothrombin synthesis, blood coagulation factors, and anticoagulant proteins. Prominent among the many available anticoagulants is warfarin, an antagonist of vitamin K, which exerts its anticoagulant effects by inhibiting the synthesis of vitamin K1 and vitamin KH2. From the beginning of the therapy it is necessary that the patients carry out the monitoring through the prothrombin time and the international normalized ratio. However, it is known that very low intake and/or fluctuations in vitamin K intake are as harmful as high consumption. In addition, other foods can interact with warfarin, despite their content of vitamin K. The aim of this study was to gather information on the drug interaction of warfarin with vitamin K and with dietary supplements and other foods.

La vitamina K se encuentra en concentraciones más altas en plantas de color verde oscuro y en aceites vegetales. La ingesta adecuada de vitamina K es de 90 y 120 ug/día para hombres y mujeres adultos mayores, respectivamente. La función principal de la vitamina K es actuar como un cofactor enzimático para la síntesis de protrombina hepática, factores de coagulación de la sangre y proteínas anticoagulantes. Entre los muchos anticoagulantes disponibles destaca la warfarina, un antagonista de la vitamina K, que ejerce sus efectos anticoagulantes al inhibir la síntesis de la vitamina K1 y la vitamina KH2. Desde el inicio de la terapia, es necesario que los pacientes realicen el monitoreo a través del tiempo de protrombina y la proporción normalizada internacional. Sin embargo, se sabe que una ingesta muy baja y/o fluctuaciones en la ingesta de vitamina K son tan dañinas como un consumo alto. Además, otros alimentos pueden interactuar con la warfarina, a pesar de su contenido de vitamina K. El objetivo de este estudio fue recopilar información sobre la interacción de los medicamentos de la warfarina con la vitamina K y con los suplementos dietéticos y otros alimentos.

Anticoagulation Therapy in Patients with Non-valvular Atrial Fibrillation in a Private Setting in Brazil: A Real-World Study / Terapia de Anticoagulação em Pacientes com Fibrilação Atrial não Valvar em Ambiente de Cuidado de Saúde Privado no Brasil: Um Estudo de Mundo Real

Abstract Background: The safety and effectiveness of warfarin depend on anticoagulation control quality. Observational studies associate poor control with increased morbidity, mortality and healthcare costs. Objectives: To develop a profile of non-valvular atrial fibrillation (NVAF) patients treated with warfarin in a Brazilian private ambulatory and hospital setting, evaluate the quality of anticoagulation control, and its association with clinical and economic outcomes. Methods: This retrospective study, through a private health insurance dataset in Brazil, identified NVAF patients treated with warfarin between 01 MAY 2014 to 30 APRIL 2016, described their anticoagulation management, and quantified disease-related costs. Data on demographics, clinical history, concomitant medication and time in therapeutic range (TTR) of international normalized ratio (INR) values were retrieved. Patients were grouped into TTR quartiles, with good control defined as TTR ≥ 65% (Rosendaal method). Major bleeds and all-cause direct medical costs were calculated and compared between good and poor control subgroups. P-values < 0.05 were considered statistically significant. Results: The analysis included 1220 patients (median follow-up: 1.5 years; IQR: 0.5-2.0). On average, each patient received 0.95 monthly INR measurements (mean INR: 2.60 ± 0.88, with 26.1% of values < 2 and 24.8% > 3), (median TTR: 58%; IQR: 47-68%), (mean TTR: 56.6% ± 18.9%). Only 31% of patients were well-controlled (mean TTR: 78% ± 10%), with 1.6% having major bleeds within median follow-up, and direct medical costs per member per year (PMPY) of R$25,352(± R$ 37,762). Poorly controlled patients (69%) were associated with 3.3 times more major bleeds (5.3% vs. 1.6%; p < 0.01) and 40% higher costs (R$35,384 vs. R$25,352; p < 0.01). Conclusions: More than 60% of the patients were below the desired target and the associated costs were higher.

Resumo Fundamento: A segurança e a eficácia da varfarina dependem da qualidade do controle da anticoagulação. Estudos observacionais associam controle deficiente com aumento de morbidade, mortalidade e custos com saúde. Objetivos: Desenvolver um perfil de pacientes com fibrilação atrial não valvar (FANV) tratados com varfarina em ambiente ambulatorial e hospitalar privado brasileiro, avaliar a qualidade do controle da anticoagulação e sua associação com resultados clínicos e econômicos. Métodos: Este estudo retrospectivo, por meio de um conjunto de dados de seguros privados de saúde no Brasil, identificou pacientes com FANV tratados com varfarina entre 01 de maio de 2014 a 30 de abril de 2016, descreveu seu manejo da anticoagulação e quantificou os custos relacionados à doença. Foram recuperados dados demográficos, histórico clínico, medicação concomitante e tempo na faixa terapêutica (TTR) dos valores da razão normalizada internacional (RNI). Os pacientes foram agrupados em quartis de TTR, com um bom controle sendo definido como TTR ≥65% (método de Rosendaal). Sangramentos maiores e custos médicos diretos por todas as causas foram calculados e comparados entre subgrupos de controle bons e ruins. Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: A análise incluiu 1220 pacientes (mediana de seguimento: 1,5 anos; IIQ: 0,5-2,0). Em média, cada paciente recebeu 0,95 medidas mensais de RNI (RNI média: 2,60 ± 0,88, com 26,1% dos valores < 2 e 24,8% > 3), (mediana de TTR: 58%; IIQ: 47-68%), (TTR médio: 56,6% ± 18,9%). Apenas 31% dos pacientes estavam bem controlados (TTR médio: 78% ± 10%), com 1,6% apresentando grandes sangramentos na mediana do seguimento e custos médicos diretos por membro por ano (PMPY) de R$25.352 (± R$37.762). Pacientes com controle abaixo do ideal (69%) foram associados a 3,3 vezes mais sangramentos graves (5,3% vs. 1,6%; p <0,01) e custos 40% maiores (R$35.384 vs. R$25.352; p < 0,01). Conclusões: Mais de 60% dos pacientes estavam abaixo da meta desejada e os custos associados foram significativamente maiores nesta população.

Culture-Positive Spontaneous Ascitic Infection in Patients with Acute Decompensated Cirrhosis: Multidrug-Resistant Pathogens and Antibiotic Strategies

Impact of Anticoagulation Intensity in Korean Patients with Atrial Fibrillation: Is It Different from Western Population?

BACKGROUND AND OBJECTIVES: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients.METHODS: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death.RESULTS: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6–2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19–0.85), major bleeding (HR, 0.43; 95% CI, 0.23–0.81), primary (HR, 0.50; 95% CI, 0.29–0.84) and secondary (HR, 0.45; 95% CI, 0.28–0.74) net-clinical outcomes, whereas mean INR 2.0–3.0 did not. Simultaneous satisfaction of mean INR 1.6–2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes.CONCLUSIONS: Mean INR 1.6–2.6 was better than mean INR 2.0–3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6–2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0–3.0 and TTR ≥70% in Korean patients with non-valvular AF.

Why do some trauma patients die while others survive? A matched-pair analysis based on data from Trauma Register DGU® / 中华创伤杂志(英文版)

PURPOSE@#The mortality rate for severely injured patients with the injury severity score (ISS) ≥16 has decreased in Germany. There is robust evidence that mortality is influenced not only by the acute trauma itself but also by physical health, age and sex. The aim of this study was to identify other possible influences on the mortality of severely injured patients.@*METHODS@#In a matched-pair analysis of data from Trauma Register DGU®, non-surviving patients from Germany between 2009 and 2014 with an ISS≥16 were compared with surviving matching partners. Matching was performed on the basis of age, sex, physical health, injury pattern, trauma mechanism, conscious state at the scene of the accident based on the Glasgow coma scale, and the presence of shock on arrival at the emergency room.@*RESULTS@#We matched two homogeneous groups, each of which consisted of 657 patients (535 male, average age 37 years). There was no significant difference in the vital parameters at the scene of the accident, the length of the pre-hospital phase, the type of transport (ground or air), pre-hospital fluid management and amounts, ISS, initial care level, the length of the emergency room stay, the care received at night or from on-call personnel during the weekend, the use of abdominal sonographic imaging, the type of X-ray imaging used, and the percentage of patients who developed sepsis. We found a significant difference in the new injury severity score, the frequency of multi-organ failure, hemoglobine at admission, base excess and international normalized ratio in the emergency room, the type of accident (fall or road traffic accident), the pre-hospital intubation rate, reanimation, in-hospital fluid management, the frequency of transfusion, tomography (whole-body computed tomography), and the necessity of emergency intervention.@*CONCLUSION@#Previously postulated factors such as the level of care and the length of the emergency room stay did not appear to have a significant influence in this study. Further studies should be conducted to analyse the identified factors with a view to optimising the treatment of severely injured patients. Our study shows that there are significant factors that can predict or influence the mortality of severely injured patients.

Relação entre parâmetros hemostáticos, evolução clínica e desfecho de pacientes diagnosticados com sepse / Relationship between hemostatic parameters, clinical evolution and outcome of patients diagnosed with sepsis

Sepse é definida como uma resposta inflamatória sistêmica frente a um microrganismo, sendo uma das principais causas de morte em pacientes internados em unidades de terapia intensiva (UTI). Na sepse, a cascata de coagulação é ativada, contribuindo na formação de tromboembolismo venoso localizado e coagulação intravascular disseminada, uma das responsáveis pela síndrome da disfunção orgânica múltipla; além disso, o consumo de plaquetas e de proteínas de coagulação pode resultar em hemorragias graves. Pacientes com sepse internados em UTI têm como principais prestadores de assistência a equipe de enfermagem que pode ter suas atividades organizadas pela Sistematização da Assistência de Enfermagem (SAE). A SAE possibilita perspectivas em relação ao cuidado, guia e normatiza mais precisamente a assistência de enfermagem direcionando a resolução dos problemas dos pacientes, pois mobiliza competências profissionais específicas no cuidado, resultando na qualidade da assistência. Esse estudo objetivou avaliar a relação de dois componentes do sistema hemostático (contagem de plaquetas e International Normalized Ratio - INR) com a gravidade clínica e com o desfecho em pacientes diagnosticados com sepse internados na UTI. Trata-se de um estudo quantitativo, exploratório e correlacional no qual os dados foram coletados de maneira pregressa. O estudo desenvolveu-se num hospital público de cuidados de alta complexidade em nível ambulatorial e hospitalar, por meio da análise de prontuários de pacientes diagnosticados com sepse internados na UTI no período de janeiro a dezembro de 2017. As variáveis relacionadas às características sócio- demográficas, clínicas e o tempo de assistência de enfermagem foram coletadas do prontuário eletrônico dos pacientes utilizando-se formulário específico. Foram incluídos 176 prontuários. Não foram observadas diferenças estatisticamente significantes em relação ao sexo, idade ou raça dos pacientes, contudo, os resultados mostram que pacientes com desfecho óbito apresentaram piores valores dos parâmetros clínicos e laboratoriais, demandaram mais cuidados de enfermagem e apresentaram contagem de plaquetas menor e INR maior do que os pacientes que tiveram alta; além disso, observou-se que a contagem de plaquetas <100.000 mm3 e o INR>1,5 estão associados à maior frequência do desfecho óbito. Foi analisada a capacidade da contagem de plaquetas e do INR para predizerem o óbito por meio de uma curva ROC que indicaram a contagem de plaquetas como um preditor não adequado e o INR um preditor fraco para o desfecho óbito. Assim, este estudo mostrou que os pacientes diagnosticados com sepse que foram a óbito apresentaram maior comprometimento orgânico e demandaram mais cuidados de enfermagem do que aqueles que tiveram como desfecho a alta hospitalar, além disso, a contagem de plaquetas e o INR indicam um comprometimento do sistema hemostático, sinalizando um quadro fibrinolítico. Tanto a contagem de plaquetas quanto o INR foram associados ao óbito, no entanto, não se mostraram bons preditores para tal. O dimensionamento do trabalho de enfermagem utilizando o NAS, a avaliação dos exames laboratoriais e da gravidade através dos SAPS 3, realizados pelo enfermeiro com conhecimento específico, facilita a elaboração e evolução da SAE. Quanto mais dados, mais acurada a análise, levando a modificações do planejamento da assistência de enfermagem

Sepsis is defined as a systemic inflammatory response to a microorganism, being a major cause of death in intensive care unit (ICU) patients. In sepsis, the coagulation cascade is activated, contributing to the formation of localized venous thromboembolism and disseminated intravascular coagulation, one of the causes of multiple organ dysfunction syndrome. In addition, the consumption of platelets and coagulation proteins may result in serious bleeding. Patients with sepsis admitted to the ICU have, as their main care providers, the nursing staff that may have their activities organized by the Nursing Care Systematization (NCS). NCS provides perspectives regarding care, guides and regulates more precisely nursing care, directing the resolution of patients' problems, as it mobilizes specific professional skills in care, resulting in the quality of care. This study aimed to evaluate the relationship of two components of the hemostatic system (platelet count and International Normalized Ratio - INR) with clinical severity and outcome in patients diagnosed with ICU sepsis. This is a quantitative, exploratory and correlational study in which data were previously collected. The study was developed in a public hospital of high complexity care at the outpatient and inpatient level through the analysis of medical records of patients diagnosed with sepsis admitted to the ICU from January to December 2017. The variables related to socio-demographic, clinical characteristics and length of nursing care were collected from the patients' electronic medical records using a specific form. We included 176 medical records. No statistically significant differences were observed regarding gender, age or race of patients; however, the results show that patients with death outcome had worse clinical and laboratory parameter values, required more nursing care and had lower platelet count and higher INR than patients who were discharged; in addition, platelet counts <100,000 mm3 and INR> 1.5 were associated with a higher frequency of death outcome. We analyzed the ability of platelet count and INR to predict death by means of a ROC curve that indicated platelet count as an inadequate predictor and INR as a weak predictor of death outcome. Thus, this study showed that patients diagnosed with sepsis who died had greater organic impairment and demanded more nursing care than those who were discharged from the hospital. In addition, the platelet counts and INR indicate a compromised hemostatic system, signaling a fibrinolytic picture. Both platelet count and INR were associated with death; however, they were not good predictors for it. The dimensioning of nursing work using the NAS, the evaluation of laboratory tests and severity on SAPS 3, performed by a nurse with specific knowledge, facilitates the elaboration and evolution of the NCS. The more data, the more accurate the analysis, leading to changes in nursing care planning

Utilización de un dispositivo portátil para monitorear la relación internacional normalizada en pacientes con anticoagulante lúpico positivo / Use of a portable device to monitor the international normalized ratio in patients with positive lupus anticoagulant

La certeza del valor de la relación internacional normalizada (RIN), ensayo para controlar la anticoagulación con dicumarínicos, en pacientes con anticoagulante lúpico positivo (AL) es desconocida especialmente para los dispositivos al lado del paciente (POCT). El objetivo de este trabajo fue investigar si existe correlación entre el valor del RIN obtenido por el método tradicional y el obtenido con un dispositivo portátil en pacientes con AL positivo. Se estudiaron 35 pacientes anticoagulados por enfermedad tromboembólica con diagnóstico de AL positivo persistente a los que se les determinó al mismo tiempo el RIN por el método tradicional y con CoaguChek durante 4 controles consecutivos. El rango del RIN fue 1,9 a 5,60 y el RIN-POCT estuvo entre 2,0 y 4,92. La comparación del RIN vs RIN-POCT mostró r=0,98, pendiente: 1,56 (0,98-1,12) y una ordenada al origen de -0,088 (-0,282-0,007). El sesgo fue 2,1%. Para un nivel del RIN menor de 3,5 (n=136 controles) la diferencia del RIN promedio fue de 0,17 con un rango de 0,01-0,56. Un paciente, con triple positividad, mostró una diferencia entre ambos métodos mayor de 0,4 en dos controles. Para un RIN mayor de 4,5 el grado de concordancia fue menor pero no tiene implicancia clínica. Los resultados del RIN obtenidos por CoaguChek en los pacientes estudiados con AL positivo son útiles para la práctica clínica. Los datos obtenidos demuestran que hay una buena correlación entre el RIN tradicional y el CoaguChek. Por la gran diversidad de los equipos POCT los resultados no son extrapolables a otros dispositivos. Dada la heterogeneidad de los anticuerpos antifosfolípidos, es recomendable probar en cada paciente si hay una buena concordancia entre el RIN tradicional y el RIN-POCT.

The certainty of the value of the international normalized relation (INR) assay to control dicoumarin anticoagulation in patients with positive lupus anticoagulant (LA) is unknown especially for the point of care testing (POCT). The aim of this work was to investigate if there was a correlation between the INR values obtained by the traditional method and those obtained with a POCT in patients with positive LA. The population under study were 35 patients anticoagulated by thromboembolic disease with a persistent positive LA, whose INR was determined at the same time by the traditional method and with CoaguChek during 4 consecutive controls. The INR range was 1.9 to 5.60 and the RIN-POCT was between 2.0-4.92. The comparison of INR vs. INR - POCT showed r=0.98, slope: 1.56 (0.98-1.12) and ordered to the origin -0.088 (-0.282-0.007). The bias was 2.1%. For an INR level lower than 3.5 (n=136 controls) the average INR difference was 0.17 with a range of 0.01-0.56. One patient, with triple positivity showed a difference between both methods greater than 0.4. in two controls. For INR greater than 4.5, the degree of concordance is lower but has no clinical implications. The data obtained show that there is a good correlation between the traditional INR and the CoaguChek. The results of INR obtained by CoaguChek in patients studied with positive LA are useful for clinical practice. Due to the large diversity of POCT, the results cannot be extrapolated to other devices. Given the heterogeneity of antiphospholipid antibodies, it is advisable to test in each patient whether there is a good agreement between the traditional INR and INR-POCT.

A certeza do valor da razão internacional normalizada (RIN ou IIN), ensaio que controla a anticoagulação com dicumarínicos, em pacientes com anticoagulante lúpico positivo (AL) é desconhecida especialmente para os dispositivos de teste do tipo point-of-care (POCT). Este trabalho teve como objetivo pesquisar se existe correlação entre o valor de RIN obtido pelo método tradicional e aquele obtido com um dispositivo portátil em pacientes com AL positivo. Foram estudados 35 pacientes anticoagulados por doença tromboembólica com diagnóstico de AL positivo persistente aos quais lhes determinaram, ao mesmo tempo, a RIN pelo método tradicional e com CoaguChek durante 4 controles consecutivos. O intervalo de RIN foi de 1,9 a 5,60 e o de RIN-POCT ficou entre 2,0 e 4,92. A comparação de RIN vs RIN-POCT mostrou r=0,98, pendente: 1,56 (0,98-1,12) e uma ordenada à origem de -0,088 (-0,282-0,007). O viés foi 2,1%. Para um nível de RIN menor a 3,5 (n=136 controles) a diferença de RIN em média foi de 0,17 com um intervalo de 0,01-0,56. Um paciente, com tríplice positividade, mostrou uma diferença entre ambos os métodos maior a 0,4 em dois controles. Para um RIN de mais de 4,5, o grau de concordância foi menor, mas não tem consequências clínicas. Nos pacientes estudados com AL positivo, os resultados da RIN obtidos por CoaguChek são úteis para a prática clínica. Os dados obtidos demonstram que existe uma boa correlação entre a RIN tradicional e o CoaguChek. Devido à grande diversidade dos equipamentos POCT, os resultados não são extrapoláveis a outros dispositivos. É recomendável, visto a heterogeneidade dos anticorpos antifosfolípídes, provar em cada paciente a existência de uma boa concordância entre a RIN tradicional e a RIN-POCT.

Estudio comparativo de equipos INR capilar "point of care" versus INR venoso, en pacientes en tratamiento con antagonistas de vitamina K / Comparison of point of care capillary international normalized ratio (INR) with INR measured in venous samples

Background: INR is used to monitor the treatment with vitamin K antagonists. A strategy to reduce waiting times for sampling is to measure INR in a capillary sample using a portable point of care (POC) type coagulometer. Aim: To evaluate the correlation of CoaguChek Pro II™, Xprecia™ and microINR™ with venous INR measured at the clinical laboratory and their ease of use. Materials and Methods: Patients provided capillary and venous blood samples for parallel tests comparing Xprecia™ Stride with CoaguChek Pro II™ and with venous INR, microINR™ with CoaguChek Pro IITM and with venous INR. The devices' ease of use was assessed surveying the sampling staff. Results: The three tested devices had good correlation coefficients with venous INR: CoaguChek Pro IITM 0.953 and 0.962; Xprecia™ of 0.912 and microINR™ of 0.932. The correlation coefficient of Xprecia™ with CoaguChek Pro IITM was 0.937 and microINR™ with CoaguChek Pro IITM was 0.976. Conclusions: CoaguChek Pro IITM, Xprecia™ and microINR™ results had a good correlation coefficient with INR measured at the laboratory. Our results indicate that, in the hands of trained users, POC-type coagulometers are reliable and acceptable for routine use in anticoagulant treatment control.

A Case of Spontaneous Rupture of Hepatocellular Carcinoma Supplied by the Right Renal Capsular Artery Treated by Transcatheter Arterial Embolization

We present a case of spontaneous rupture of hepatocellular carcinoma with poor liver function managed by transcatheter arterial embolization (TAE). The patient's bilirubin level was 2.1 mg/dL, albumin level was 2.4 g/dL, and prothrombin time international normalized ratio was 2.1. In addition, the patient had also developed a large number of ascites. The tumor was supplied by the right renal capsular artery, as observed on angiography. With successful TAE, no hepatic failure occurred. We believe TAE can be a safe and effective treatment option, even in patients with poor liver function, if tumors are supplied only by extrahepatic collateral vessels.

Novel Prognostic Nomograms Based on Inflammation-Related Markers for Patients with Hepatocellular Carcinoma Underwent Hepatectomy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Hepatocellular carcinoma (HCC) is an aggressive disease with high recurrence rate. However, current staging systems were lack of predictive capacity for HCC recurrence. We aimed to develop prognostic nomograms based on inflammation-related markers for HCC patients underwent hepatectomy. MATERIALS AND METHODS: We recruited 889 surgically treated patients from two medical centers. Independent prognostic factors were identified by cox regression analyses. Nomograms for recurrence-free survival (RFS) and overall survival (OS) were established, and validated internally and externally. The performance, discrimination, and calibration of nomograms were assessed, and compared with existed staging systems. RESULTS: Neutrophil to lymphocyte ratio (NLR) and gamma-glutamyl transpeptidase to platelet ratio (GPR) were the two inflammation-related factor that independently correlated with survival. NLR, GPR, international normalized ratio (INR), microvascular invasion, satellite lesions, tumour number, tumour diameter, and macrovascular invasion were used to construct nomogram for RFS while GPR, total bilirubin, INR, α-fetoprotein, microvascular invasion, satellite lesions, tumour diameter, and macrovascular invasion were for OS. In the training cohort, the C-index of nomogram was 0.701 (95% confidence interval [CI], 0.669 to 0.732) for RFS and 0.761 (95% CI, 0.728 to 0.795) for OS. These results received both internal and external validation with C-index of 0.701 (95% CI, 0.647 to 0.755) and 0.707 (95% CI, 0.657 to 0.756) for RFS, and 0.706 (95% CI, 0.640 to 0.772) and 0.708 (95% CI, 0.646 to 0.771) for OS, respectively. The nomograms showed superior accuracy to conventional staging systems (p<0.001). CONCLUSION: The nomograms based on inflammation-related markers are of high efficacy in predicting survival of HCC patients after hepatectomy, which will be valuable in guiding postoperative interventions and follow-ups.

Evaluation of Noninvasive Liver Fibrosis Blood Markers in Patients with Chronic Hepatitis B and Hepatitis C

BACKGROUND: Liver fibrosis evaluation is an important issue in chronic liver disease patients. We aimed to develop noninvasive liver fibrosis biomarkers based on transient elastography (TE, FibroScan®) through retrospective review of clinicopathological data. METHODS: We recruited 278 chronic hepatitis B patients who underwent Fibroscan and HBV DNA testing. A total of 115 HBeAg-positive and 159 HBeAg-negative chronic hepatitis B patients were analyzed. A total of 100 hepatitis C patients were analyzed. Successful fibroscan data, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), platelet count, AST, ALT, international normalized ratio of prothrombin time, total cholesterol, triglycerides, bilirubin, mean platelet volume, AST to platelet ratio index, fibrosis index based on four factors (FIB-4), neutrophil to lymphocyte ratio (NLR), and NLR to platelet ratio were analyzed to determine the new noninvasive markers for assessing liver fibrosis. RESULTS: Elevated GPR (OR=9.1, P=0.011) and FIB-4 (OR=2.3, P=0.01) were associated with greater risk of liver fibrosis in chronic hepatitis B patients. FIB-4 (OR=6.04, P=0.005) was a risk factor for liver fibrosis in HBeAg-positive patients. FIB-4 (OR=2.371, P=0.015) and GPR (OR=33.78, P=0.003) were liver fibrosis risk factor in HBeAg-negative patients. In chronic hepatitis C patients, GGT (OR=1.033, P=0.002), triglyceride (OR=−0.990, P=0.038) and FIB-4 (OR=3.499, P=0.006) showed statistical significances. The AUCs were 0.816 in FIB-4 (P<0.001) and 0.849 in GPR (P<0.001). CONCLUSIONS: FIB-4 and GPR may be useful blood markers for assessing liver fibrosis in chronic hepatitis B and hepatitis C patients. Further well-designed prospective study is required to validate these noninvasive blood markers in clinical practice.