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)

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

Uso de varfarina em pediatria: características clínicas e farmacológicas / Use of warfarin in pediatrics: clinical and pharmacological characteristics

RESUMO Objetivo: Descrever como as crianças respondem à anticoagulação oral com varfarina, verificando a influência da idade, da condição clínica, da via de administração da varfarina e do uso de Nutrição Parenteral Total (NPT), e apresentar a presença de fatores de risco para eventos tromboembólicos (TE). Métodos: Estudo transversal retrospectivo com pacientes ≤18 anos que iniciaram o uso da varfarina em um hospital universitário. Os pacientes foram divididos conforme condição clínica, idade, forma de administração do medicamento e uso de NPT. Foram utilizados os dados dos prontuários dos pacientes, considerando os fatores de risco para TE já descritos na literatura, o tempo e a dose necessária para atingir a primeira Razão Normalizada Internacional (INR) no alvo e eventos adversos nesse período. No período posterior ao alcance de INR, foi verificada a manutenção da anticoagulação, por meio da dose prescrita e dos exames de INR. Resultados: Vinte e nove pacientes foram incluídos no estudo. O principal fator de risco para TE foi o uso de cateter venoso central, em 89,6% dos pacientes. Os pacientes com síndrome do intestino curto e em uso de NPT necessitaram de doses significativamente maiores (p≤0,05) para atingir e manter a INR no alvo. Os pacientes com ≤1 ano levaram mais tempo e necessitaram de uma dose maior para anticoagular e para manter o INR no alvo que os pacientes mais velhos. A mediana de exames de INR abaixo do alvo foi de 48,2% nos grupos estudados. Conclusões: A complexidade da terapia anticoagulante reforça a necessidade da elaboração de protocolos que orientem a prática clínica.

ABSTRACT Objective: To describe how children respond to oral anticoagulation with warfarin, verifying the influence of age, clinical condition, route of administration of warfarin and use of total parenteral nutrition (TPN), as well as to describe risk factors for the occurrence of thrombotic events (TE) in childhood. Methods: A retrospective descriptive study including all patients ≤18 years old for whom warfarin was prescribed in a university hospital. Patients were divided according to clinical condition, age, route of medication administration and use of TPN. Data was collected from the patients' medical records and the analysis considered the risk factors for TE already described in the literature, the time and the dose required in order to reach the first International Normalized Ratio (INR) in the target and the adverse events in this period. After reaching the INR, the maintenance of anticoagulation was verified by the prescribed dose and INR tests. Results: Twenty-nine patients were included in the study. The major risk factor for TE was the use of a central venous catheter in 89.6% of the patients. Patients with short bowel syndrome and total parenteral nutrition required significantly higher doses (p≤0.05) to achieve and maintain the INR in the target. Patients ≤1 year old needed longer periods and required an increased dose of anticoagulation and maintenance than older patients. The mean number of INR examinations below the target was 48.2% in the groups studied. Conclusions: The observed complexity of anticoagulant therapy reinforces the need to develop protocols that guide clinical practice.

Analysis of Novel Anticoagulants for Atrial Fibrillation – Pharmacokinetics and Pharmacological Considerations.

Atrial Fibrillation (AF) is the most common arrhythmia. AF is a major risk factor for stoke. Warfarin has been available for more than 60 years and until recently it was the only oral anticoagulant used for the prevention of stroke. Despite the extensive studies and proven efficacy, its utility is limited by multiple factors. Warfarin interacts with a multitude of drugs and foods, has a delayed onset of action, has a narrow therapeutic range, requires routine lab monitoring and exhibits variable responses in patients. The novel agents dabigatran, rivaroxaban and apixaban have the potential to have some of the limitations of warfarin. This article will discuss the pharmacokinetic and pharmacological considerations and different characteristics of the novel anticoagulants when used for the prevention of AF.

Avaliação da estabilidade de anticoagulação entre a Varfarina e a Femprocumona / Oral anticoagulation stability assessment with Warfarin and Phenprocoumon

Fundamentos: A varfarina e a femprocumona são os anticoagulantes orais mais utilizados; no entanto, até então, não existem estudos randomizados comparando a estabilidade da anticoagulação entre estes dois fármacos. Objetivos: Comparar a varfarina e femprocumona quanto à estabilidade na manutenção de anticoagulação em nível terapêutico (razão normatizada internacional [RNI] entre 2,0 e 3,0) e avaliar a incidência de complicações hemorrágicas e tromboembólicas decorrentes de anticoagulação inadequada.Métodos: Ensaio clínico, randomizado, duplo-cego, incluindo pacientes em tratamento vigente com anticoagulante oral, porém com RNI abaixo do alvo terapêutico nas últimas três semanas, randomizados para uso de varfarina ou femprocumona. O ajuste da dose da medicação foi realizado conforme algoritmo pré-estabelecido. Resultados: Foram randomizados 62 pacientes, sendo 31 em cada grupo, durante as cinco primeiras semanas de estudo. Verificou-se que a femprocumona se mostrou mais instável comparada à varfarina. A partir da sexta aferição de RNI, o grupo femprocumona apresentou melhora na estabilidade do valor do RNI, porém não houve significância estatística. Também não houve diferença significativa em relação aos efeitos colaterais dos fármacos. Conclusão: A varfarina demonstrou maior eficácia na estabilidade do RNI em relação à femprocumona.

Background: Although warfarin and phenprocoumon are the most widely used oral anticoagulants, there a r e n o r a n d o m i z e d s t u d i e s c o m p a r i n g t h e anticoagulation stability of these two drugs.Objectives: To compare warfarin and phenprocoumon in terms of therapeutic anticoagulation maintenance stability (international normalized ratio [INR] between 2.0 and 3.0) and evaluate the incidence of thromboembolic and hemorrhagic complications arising from inadequate anticoagulation.Methods: Randomized double-blind clinical trial with patients undergoing current oral anticoagulant treatment but with INR below the therapeutic target during the past 3 weeks, randomized for warfarin or phenprocoumon. Medication dosages were adjusted in compliance with a predetermined algorithm.Results: With 62 patients randomized into two groups of 31 each during the first five weeks of the study, phenprocoumon was found to be more unstable than warfarin. From the sixth INR measurement onwards, the stability of the INR value improved in the phenprocoumon group, but with no statistical significance. There were no significant differences in the side effects of the drugs.Conclusion: Warfarin demonstrated greater effectiveness for INR stability than phenprocoumon.

Warfarin: pharmacological profile and drug interactions with antidepressants / Varfarina: perfil farmacológico e interações medicamentosas com antidepressivos

Oral anticoagulants are among the drugs with the greatest number of drug interactions. The concomitant use of several medications is a common practice in patients with cardiovascular problems, who often also present with depression; therefore, the probability of an interaction occurring between warfarin and the antidepressants is high, and may result in increased or decreased anticoagulant activity. Since the possible interactions between these two classes of drugs have been poorly explored in literature, with a risk to the patients who use them, we reviewed the pharmacology of warfarin and its possible interactions with antidepressants. Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.

Os anticoagulantes orais estão entre as drogas com maior número de interações medicamentosas. O uso concomitante de vários medicamentos é uma prática comum em pacientes com problemas cardiovasculares, os quais frequentemente também apresentam depressão; assim, a probabilidade de ocorrer alguma interação entre a varfarina e os antidepressivos é bem expressiva, podendo resultar em um aumento ou uma diminuição da atividade anticoagulante. Como as possíveis interações entre essas duas classes de medicamentos se mostraram pouco exploradas na literatura, com risco aos pacientes que fazem uso delas, revisamos a farmacologia da varfarina e suas possíveis interações com antidepressivos. Dos antidepressivos analisados, os que apresentaram efeitos relevantes na interação com a varfarina foram, em ordem decrescente: paroxetina, venlafaxina, fluoxetina e duloxetina.

CYP2C9 polymorphism studies in the Saudi population

To determine the prevalence of CYP2C9 polymorphism in normal Saudis [controls], in Saudi patients with venous thrombosis, in patients requiring low dose warfarin [study group] for anticoagulation, and to compare our results to those from other populations. Blood from the "control and study" groups was collected from November 2001 to November 2008. The DNA was extracted, stored at -70°C and later tested for the CYP2C9 polymorphism using established methods. Clinical data were collected through direct interview, chart review, and the Saudi Thrombosis and Familial Thrombophilia Registry. All individuals consented. The prevalence of CYP2C9 polymorphisms in the Saudi population was similar to Caucasians and higher than Asian and African. The control [n=670] and patients with venous thrombosis [n=110] groups showed similar prevalence of the normal wild type CYP2C9 and the 2 polymorphisms tested [CYP2C9*2 and CYP2C9*3]. The group that required low dose warfarin [n=25] showed significantly higher CYP2C9 polymorphism, required 40% less warfarin and had a higher rate of bleeding [5% versus 1.8%]. The prevalence of the abnormal polymorphism in the Saudi population of 35.5% is similar to that in Caucasians. Patients with the CYP2C9 polymorphism required 40% less warfarin and had more serious bleeds

Consulta especializada de anticoagulación del Centro Cardiovascular Regional Ascardio: Barquisimeto-Venezuela / Specialized consult of Anticoagulation of the Regional Cardiovascular Center Ascardio: Barquisimeto-Venezuela

La terapia anticoagulante representa un recurso terapéutico fundamental en la prevención y tratamiento de la enfermedad tromboembólica, y para su éxito es indispensable el seguimiento estricto. Presentar la metodología de trabajo de la Consulta especializada de anticoagulación del Centro Cardiovascular Regional Ascardio. Descripción de las características generales de trabajo, estructura, objetivos, criterios de admisión, limitantes de ingreso, protocolo y estadísticas generales, en más de una década de experiencia. Se incluye la estadística generada en 12 años de experiencia con 2774 pacientes. La distribución por genero de los pacientes es similar. Dos tercios de los mismos se encuentra en la cuarta y octava década de su vida. Casi la mitad son analfabetas, y 9 de cada 10 tienen nivel socioeconómico medio bajo o bajo. El diagnóstico de referencia más frecuente es fibrilación auricular, seguido de tromboembolismo venoso, que representan dos terceras partes de los diagnósticos de ingreso. La consulta especializada de anticoagulación del CCR-Ascardio ha cubierto la creciente demanda de pacientes con terapia antitrombólica, quienes ameritan un seguimiento suficiente y estricto. La metodología de trabajo desarrollada, facilito el registro y análisis del comportamiento de los pacientes con esta terapia, Se busca incentivar el establecimineto en otros centros de atención médica, y satisfacer la necesidad de servicio de salud creciente.

Oral Anticoagulant Therapy represents a fundamental of thromboembolic disease, and for its success, strict adherence is indispensable. To present the approach used at the Specialized Anticogulation in the Regional Cardiovascular Center-Ascardio. Description of general characteristics, etructure, objetives, requirements for patient enrollment, limitations of enrollment, work protocol and general statistics of over a decade of experience. The article includes the statistics of 12 year's experience, with 2774 patients. The distribution by gender is similar. Two thirds of patients are between the fourth and eighth decade of life. Almost half are illiterate, and 9 out of 10 are from a low social economic level. The most frequent referral diagnósis is Atrial Fibrillation, followed by Venous Thromboembolism. In addition, the two referral diagnosis two thirds of the admission diagnostic. The Specialized Anticoagulation responded to the Regional Cardiovascular Cnter-Ascardio has covered the growing demand of patients receiving antithrombothic thrapy, who need strict and satisfactory monitoring. The approach that has beeb developed has helped with registration and analysis of the behavior of patients with this therapy. A future objetive is to promote such services in other health care centers in order to meet this growing health care need.

Assessment of anticoagulant effect of evening primrose oil

Effect of evening primrose oil [EPO] was assessed on coagulation parameters following 30 and 60 days administration of 90, 180 and 360 micro l/kg oil to healthy rabbits of either sex. There was significant increase in all assays except Fibrinogen time. These effects might be due to inactivation or inhibition of factors affecting coagulation. The intake of evening primrose oil also significantly decreased platelet count. Results of this study suggest that evening primrose oil shows considerable anti-anticoagulant and anti-platelet activity in animals and has potential to reduce cardiovascular morbidity and mortality

Varfarina previne obstruções venosas pós-implante de dispositivos cardíacos em pacientes de alto risco: análise parcial / Warfarin prevents venous obstruction after cardiac devices implantation in high-risk patients: partial analysis

OBJETIVOS: Avaliar a utilidade da varfarina na prevenção dessas complicações nos pacientes de alto risco. MÉTODOS: Estudo clínico prospectivo, randomizado, cego, em pacientes submetidos ao primeiro implante transvenoso de DCEI, com FEVE<0,40 e/ou MPT ipsilateral ao implante definitivo. Após o procedimento, os pacientes foram randomizados para o uso diário de placebo ou varfarina. Avaliações clínicas e laboratoriais foram realizadas periodicamente. A pesquisa de obstruções venosas foi feita pela venografia por subtração digital, seis meses após o implante. De fevereiro de 2004 a novembro de 2006, foram selecionados 101 pacientes, havendo homogeneidade das características clínicas e operatórias de ambos os grupos (P=NS). RESULTADOS: No grupo Varfarina, 31,4 por cento dos pacientes apresentaram obstruções venosas em comparação a 57,1 por cento do grupo Placebo (RR= 0,57; IC 95 por cento= 0,33 a 0,98; P= 0,015). No grupo Varfarina, 72 por cento dos exames de INR realizados encontraram-se em nível terapêutico. Houve um caso de sangramento gastrintestinal, que justificou a interrupção do uso da varfarina e mudança para o grupo Placebo. CONCLUSÃO: Os resultados preliminares mostraram que o uso profilático da anticoagulação mostrou-se seguro e reduziu significativamente a incidência de obstruções venosas pós-implante de DCEI nos pacientes de alto risco.

OBJECTIVES: To evaluate the efficacy of prophylactic use of warfarin in patients with high risk of lead-associated thrombosis. METHODS: Clinical, prospective, randomized and blinded study, in patients submitted to first transvenous leads implantation with LVEF <0.40 and/or previous ipsilateral temporary pacing. After device implantation, patients were randomly assigned to placebo or warfarin. Periodical clinical and laboratorial evaluations were performed to anticoagulant management. After a six-month period, every patient was submitted to a digital subtraction venography. From February 2004 to November 2006, 101 patients underwent randomization. Baseline characteristics were similar in both groups (P=NS). RESULTS: Venographic analysis showed 31.4 percent of venous obstructions in patients assigned to warfarin as compared with 57.1 percent in patients assigned to placebo (RR= 0.57 [95 percent CI, 0.33 to 0.98]; P=0.015). In the warfarin group, 72 percent of the PT/INR tests were in therapeutic INR range. Only one patient required warfarin discontinuation and cross-over to placebo group due to gastrointestinal bleeding. CONCLUSIONS: These preliminary results showed that the anticoagulation therapy has been safe and reduced the frequency of venous thrombosis after transvenous cardiac devices implantation in high risk patients.

A Case Report of a Patient Carrying CYP2C9*3/4 Genotype with Extremely Low Warfarin Dose Requirement

We report a case of intolerance to warfarin dosing due to impaired drug metabolism in a patient with CYP2C9*3/*4. A 73-yr-old woman with atrial fibrilation was taking warfarin. She attained a high prothrombin time international normalized ratio (INR) at the standard doses during the induction of anticoagulation and extremely low dose of warfarin (6.5 mg/week) was finally chosen to reach the target INR. Genotyping for CYP2C9 revealed that this patient had a genotype CYP2C9*3/*4. This is the first Korean compound heterozygote for CYP2C9*3 and *4. This case suggests the clinical usefulness of pharmacogenetic testing for individualized dosage adjustments of warfarin.

Anticoagulação nas disfunções valvares / Anticoagulation of dysfunction valves

A doença valvar está associada a duas importantes ocorrências: tromboembolismo e desadaptação hemodinâmica. Ambas modificam a qualidade de vida. Desadaptação hemodinâmica altera a capacidade funcional...

Uso de écido tranexámico en pacientes anticoagulados durante cirugía oral / Use of tranexamic acid in anticoagulated patients during oral surgery

En este estudio se observó el tipo de manejo más adecuado para pacientes anticoagulados oralmente, comparando el ácido tranexámico y una sustancia placebo durante cirugía bucal menor; además, se analizó si variables como edad, sexo, dosis de anticoagulante, tiempo de anticoagulación, constante internacional de normalización (INR) y tipo de tratamiento, influyen en el sangrado que se presenta. Este fue un estudio descriptivo con diseño no experimental. Se tomó una muestra de personas (N=30) de una población de pacientes (N=1300) que requerían un procedimiento menor en cavidad bucal que implicara sangrado, y cumplieran con los parámetros de inclusión determiandos previamente. Se realizó historia clínica e interconsulta previa a los cuatro tipos de tratamientos. Para el análisis de los resultados se utilizaron estadísticas descriptivas e inferenciales. Los resultados fueron: el uso de ácido tranexámico redujo el sangrado en el 90 por ciento de los casos, mientras que la sustancia placebo redujo en un 3 por ciento el sangrado; el nivel de INR y el tratamiento influyeron en un 100 por ciento, mientras que otras variables como sexo, edad, tiempo de consumo de anticoagulantes, dosis y conducta médica influyeron en un 10 por ciento. Se concluyó que el ácido tranexámico es eficaz para disminuir la hemorragia en pacientes anticoagulados; el nivel de INR y el tratamiento influyen significativamente en el tipo de sangrado que se presenta. Para el tratamiento debe tenerse en cuenta el INR que el paciente refiere con el fin de prevenir posibles complicaciones que pueden presentarse

Efeitos do uso materno de warfarin no feto: relato de caso / Fetal warfarin syndrome: case report

Os autores descrevem uma criança que apresenta sinais clinicos compativeis com embriopatia por warfarin. Os principais achados säo facies peculiar com hipoplasia nasal, membros encurtados e presença de calcificaçöes peri-epifisárias no estudo radiológico. A patogenese da embriopatia e recomendaçöes terapeuticas para as mulheres que necessitam fazer uso de anticoagulante oral durante a gestaçäo, säo discutidas

Fibrilaçäo atrial: abordagem farmacológica atual / Atrial fibrilation: current pharmacologic approach

Os autores destacam a abordagem farmacológica atual da fibrilaçäo atrial, enfatizando o controle da resposta ventricular, a cardioversäo química e a conduta na prevençäo de eventos troboembólicos de uma anticoagulação adequada

Actividad rodenticida de cuatro drogas anticoagulantes / Rodenticide activity of four anticoagulants drugs

Con el propósito de determinar, analizar y comparar el efecto rodenticidad de cuatro drogas anticoagulantes, se sometió a grupos de Rattus norvegicus línea Sprague Dawley no resistentes a drogas anticosagulantes, en tres períodos (2, 3 y 5 días respectivamente), con warfarina, clorafacinona, coumatetralyl y brodifacoum. Para este efecto se trabajó con 110 ratas cepa blanca. Luego, se analizaron y compararon los consumos de cebos para las 4 drogas, determinándose las mortalidades por ingestión de éstas. Se observaron las principales alteraciones anatomopatológicas. Los resultados del experimento muestran disminución significativa (p< 0,05) del consumo de cebo para tratamiento con coumatetralyl en período de 3 y 5 días de cebado, warfarina en el período de 5 dias de cebado y brodifacoum en dos días de cebado. Esta dosificación resultó ser la más eficiente con una mortalidad de 100 por ciento. Coumatetralyl también resultó ser eficiente, provocando 100 por ciento de mortalidad a partir de tres días de cebado, clorafacinona, fue menos eficiente, ya que se logró un 100 por ciento de mortalidad sólo a partir del 5º día de cebado. Se observó alteraciones anatomopatológicas tales como: congestión pulmonar, cardíaca y hepática, esplenomegalia y hepatomegalia. La sangre se observó de color rojo oscuro y sin coagular

Warfarin resistance in a patient with prosthetic valve endocarditis treated with cloxacillin

Systemic anticoagulation with warfarin is the mainstay therapy for patients with valve prosthesis. Such drug therapy is of crucial importance in patients with prosthetic valve endocarditis [PVE] because of higher incidence of thrombo-embolism. We are reporting a case of PYE where the patient developed warfarin resistance due to Cloxacillin administration in spite of concomitant administration of I.V. Heparin. Warfarin dose was increased from a baseline of 5 mg daily before Cloxacillin was started to 30 mg daily during Cloxacillin treatment. Six weeks after completion and discontinuing the antibiotic course, the patient's International Normalized ratio [INR] value gradually increased and Warfarin dose was tapered down over eight days. Cloxacillin-Warfarin interaction seems to be due to rapid metabolism in susceptible subjects leading to a reduction in the hypoprothombinemic effect of warfarin. Our finding is consistent with the reported cases which documented such interaction with other members of Penicillinase-resistant Penicillins such as NafcilIin and Dicloxacillin