Clinical practice guideline of the spanish society of oral surgery for oral surgery in patients with coagulation disorders / Guía de práctica clínica de la sociedad española de cirugía bucal para cirugía oral en pacientes con trastornos de la coagulación

Background: The number of patients treated with coagulation disorders, and more specifically with anticoagulanttherapy, has increased worldwide in recent years due to increased life expectancy in developed countries. Theprotocols for managing this type of patient in oral surgery has varied over recent years, especially after the appear-ance of new direct-acting oral anticoagulants (DOACs). The assessment of risk of bleeding in this type of patientwhen undergoing a surgical procedure continues to be a controversial issue for patients, dentists and general prac-titioners. The objective of this document is to offer recommendations, based on evidence, for decision making forpatients with coagulopathies who require dental surgical intervention. Material and Methods: Based on the indications of the “Preparation of Clinical Practice guidelines in the NationalHealth System. Methodological manual”, we gathered a group of experts who agreed on 15 PICO questions basedon managing patients with coagulation disorders in dental surgical procedures, such as fitting of implants or dentalextractions.Results: The 15 PICO questions were answered based on the available evidence, being limited in most cases due tothe lack of a control group. Two of the PICO questions were answered by the experts with a grade C recommendation,while the rest were answered with grade D.Conclusions: The results of this review highlight the need to undertake well designed clinical trials with controlgroups and with a representative sample size.(AU)

Healing effect of warfarin in the course of cerulein-induced acute pancreatitis in rats.

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1ß, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

Healthcare resources and costs associated with nonvalvular atrial fibrillation in Spain: apixaban versus acenocoumarol.

Aim: Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. Methods: This is an observational and retrospective study on patients with NVAF who started their treatment with apixaban or acenocoumarol between 1 January 2015 and 31 December 2017. Results: 2160 patients treated with apixaban were paired (1:1) with patients treated with acenocoumarol (propensity score matching). Apixaban reduced the incidence of strokes and systemic embolisms, minor and major bleedings and deaths, versus acenocoumarol. Apixaban led to reductions of 80, 55 and 43% in costs related to nursing visits, hospitalizations, and emergency visits, respectively, leading to annual cost savings of €274/patient, from the perspective of society. Conclusion: Our results suggested that apixaban is a cost-effective alternative for patients with NVAF.

Acenocoumarol Exerts Anti-Inflammatory Activity via the Suppression of NF-κB and MAPK Pathways in RAW 264.7 Cells.

The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic indications against human diseases. The current study aimed to assess the repurposing of the anticoagulant drug acenocoumarol for the treatment of chronic inflammatory diseases (e.g., atopic dermatitis and psoriasis) and investigate the potential underlying mechanisms. For this purpose, we used murine macrophage RAW 264.7 as a model in experiments aimed at investigating the anti-inflammatory effects of acenocoumarol in inhibiting the production of pro-inflammatory mediators and cytokines. We demonstrate that acenocoumarol significantly decreases nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Acenocoumarol also inhibits the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2, potentially explaining the acenocoumarol-induced decrease in NO and PGE2 production. In addition, acenocoumarol inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), c-Jun N terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), in addition to decreasing the subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicates that acenocoumarol attenuates the macrophage secretion of TNF-α, IL-6, IL-1ß, and NO, inducing iNOS and COX-2 expression via the inhibition of the NF-κB and MAPK signaling pathways. In conclusion, our results demonstrate that acenocoumarol can effectively attenuate the activation of macrophages, suggesting that acenocoumarol is a potential candidate for drug repurposing as an anti-inflammatory agent.

Azathioprine and Acenocoumarol Drug Interaction in Patients with Crohn's Disease: A Case Report.

BACKGROUND: Acenocoumarol is an anticoagulant with numerous drug reactions. We report here, an unusual interaction between acenocoumarol and azathioprine. CASE PRESENTATION: A 35-year-old woman, treated with acenocoumarol for thrombosis of the superior mesenteric vein, was prescribed azathioprine for Crohn's disease. Three days later, INR values decreased from 2.36 to 1.48. The dose of acenocoumarol had to almost be doubled to reach an INR value of 2.56. The interaction between azathioprine and acenocoumarol was then suspected. Few similar cases of interactions between azathioprine and another coumarin derivative, warfarin, have been reported. To our knowledge, this is the second case of such interaction reported with acenocoumarol in literature. CONCLUSION: Thus, despite the rarity of this interaction reporting, we draw attention to the importance of close monitoring of INR values in patients treated with acenocoumarol associated with azathioprine.

Predicting Glioma Cell Differentiation-inducing Drugs Using a Drug Repositioning Strategy.

BACKGROUND: Currently, there are no effective differentiation-inducing agents for gliomas. Drug repositioning is a time-saving, low-risk, and low-cost drug development strategy. In this study, drugs that could induce the differentiation of glioma cells were searched by using a drug repositioning strategy. METHODS: Data mining was used to screen for differentially expressed genes (DEGs). The STRING 11.0 database was used for enrichment analysis. The Connectivity Map database was used for drug screening. The ChEMBL and STITCH databases were used to search for drug targets. The SwissDock database was used for molecular docking. RESULTS: A total of 45 DEGs were identified. The biological processes in which the DEGs were enriched mainly involved nervous system development and the regulation of biological processes. The enriched molecular functions mainly involved transcription-related molecular binding. The enriched cellular components mainly involved membrane-bound organelles and cellular protrusions. The enriched local network clusters mainly involved autophagy, the retinoic acid signalling pathway, and DNA methylation. The drug screening results showed that the drug with the highest score was acenocoumarol. A total of 12 acenocoumarol targets were obtained, among which histone deacetylase 1 (HDAC1) was the target with the highest degree value; the lowest ΔG value for acenocoumarol docked with HDAC1 was -7.52 kcal/mol, which was between those of the HDAC1 inhibitors romidepsin and vorinostat. CONCLUSION: Acenocoumarol may be a potential differentiation-inducing agent for glioma cells.

Rivaroxaban plus aspirin versus acenocoumarol to manage recurrent venous thromboembolic events despite systemic anticoagulation with rivaroxaban.

INTRODUCTION: The evaluation and management of patients who sustain recurrent thromboembolic events while taking therapeutic anticoagulation have not been well characterized; moreover, there has been no systematic review or randomized trial focused on treating patients with recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) during anticoagulant treatment. Therefore, we developed a pilot trial to compare rivaroxaban plus aspirin versus acenocoumarol in patients with recurrent venous thromboembolism despite ongoing anticoagulation with rivaroxaban. MATERIALS AND METHODS: The study was a multicenter, randomized clinical trial. We randomly assigned patients with objectively documented recurrent venous thromboembolism to receive rivaroxaban (20 mg once a day) plus aspirin (300 mg once a day) or an adjusted dose of acenocoumarol. The study was designed to evaluate the incidence of recurrent thromboembolic events (recurrent ipsilateral or contralateral DVT, PE, ischemic stroke, and myocardial infarction) and hemorrhagic events. RESULTS: A total of 58 patients were randomized: 28 were allocated to the rivaroxaban plus aspirin group and 30 to the acenocoumarol group. After 90 days of follow-up, three recurrent thromboembolic events (primary outcome) occurred in the acenocoumarol group - two DVTs and one ischemic stroke - and zero events in the rivaroxaban plus aspirin group (risk ratio [RR] 0.15; 95 % confidence interval [CI] 0.008-2.83; P = 0.20). Minor bleeding occurred in five patients in the acenocoumarol group and zero in the rivaroxaban plus aspirin group (RR 0.09; 95 % CI 0.005-1.68; p = 0.10). There was one non-fatal gastrointestinal major bleed in the rivaroxaban plus aspirin group. CONCLUSIONS: In this pilot study, there were no significant differences in any outcome assessed; however, recurrent thromboembolic events and minor bleeding events occurred numerically less frequently in the rivaroxaban plus aspirin group. These data suggest the need to carry out more extensive randomized studies with sufficient statistical power to clarify these results.

Characteristics and management of patients with stroke and major hemorrhagic episodes with atrial fibrillation under vitamin K antagonist therapy. EVENTHO study

Introduction and objective: In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes.Materials and methodsEVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months.ResultsThe study included 585 patients (median age [range] 82.3 [43.6–96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA2DS2-VASc: 4.3 [4.2–4.4] and HAS-BLED: 2.2 [2.1–2.3]). Poor anticoagulation and VKA maintenance were higher in patients with major hemorrhagic episode (p<0.0001). The most common situations after hospital discharge were: functional dependence, neurological sequelae and death.ConclusionsIn the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode. (AU)

Introducción y objetivo: En España, los antagonistas de la vitamina K (AVK) siguen siendo el tratamiento estándar para la prevención de las complicaciones tromboembólicas y hemorrágicas en pacientes con fibrilación auricular (FA), a pesar del alto riesgo de presentar efectos adversos. El objetivo de este estudio fue caracterizar el perfil de los pacientes tratados con AVK que experimentaron un ictus/embolia sistémica o hemorragia mayor, su evolución y las acciones realizadas tras esos episodios.Materiales y métodosEVENTHO fue un estudio multicéntrico observacional realizado en 22 unidades españolas de anticoagulación. Se incluyó en el estudio a pacientes≥18 años con FA que habían tenido hemorragia mayor (67,8%) o ictus/embolia sistémica (32,1%) durante 2016 y estaban en tratamiento con AVK (acenocumarol [98,2%] o warfarina [1,8%]). El tiempo en rango terapéutico (TRT) se calculó según el método de Rosendaal basado en los valores del índice internacional normalizado de los 6 meses previos.ResultadosEl estudio incluyó a 585 pacientes (edad mediana 82,3 [rango 43,6-96,2] años; 51,1% hombres; CHA2DS2-VASc medio 4,3 [IC 95% 4,2-4,4] y HAS-BLED medio 2,2 [IC 95% 2,1-2,3]). La mala anticoagulación y el mantenimiento de los AVK fueron mayores en los pacientes con hemorragia mayor (p<0,0001). Las situaciones más frecuentes tras el alta hospitalaria fueron: dependencia funcional, secuelas neurológicas y muerte.ConclusionesEn la muestra estudiada, la mitad de los pacientes con FA que tuvieron ictus/embolia sistémica o hemorragia mayor presentaban un TRT inadecuado y, a pesar de ello, tras el alta hospitalaria, reiniciaron el tratamiento con AVK. Estos resultados destacan la necesidad de evaluar alternativas terapéuticas más seguras y eficaces en pacientes con FA con mal control del TRT tras sufrir un ictus/embolia sistémica o hemorragia mayor. (AU)

Duration of Anticoagulation Therapy in Patients with Genetic Inherited Thrombophilia.

Background: Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. Case reports: We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for Prothrombin (PTB G20210A) in the first patient, his brother (the second case) was compound heterozygote for PTB and for MTHFR C677T, and his sister (third case) was heterozygous only for the PTB mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for PTB) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Conclusion: Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.

Warfarin resistance: possibilities to solve this problem. A case report.

Effective prevention of thromboembolism is essential for patients with mechanical prosthetic heart valves. For this group of patients, vitamin K antagonists (VKAs) remain the drug group of choice despite the widespread use of new anticoagulants in other diseases. As a consequence, warfarin resistance remains a serious challenge for physicians. The current report describes a 65-year-old male patient that had a mechanical prosthetic aortic valve implanted due to severe aortic insufficiency after infective endocarditis. Despite consistent increases in his warfarin dose, the level of international normalized ratio (INR) remained very low. The patient was considered to have warfarin resistance. Warfarin was successfully replaced by another VKA, acenocoumarol, which resulted in a stable INR observed over 1 year of follow-up. Achieving the target INR in patients with mechanical prosthetic heart valves using VKAs is the main goal of thromboprophylaxis. Although the genetic changes that cause warfarin resistance are understood, the options to overcome these pharmacogenetic issues remain limited. Based on the success with this current patient, physicians with similar patients with warfarin resistance might wish to consider replacing warfarin with acenocoumarol.

Paciente con incumplimiento terapéutico en situación vulnerable. Intervención coordinada de una farmacia comunitaria y del equipo de atención primaria / Patient with therapeutic non-compliance in a vulnerable situation. Coordinated intervention of a community pharmacy and the primary care team

PRESENTACIÓN DEL CASO / ANTECEDENTES: mujer francesa de 81 años, afincada en Tenerife, que no habla español, Es una paciente polimedicada, tratada con Acenocumarol y Bromazepam, que en la farmacia refiere sufrir frecuentes hemorragias, así como aturdimiento y caídas frecuentes.EVALUACIÓN: la farmacéutica entrevistó a la paciente, detectando la toma de Bromazepam en el desayuno, cuando estaba prescrita en la noche, lo que podría explicar el aturdimiento y las caídas. Se detectó que la paciente no comprendía los símbolos de la pauta de acenocumarol, ni las instrucciones escritas en español por su médico. Su pauta estaba caducada y se comprobó que la paciente no asistía a los controles del índice INR. El incumplimiento en la frecuencia de dichos controles eleva el riesgo de hemorragias, según se describe en la bibliografía.INTERVENCIÓN: en visita presencial en el Centro de Salud, su médico, la farmacéutica y paciente acordaron utilizar Sistemas Personalizados de Dosificación (SPD) y prestar apoyo a la paciente para que asistiera a los controles de INR. Las pautas de acenocumarol se entregaron por parte del médico directamente a la farmacia por correo electrónico.RESULTADO / SEGUIMIENTO: en las primeras semanas se detectó una mejoría del estado general de la paciente. Sin embargo, tres semanas después apareció hemorragia digestiva, infección de orina, confusión y trastorno de conducta. Las hemorragias gastrointestinales constituyen el principal efecto adverso de los anticoagulantes, habiéndose descrito que los sangrados menores aumentan el riesgo de aparición de hemorragias mayores. (AU)

Over-anticoagulation by vitamin K antagonists and gender differences.

BACKGROUND: Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This retrospective study has evaluated a possible association among over-anticoagulation and gender, type and indications to VKAs, TTR and bleeding. Moreover, the decrease of the INR level, after VKAs withdrawal, was considered. METHODS: From December 2020 to January 2004, 1230 patients with venous thromboembolism or atrial fibrillation were enrolled. Age, gender, type of VKAs, clinical indications, INR values and bleeding events were recorded. TTR was calculated considering the entire period of treatment. RESULTS: A total of 1616 and 1759 over-anticoagulation episodes were found in males and females, respectively. The median INR value was 4.5 (4.0-19.04). Thirty-two percent of the patients did not have an overdose throughout the observation period. The median number of over-anticoagulation per year was significantly higher in females (0.39-year) than in males (0.28-year). After 24 h of VKAs withdrawal, INRs were similar in both genders. Logistic regression analysis showed that the episodes of over-anticoagulation per year were associated with females, atrial fibrillation, warfarin therapy, follow-up length longer than 4 years, and TTR <73%, but were not associated to bleeding episodes. CONCLUSION: The higher number of over-anticoagulation can explain the lower TTR in females. An excess of anticoagulation is not associated with bleeding events. The recovery of INR performs better when acenocoumarol is used, therefore, in patients who present several episodes of over-anticoagulation, acenocumarolo could replace warfarin.

A journey through anticoagulant therapies in the treatment of left ventricular thrombus in post-COVID-19 heparin-induced thrombocytopenia: a case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet factor 4 (anti-PF4)/heparin antibodies determine the diagnosis. CASE PRESENTATION: A 57-year-old man who was treated with acenocoumarol due to a chronic left ventricular thrombus was admitted to the hospital for severe SARS-CoV-2 pneumonia and pulmonary embolism. The patient was started on bemiparin and discharged. Left lower limb acute arterial ischemia and thrombocytopenia were diagnosed 18 days later. Computed tomography angiography revealed a large left ventricular thrombus and multiple arterial thrombi. Left femoral-popliteal thromboembolectomy was performed. Anti-PF4/heparin antibodies confirmed an HIT diagnosis. Fondaparinux (7.5 mg/24 h) was initiated, but cardiac surgery was necessary. Bivalirudin was used during surgery, with an initial load (1.25 mg/kg) and maintenance infusion (2.5 mg/kg/h). The cardiac thrombus was extracted, but the patient experienced a postsurgical myocardial infarction. Percutaneous cardiovascular intervention (PCI) required a bivalirudin load (0.75 mg/kg) and maintenance infusion (1.75 mg/kg/h). No coronary lesions were detected, and argatroban was started afterwards (0.5 µg/kg/min). When the platelet count exceeded 100 × 109/L, acenocoumarol was initiated. Thereupon, acetylsalicylic acid (100 mg/24 h) was added. No other complications have been reported to date. CONCLUSION: The clinical presentation of intraventricular and multiple arterial thrombi is remarkable. SARS-CoV-2 infection likely contributed to a hypercoagulable state. The management of patients with HIT undergoing cardiac surgery is challenging. If surgery cannot be delayed, then treatment with bivalirudin is recommended. Additionally, this drug is recommended for PCI. Bivalirudin is safe and well-tolerated in both procedures.

Characteristics and management of patients with stroke and major hemorrhagic episodes with atrial fibrillation under vitamin K antagonist therapy. EVENTHO study.

INTRODUCTION AND OBJECTIVE: In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes. MATERIALS AND METHODS: EVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months. RESULTS: The study included 585 patients (median age [range] 82.3 [43.6-96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA2DS2-VASc: 4.3 [4.2-4.4] and HAS-BLED: 2.2 [2.1-2.3]). Poor anticoagulation and VKA maintenance were higher in patients with major hemorrhagic episode (p<0.0001). The most common situations after hospital discharge were: functional dependence, neurological sequelae and death. CONCLUSIONS: In the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode.

A Brief Review on Determination of Acenocoumarol in Biological and Pharmaceutical Specimens: Analytical Methodologies.

Acenocoumarol is an oral anticoagulant medicinal agent is frequently prescribed for the prophylaxis and the management of thromboembolic events. Acenocoumarol is prescribed in the form of racemic mixture and S- form is a more influential isomer. Acenocoumarol starts quickly with action and absorption, and the effect lasts for 15-20 h. In most patients, the therapeutic prothrombin range is caused 36 h after the primary dose. This review offers a detailed overview of the various analytical methodologies published in the literature from 1976 to uptil now for evaluation acenocoumarol and its combinations in specimens. The present review also stated the chiral analytical methods for the quantification of its enantiomers. A detailed study of the work revealed several analytical methodologies are routinely used for estimation of acenocoumarol includes UV/Vis-Spectrophotometry, liquid chromatography-mass spectrophotometry, high-performance liquid-chromatography, gas chromatography, high-performance thin-layer chromatography, capillary electrophoresis, Fourier-transform infrared spectroscopy and many miscellaneous techniques. Pharmaceutical analysis carried out the prominent task to understand the knowledge of the physicochemical properties of the medicinal agent; since the establishment of a new analytical method is still a challenging task for a research scientist. Thus, the present review will help to research scientist for the development of new analytical methods for the acenocoumarol.

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)

Acenocumarol: uso, adherencia y conocimiento del usuario. Oportunidades para la Atención Farmacéutica / Acenocumarol: use, adherence and knowledge. Opportunities for Pharmaceutical Care

Objetivo: El acenocumarol se mantiene como terapia anticoagulante (TAO) de primera elección. El objetivo de este estudio es valorar y mejorar el conocimiento que sobre el medicamento tienen sus usuarios y favorecer la personalización de la Atención Farmacéutica. Método: 60 pacientes usuarios de acenocumarol de 6 farmacias de Tenerife han participado en una encuesta anónima para valorar el uso, la adherencia y el conocimiento del fármaco. Resultados: 16% de los usuarios desconoce la indicación para la que se les prescribe el anticoagulante, un 32% son pacientes sin adherencia terapéutica y existe un alto grado de desconocimiento (47%) sobre cómo actuar en caso de olvido de una toma. La duplicidad de dosis es un PRM (Problema Relacionado con el Medicamento) real para el 12% de los pacientes. El 87% usa otros tratamientos junto con el acenocumarol (antihipertensivos (24%), antihipercolesterolémicos (11%), ansiolíticos/sedantes (13%) y antiulcerosos (13%)) destacando el uso conjunto de acenocumarol y analgésicos/antiinflamatorios en el 11% de nuestros usuarios de acenocumarol lo que se identifica como un riesgo potencial grave de PRM por interacción. El 35% de los pacientes desconoce las interacciones del acenocumarol, un 70% afirma haber recibido información sobre el fármaco y sólo un 42% de los pacientes manifiesta no haber leído el prospecto. Conclusiones: Se pone de manifiesto la necesidad de mejorar el conocimiento sobre este fármaco por parte del paciente. La intervención farmacéutica mediante la dispensación activa e informada y el seguimiento fármaco terapéutico personalizado permitiría la detección y prevención de PRM durante el uso de acenocumarol.(AU)

Aims: Acenocoumarol remains the first-line anticoagulant therapy (OAT). The objective of this study is to assess and improve the knowledge that users have about this drug and advance in the personalization of pharmaceutical care. Method: 60 acenocoumarol patients from 6 Tenerife pharmacies have participated in an anonymous survey to assess the use, adherence and knowledge of the drug. Results: 16% of acenocoumarol users do not know the indication for which the anticoagulant is prescribed, 32% are patients without therapeutic adherence and there is a high degree of ignorance (47%) about how to act in case of forgetting a dose. Duplication of doses is a real DRP (Drug Related Problem) for 12% of patients. 87% of those surveyed use other treatments together with acenocoumarol (antihypertensive (24%), antihypercholesterolemic (11%), anxiolytic / sedative (13%) and antiulcer (13%)), highlighting the joint use of acenocoumarol and analgesic/anti-inflammatory in 11% of our acenocoumarol users this is identified as a potential serious risk of DRP by interaction. 35% of the patients admit that they are unaware of the possible interactions of acenocoumarol, 70% of the patients affirm that they have received information about the drug, and only 42% of the patients state that they have not read the package leaflet. Conclusions: The need to improve knowledge about this drug by the patient is highlighted. Pharmaceutical intervention through active and informed dispensing and personalized therapeutic drug monitoring would allow the detection and prevention of DRP during the use of acenocoumarol.(AU)

[Switching from acenocoumarol to phenprocoumon: step in personalised anticoagulation?] / Overstappen van acenocoumarol naar fenprocoumon.

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.

Biomodification of acenocoumarol by bifidobacteria.

The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties could be modified. In this context, these studies are relevant for drugs such as acenocoumarol, whose dosage must be controlled due to, among other factors, food-drug interactions. Acenocoumarol is an oral anticoagulant with a narrow therapeutic range. The aim of the present research is to evaluate, in vitro, the effect of bifidobacteria on acenocoumarol. The drug was incubated with Bifidobacterium bifidum CIDCA 5310 or Bifidobacterium adolescentis CIDCA 5317 in MRS broth at 37°C for 24 h in anaerobic conditions. The effect of incubation with sterilized spent culture supernatants (SSCS) was also evaluated. Analysis by RP-HPLC showed that both bifidobacterial strains reduced the area of the acenocoumarol peak and two new peaks were evidenced. In addition, a decrease in the intensity of the bands at 1650, 1390 and 1110/cm was observed in the FTIR spectroscopic determinations. Moreover, a new band appeared at 1720/cm. No effect on the drug was observed when incubation was performed with SSCS. The present study showed a significant change in the concentration of the anticoagulant after incubation with bifidobacteria and results are compatible with biomodification of the drug due to enzymatic activity of bifidobacteria.