RESUMO
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)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos , Hemorragia/induzido quimicamente , Acenocumarol/efeitos adversos , Antibacterianos/efeitos adversos , Anticoagulantes/efeitos adversos , Varfarina/farmacologia , Varfarina/farmacocinética , Fatores de Risco , Medição de Risco , Coeficiente Internacional Normatizado , Interações Medicamentosas , Acenocumarol/farmacologia , Acenocumarol/farmacocinética , Antibacterianos/farmacologia , Anticoagulantes/farmacologia , Anticoagulantes/farmacocinéticaRESUMO
Se presenta el caso clínico de una paciente de 10 años diagnosticada con miocardiopatía dilatada, quien registró valores en el índice internacional normalizado (International Normalized Ratio, INR) superiores a 10 con la dosis estándar de acenocumarol, además de otros valores que indicaban el estado incoagulable, lo que obligó a suspender y reiniciar el tratamiento en varias ocasiones. Después de más de 30 días de tratamiento, sorprendentemente se lograron los niveles esperados y estables en el INR con la mitad de la dosis recomendada para una paciente de su edad y peso.Se decidió hacer un análisis farmacogenético retrospectivo del caso mediante RT-PCR con sondas TaqMan™ que incluyó cinco polimorfismos de un solo nucleótido y distinto grado de asociación con la dosis-respuesta a los fármacos antivitamínicos K (AVK): rs2108622 (gen CYP4F2), rs9923231, rs7294 (gen VKORC1), rs1799853 y rs1057910 (gen CYP2C9). La paciente resultó ser homocigota para el rs9923231 (VKORC1) y heterocigota para el rs2108622 (CYP4F2). Se ha evidenciado a nivel nacional e internacional que este perfil genético está fuertemente asociado con una necesidad de dosis menores de antivitamínicos K.En conclusión, el análisis farmacogenético confirmó que la condición genética de la paciente, la cual conlleva una baja expresión de la enzima VKORC1 (blanco terapéutico de los antivitamínicos K), hacía predecible la necesidad de una dosis menor a la establecida según los protocolos clínicos recomendados por la Food and Drug Administration (FDA) y PharmGKB™ para los fármacos cumarínicos. El análisis genotípico previo de la paciente hubiese permitido alcanzar el rango terapéutico más prontamente, evitando potenciales riesgos de hemorragia, lo que demuestra la importancia de los análisis farmacogenéticos en tratamientos de gran variabilidad y estrecho rango terapéutico.
Abstract We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient's genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.
Assuntos
Farmacogenética , Acenocumarol , Vitamina K , AnticoagulantesRESUMO
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.
Assuntos
Humanos , Tromboembolia , Vitamina K , Anticoagulantes , Tromboembolia/prevenção & controle , Vitamina K/antagonistas & inibidores , Chile , Administração Oral , Acenocumarol , Anticoagulantes/uso terapêuticoRESUMO
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.
Assuntos
Anticoagulantes , Tromboembolia , Vitamina K , Acenocumarol , Administração Oral , Anticoagulantes/uso terapêutico , Chile , Humanos , Tromboembolia/prevenção & controle , Vitamina K/antagonistas & inibidoresRESUMO
We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.
Assuntos
Acenocumarol/efeitos adversos , Anlodipino/efeitos adversos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Metformina/efeitos adversos , Protrombina/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Acenocumarol/administração & dosagem , Administração Intravenosa , Idoso de 80 Anos ou mais , Anlodipino/administração & dosagem , Humanos , Infarto da Artéria Cerebral Média/etiologia , Masculino , Metformina/administração & dosagem , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios XRESUMO
Resumen Introducción: Diversas patologías requieren de tratamiento anticoagulante oral (TACO). Algunos de estos pacientes requieren resolución quirúrgica. El manejo perioperatorio de estos pacientes es variable dependiendo del centro. Objetivos: Evaluar la morbilidad y mortalidad del protocolo de manejo de patología herniaria en TACO, atendidos en nuestro hospital. Material y Métodos: Estudio descriptivo prospectivo de 37 pacientes sometidos a cirugía herniaria en TACO entre 2008-2016. Los datos fueron obtenidos de la base de datos computacional del Equipo de Hernias, con un seguimiento mínimo de 1 mes. Se evaluaron las características clínicas, quirúrgicas y la morbimortalidad postoperatoria. El traslape consistió en hospitalizar al paciente tres días previos a la cirugía, suspendiéndose el TACO e iniciando heparina de bajo peso molecular (HBPM) en dosis terapéuticas, que se suspende 24 h previas a la cirugía. Se reinicia la HPBM a las 12 a 24 h postoperatorias, y se inicia el traslape a TACO a las 24-48 h. Los datos fueron analizados con Stata v14. Resultados: De los 37 pacientes estudiados, veintiséis pacientes fueron hombres (70,2%), la media de edad fue de 67,3 años. El 48,7% tenían fibrilación auricular. El 100% consumía acenocumarol como TACO. La media en el inicio del traslape a la anticoagulación oral fue de 1,4 días. El promedio de INR al momento del alta fue de 2,04. Dos pacientes fueron dados de alta con dalteparina. Un paciente (2,7%), presentó dolor en el postoperatorio inmediato y uno (2,7%), equimosis del sitio quirúrgico. Conclusiones: El protocolo de trabajo utilizado, demostró ser seguro, con una mínima morbilidad postoperatoria.
Introduction: Various pathologies require oral anticoagulant treatment (TACO). Some of these patients present pathologies of surgical resolution. The perioperative management of these patients is variable depending on the center. Aim: To evaluate the morbidity and mortality of patients attended with hernia pathology and TACO, assisted in our hospital. Materials and Method: Prospective, descriptive study of 37 patients submmited to hernia surgery in TACO between 2008-2016. The data was obtained from the computer database of the Hernia Team, with a minimum follow-up of 1 month. Clinical, surgical characteristics and postoperative morbidity and mortality were evaluated. The treatment overlap from TACO to Low Molecular Weight Heparin (LMWH) in therapeutic doses, was initiated three days before surgery. LMWH was suspended 24 hours prior to surgery, and reinitiated 12 to 24 hours post operation. 48 to 72 hours TACO was resumed. The data was analyzed with Stata v14. Results: Twenty-six patients were men, the mean age was 67.3 years. 48.7% had atrial fibrillation. 100% consumed acenocoumarol as TACO. The mean time for resuming TACO after surgery was 1.4 days. The average INR at the time of discharge was 2.04. Two patients were discharged with dalteparin. One patient (2.7%) presented pain in the immediate postoperative period and one showed ecchymosis of the surgical site (2.7%). Conclusions: The work protocol used, proved to be safe, with minimal postoperative morbidity.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Eletivos/métodos , Herniorrafia/métodos , Anticoagulantes/efeitos adversos , Período Pós-Operatório , Herniorrafia/efeitos adversos , Herniorrafia/mortalidade , Hérnia/complicações , Acenocumarol/efeitos adversosRESUMO
We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.
Assuntos
Humanos , Masculino , Idoso de 80 Anos ou mais , Protrombina/administração & dosagem , Terapia Trombolítica/métodos , Anlodipino/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Acenocumarol/efeitos adversos , Metformina/efeitos adversos , Tomografia Computadorizada por Raios X , Anlodipino/administração & dosagem , Acidente Vascular Cerebral/etiologia , Infarto da Artéria Cerebral Média/etiologia , Administração Intravenosa , Acenocumarol/administração & dosagem , Metformina/administração & dosagemRESUMO
El hematoma epidural espontáneo es una entidad muy poco frecuente que supone una urgencia neurológica. Su presentación es muy variable, desde un dolor de espalda hasta una tetraplejia, según la gravedad y el nivel de compresión. Se comunica el caso de un paciente cardiópata de 71 años, tratado con acenocumarol, que presentó un hematoma epidural de modo espontáneo. Al inclinarse hacia el suelo, el paciente, que no tenía síntomas, sufrió un dolor brusco cervical seguido de debilidad en los miembros superiores e inferiores. Ante la sospecha clínica de una compresión medular, se decide realizar una resonancia magnética de urgencia, que mostró un hematoma de localización epidural con extensión desde C4 hasta T8. El diagnóstico urgente y el tratamiento de descompresión precoz son fundamentales para reducir al mínimo los daños neurológicos posteriores permanentes. Nivel de Evidencia: IV
Spontaneous spinal epidural hematoma is an uncommon condition and a neurological emergency. The clinical presentation of this type of hematoma is very variable, ranging from a backache up to a quadriplegia, according to the severity and the site of compression. Here, we discuss the clinical case of a 71-year-old patient with heart problems, under previous treatment with acenocumarol, that suffered a spontaneous epidural hematoma. The patient, previously asymptomatic, presented, sudden cervical pain when he bent over, followed by weakness in the lower and the upper limbs. Due to the clinical suspicion, an emergency MRI was performed, showing an epidural hematoma extending from C4 to T8. Early diagnosis and decompressive treatment are mandatory to minimize permanent neurological damage. Level of Evidence: IV
Assuntos
Idoso , Doenças da Coluna Vertebral , Descompressão Cirúrgica/métodos , Hematoma Epidural Espinal/cirurgia , Tratamento de Emergência , Acenocumarol/efeitos adversosRESUMO
Aunque la causa más frecuente de rotura esplénica es la traumática, podemos encontrar roturas sin relación a un traumatismo previo. Se está objetivando un aumento de roturas espontáneas en relación con tratamiento anticoagulante. Presentamos el caso de un hombre en tratamiento con acenocumarol que presentó una rotura espontánea esplénica que requirió esplenectomía urgente. La rotura de bazo es una entidad grave que debe considerarse ante todo paciente con un abdomen agudo. Aunque las causas más frecuentes de rotura esplénica atraumática son las complicaciones neoplásicas e infecciosas, se han objetivado varios casos asociados a terapias antiagregantes y anticoagulantes. Dado el aumento de población que precisa anticoagulación oral, la sobredosificación con acenocumarol debe considerarse como una posible causa de rotura esplénica. Debemos sospechar esta entidad ante todo paciente en tratamiento con anticoagulación oral con un abdomen agudo.
The splenic rupture is most commonly related to trauma, but spontaneus ruptures have also been described with increasing frequency. We present a case of a male patient with spontaneous splenic rupture due to oral anticoagulant overdose that required urgent splenectomy. The spontaneous splenic rupture is a life-threatening condition that must be considered in patients with acute abdomen. Although most ruptures are associated with to neoplastic and infectious complications , recent reports have related rupture with anticoagulant and antiaggregant therapies. Moreover, since the number of patients undergoing oral anticoagulant therapies is growing, overdose of anticoagulant drugs must be considered as a possible ethiology of spontaneous splenic rupture and suspect this association in patient with acute abdomen undergoing anticoagulant therapy.
Assuntos
Humanos , Masculino , Ruptura , Baço , Acenocumarol , Associação , Ferimentos e Lesões , Causalidade , Abdome Agudo , AnticoagulantesRESUMO
Resumen Introducción: la escala SAMe-TT2R2 ha sido propuesta para predecir la calidad de la anticoagulación con antagonistas de la vitamina K. Objetivo: validar la capacidad discriminativa de la escala SAMe-TT2R2 en una cohorte de pacientes con fibrilación auricular no valvular de la vida real. Métodos: estudio observacional de pacientes con fibrilación auricular no valvular tratados con antagonistas de la vitamina K al menos seis meses. Se consideró buen control de anticoagulación un tiempo en rango terapéutico ≥ 65% estimado con el método de Rosendaal. Se evaluó la asociación entre puntuación SAMe-TT2R2 y el control de anticoagulación con regresión logística binaria. La capacidad de discriminación se analizó mediante el cálculo del valor del área bajo la curva ROC. Resultados: se incluyeron 241 pacientes de edad media 78,6±8,6 años, 53% mujeres. La media del tiempo en rango terapéutico fue 59,4±25,4%, menor según aumentó la puntuación SAMe-TT2R2. En general, la escala no mostró capacidad para discriminar los pacientes con adecuado control de anticoagulación: área bajo la curva ROC 0,57 (IC95%:0,49-0,64, p=0,06). Solo fue útil para las puntuaciones extremas, con probabilidad de buen control del 65,1% vs. 34,9%, p=0,01 para valor 0 y del 0% vs. 100%, p=0,03 para ≥ 4. La razón de disparidad de tener un tiempo en rango terapéutico <65% para puntuación ≥2 fue de 1,22 (IC95%:0,73-2,02, p=0,44). Conclusión: en una cohorte de pacientes con fibrilación auricular no valvular y datos de la vida real la escala SAMe-TT2R2 no mostró, globalmente, capacidad discriminatoria para control adecuado de anticoagulación con antagonistas de vitamina K. Solo se mostró útil para clasificar correctamente los casos con puntuaciones extremas.
Abstract Introduction: The SAMe-TT2R2 score has been proposed to predict the quality of anticoagulation with vitamin K antagonists. Objective: To validate the discriminatory power of the SAMe-TT2R2 score real-life in a patient cohort with non-valvular atrial fibrillation. Material and methods: An observational study was conducted on patients with non-valvular atrial fibrillation treated with vitamin K antagonists for at least six months. Good anticoagulation control was considered a time in the therapeutic range of ≥ 65%, estimated with the Rosendaal method. The relationship between the SAMe-TT2R2 score and the anticoagulation control was evaluated using a binary logistic regression. The discriminatory power was determined using the calculation of the value of the area under the ROC curve. Results: The study included total of 241 patients, with a mean age of 78.6±8.6 years, and 53% women. The mean time in the therapeutic range was 59.4±25.4%, low according to the increase in the SAMe-TT2R2 score. In general, the scale did not appear to have the power to discriminate patients with adequate anticoagulation control, with an area under the ROC curve of 0.57 (95% CI: 0.49-0.64, P=.06). It was only useful for extreme scores, with a probability of good control of 65.1% vs. 34.9%, P=.01 for a value of 0, and of 0% vs. 100%, P=.03 for ≥ 4. The disparity ratio of having a time in the therapeutic range of <65% for a score ≥2 was 1.22 (95% CI: 0.73-2.02, P=.44). Conclusion: In a cohort of patients with non-valvular atrial fibrillation and with real-life data, the SAMe-TT2R2 scale, did not, on the whole, show discriminatory power for the adequate control of anticoagulation with vitamin K antagonists. It only showed to be useful to correctly classify the cases with extreme scores.