Reversing the Tide: A Case of a Mechanical Aortic Valve Recipient Lost to Follow-up, Education on Rivaroxaban Contraindications, and the Vital Role of Acenocoumarol in Preventing Valve Thrombosis.

Aortic stenosis is the most common heart valve disease, especially among the elderly. Symptomatic aortic valve stenosis is linked to a poor prognosis and a high mortality rate if left untreated. The only effective treatment for severe symptomatic aortic stenosis is aortic valve replacement using either a mechanical or a biological prosthesis. Mechanical valve prostheses, while highly durable, are thrombogenic, necessitating lifelong anticoagulation with oral anti-vitamin K agents, such as acenocoumarol. Conversely, bioprosthetic valves, though less durable, carry a minimal thrombogenic risk and do not require anticoagulation. Currently, there is no proven role for direct-acting oral anticoagulants (DOACs) in patients with mechanical heart valves due to insufficient clinical trial data regarding their safety in this patient population. Herein, we present the case of a 59-year-old female known to have aortic stenosis, who underwent surgical treatment with mechanical aortic valve replacement eight years ago. Post-surgery, acenocoumarol was initiated. However, 18 months prior to presenting at our institution, the patient started taking rivaroxaban (a DOAC) instead of acenocoumarol due to the unavailability of acenocoumarol during the ongoing economic crisis in Lebanon, without consulting her cardiologist. Although she was followed up by her general practitioner and reported having a mechanical valve, her son contradicted this, claiming she had a biological valve. After thorough investigations, including chest X-ray, echocardiography, and fluoroscopy, it was confirmed that the patient indeed had a normally functioning mechanical aortic valve. Immediate corrective measures were taken, starting with IV unfractionated heparin and acenocoumarol, targeting an International Normalized Ratio (INR) between 2.5 and 3, while educating the patient about her condition and the importance of adhering to acenocoumarol therapy.

The effect of administering preprocedural VITamin K on the international normalized ratio in patients anticoagulated with ACEnocoumarol (VITKACE-study): a prospective cohort study.

BACKGROUND: The effect of the vitamin K antagonist acenocoumarol on coagulation needs to be reversed when patients undergo an invasive procedure with considerable bleeding risk. A strategy to achieve this is by administering oral vitamin K before a procedure while continuing acenocoumarol. OBJECTIVES: To assess the effect on periprocedural international normalized ratio (INR) values and safety using oral vitamin K as anticoagulant reversal method. METHODS: In this prospective cohort study, consecutive patients using acenocoumarol undergoing elective procedures between 2019 and 2022 were included. According to standard of care in our hospital, patients took 10 mg oral vitamin K 36 to 48 hours before the procedure while continuing their normal use of acenocoumarol. Effectiveness to lower INR to <1.8 preprocedural was assessed. Bleeding and thrombotic complications within 30 days after the procedure were assessed. Periprocedural course of INR was monitored by collecting additional blood samples. RESULTS: Seventy-four patients were included for analysis. On the day of the procedure, an adequate INR of <1.8 was achieved in 99% of patients. One clinically relevant nonmajor bleeding complication and no thrombotic complications were observed during the first 30 days after the procedure. INR gradually restored to therapeutic level during the days after the procedure. CONCLUSION: Using oral vitamin K while patients continue acenocoumarol intake is an effective way to adequately lower INR before an invasive procedure. Low amount of bleeding complications and absence of thromboembolic complications suggest that this is a safe strategy. The INR values returned gradually to therapeutic range after the procedure, probably contributing to the observed low bleeding rate.

Hemolytic Anemia as a Provoking Factor for Recurrent Venous Thromboembolism: A Case Report.

Warm antibody autoimmune hemolytic anemia (WAIHA) is a rare disease that leads to the destruction of red blood cells in the reticuloendothelial system through the mediation of agglutinins (immunoglobulin G (IgG) type in most cases) that attach to the erythrocyte wall at 37 °C. The association of WAIHA and venous thromboembolism (VTE) seems to be higher than other hemolytic disorders classically associated with VTE and there is a current investigation aimed at clarifying this association and establishing some criteria to use anticoagulant treatment in patients with WAIHA. Despite this, WAIHA is a rare cause for the development of recurrent VTE under secondary prophylactic anticoagulant treatment, with only a few cases described in the literature. We present the case of a patient who developed a recurrence of deep vein thrombosis during a WAIHA episode despite treatment with acenocoumarol and a review of the literature.

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)

A Case Series on Acenocoumarol and Linezolid Drug Interaction.

Acenocoumarol is one of the most common drugs used as a part of the management of patients undergoing cardiac surgery. Linezolid, on the other hand, is an antibiotic prescribed post-operatively. Reports of any interaction between the two are very few. Here, we are presenting four case reports of patients admitted to the Cardio Thoracic and Vascular Surgery Department of a tertiary healthcare center in North East India. Drug-drug interactions can lead to long-term and life-threatening effects, and also hamper the management of patients post-operatively. Due to the limited literature, assessing such interactions is difficult. The cases reported here were treated with fresh frozen plasma, and the patients responded well to the treatment and were discharged without further complications.

Clinical value of a tool for managing oral anticoagulation in nonvalvular atrial fibrillation in primary health care. Randomized clinical trial.

INTRODUCTION AND OBJECTIVES: The management of atrial fibrillation is complex and requires improvement at strategic points, such as in the control of patients treated with vitamin K antagonists. The aim of this study was to evaluate the impact on health outcomes of a nonvalvular atrial fibrillation decision support tool based on visualization of the time in therapeutic range in primary care. METHODS: The present randomized clinical trial was conducted in 2018 with a 1-year follow-up in 325 primary care centers in Catalonia. In the intervention centers, the decision support tool was installed to control the time in therapeutic range of patients treated with vitamin K antagonists. The tool was not visualized in the control group. This clinical trial was registered with ClinicalTrials.gov (NCT03367325). RESULTS: In total, 44 556 patients were studied. The intervention protected against admission for stroke (adjusted odds ratio [OR], 0.70; 95% confidence interval [95%CI], 0.55-0.88). The number needed to treat was 3502 (95%CI, 3305-3725) while the number of admissions for stroke avoided was 12.63 (95%CI, 11.88-13.38). The intervention also protected against mortality (adjusted OR, 0.78; 95%CI, 0.67-0.90), with a number needed to treat of 13 687 (95%CI, 10 789-18 714) and number of deaths avoided of 3.23 (95%CI, 2.36-4.10). CONCLUSIONS: The decision support tool was associated with slight reductions in the numbers of admissions for ischemic stroke and mortality. Although the follow-up time was short and the effect of the intervention was small, the results are valuable and could improve implementation of the tool.

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.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

The effect of COVID-19 vaccination on anticoagulation stability in adolescents and young adults using vitamin K antagonists.

INTRODUCTION: The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA) users, COVID-19 vaccination has been associated with an increased risk of supra- and subtherapeutic INRs. Whether this association is also observed in AYAs using VKA is unknown. Our aim was to describe the stability of anticoagulation after COVID-19 vaccination in AYA VKA users. MATERIALS AND METHODS: A case-crossover study was performed in a cohort of AYAs (12-30 years) using VKAs. The most recent INR results before vaccination, the reference period, were compared with the most recent INR after the first and, if applicable, second vaccination. Several sensitivity analyses were performed in which we restricted our analysis to stable patients and patients without interacting events. RESULTS: 101 AYAs were included, with a median age [IQR] of 25 [7] years, of whom 51.5 % were male and 68.3 % used acenocoumarol. We observed a decrease of 20.8 % in INRs within range after the first vaccination, due to an increase of 16.8 % in supratherapeutic INRs. These results were verified in our sensitivity analyses. No differences were observed after the second vaccination compared to before and after the first vaccination. Complications after vaccination occurred less often than before vaccination (9.0 vs 3.0 bleedings) and were non-severe. CONCLUSIONS: the stability of anticoagulation after COVID-19 vaccination was decreased in AYA VKA users. However, the decrease might not be clinically relevant as no increase of complications nor significant dose adjustments were observed.

Spontaneous Iliopsoas Hematoma in a Patient on Acenocoumarol: Report of a Rare Case.

Spontaneous hematoma of the iliopsoas is a rare pathological circumstance; in the majority of cases published in the literature, it is associated with disorders of hemostasis due to anticoagulant treatment or coagulopathies. We present a case of a 64-year-old man on acenocoumarol, an anticoagulant of the vitamin K antagonist family, for atrial fibrillation, who presented with a severe left hip and flank pain with a huge ecchymosis on the left flank and a partial inability to extend the left thigh. A CT scan confirmed the diagnosis of iliopsoas hematoma. Given the hemodynamic stability of the patient, he benefited from a conservative treatment with a favourable evolution. This case highlights the underlying conditions, diagnosis, and treatment of this uncommon complication.

Acenocoumarol-Induced Diffuse Alveolar Hemorrhage: A Case Report.

Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar spaces of the lung. DAH is often associated with systemic autoimmune diseases, coagulation disorders, drugs, inhaled toxins, or transplantation. This study describes a rare case of acenocoumarol-induced DAH, a pulmonary disorder, which has not been reported before. A 48-year-old male presented with a history of rheumatic heart disease with mitral stenosis with moderate mitral regurgitation status post mitral valve replacement. He was taking acenocoumarol but did not keep his prothrombin time-international normalized ratio (PT-INR) monitoring and came to the hospital with complaints of cough, hemoptysis, and breathlessness. Chest x-ray and high-resolution computed tomography (HRCT) thorax were done which revealed diffuse patchy opacities and pulmonary hemorrhage, respectively. After nine days of hospital stay with appropriate management with corticosteroids, antibiotics, and intravenous fluids, the patient was doing well.

Cutaneous Necrosis Over the Nose and Lower Limbs Induced by Acenocoumarol: A Case Report and Literature Review.

Coumarin derivatives are the most used class of oral anticoagulants, and almost 1-2% of adults worldwide take it in the form of warfarin (WA) or acenocoumarol (AC). Cutaneous necrosis is a rare and severe complication of oral anticoagulant therapy. Most commonly, it occurs in the first 10 days, and the incidence peaks between the third and sixth day of starting treatment. Cutaneous necrosis due to AC therapy is underreported in the literature, and studies refer to this condition as "coumarin-induced skin necrosis"; however, this term is not totally accurate, as coumarin itself has no anticoagulant properties. We report a case of a 78-year-old female patient with AC-induced skin necrosis, who presented with cutaneous ecchymosis purpura over her face, arms, and lower extremities 3 hours after AC intake.

[Direct-acting oral anticoagulants in antiphospholipid syndrome: A systematic review]. / Anticoagulantes de acción directa en el síndrome antifosfolípido. Revisión sistemática.

The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid syndrome (APS). We searched for clinical trials, cohort studies and meta-analyses published from January 1, 2012 to September 30, 2022. Articles that analyzed the efficacy of DOAC in the prevention of thrombosis recurrence, with or without comparison with antivitamin K (VKA) drugs, were selected. DOACs, specifically rivaroxaban and apixaban, were significantly less effective than VKAs in preventing recurrence of thrombosis in patients with APS and prior arterial thrombosis or the concomitant presence of two or three different antiphospholipid antibodies. The proportion of patients with severe bleeding as side effect are similar in those treated with DOAC and with VKA. The results argue against the use of DOAC in the treatment of patients with thrombotic APS.

Acenocoumarol, an Anticoagulant Drug, Prevents Melanogenesis in B16F10 Melanoma Cells.

Hyperpigmentation can occur in abnormal skin conditions such as melanomas, as well as in conditions including melasma, freckles, age spots, seborrheic keratosis, and café-au-lait spots (flat brown spots). Thus, there is an increasing need for the development of depigmenting agents. We aimed to repurpose an anticoagulant drug as an effective ingredient against hyperpigmentation and apply cosmeceutical agents. In the present study, the anti-melanogenic effects of two anticoagulant drugs, acenocoumarol and warfarin, were investigated. The results showed that both acenocoumarol and warfarin did not cause any cytotoxicity and resulted in a significant reduction in intracellular tyrosinase activity and melanin content in B16F10 melanoma cells. Additionally, acenocoumarol inhibits the expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, suppressing melanin synthesis through a cAMP-dependent, protein kinase (PKA)-dependent downregulation of microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Furthermore, anti-melanogenic effects were exerted by acenocoumarol through downregulation of the p38 and JNK signaling pathway and upregulation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3ß (GSK-3ß) cascades. In addition, the ß-catenin content in the cell cytoplasm and nucleus was increased by acenocoumarol through a reduction in the phosphorylated ß-catenin (p-ß-catenin content). Finally, we tested the potential of acenocoumarol for topical applications by conducting primary human skin irritation tests. Acenocoumarol did not induce any adverse reactions during these tests. Based on the results, it can be concluded that acenocoumarol regulates melanogenesis through various signaling pathways such as PKA, MAPKs, PI3K/Akt/GSK-3ß, and ß-catenin. These findings suggest that acenocoumarol has the potential to be repurposed as a drug for treating hyperpigmentation symptoms and could provide new insights into the development of therapeutic approaches for hyperpigmentation disorders.

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.

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.

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.

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.

Uso inadecuado del fármaco acenocumarol en la fibrilación auricular no valvular

Introducción: El uso del acenocumarol como anticoagulante, constituye un aporte al tratamiento de la fibrilación auricular no valvular. En la actualidad existen otros tipos de anticoagulantes que no requieren control tan exhaustivo de la prueba digital International Normaizedl Ratio y tienen menos efectos secundarios. España es uno de los pocos países de Europa que continúa indicando acenocumarol, de forma similar a la warfarina. Tanto es así, que a los médicos de atención primaria no se les permite prescribir otros anticoagulantes más eficaces y menos molestos, para el paciente al realizar la prueba digital. Objetivo: Analizar el uso inadecuado del fármaco acenocumarol en la fibrilación auricular no valvular. Métodos: Se realizó un estudio exploratorio, en un sistema de salud de atención primaria y hospitales de categoría secundaria. La población la integraron 2 650 habitantes del sureste español con fibrilación auricular no valvular, tomadores de acenocumarol con seguimiento de 12 meses. Resultados: Se consideró las variaciones y labilidad del valor International Normalized Ratio, entre 2,0-3,0 en determinaciones cada 28 días, no obstante a la enfermedad cardiovascular y cifras obtenidas respecto a las anteriores. El tiempo de seguimiento fue 12 meses y desapareció la fragilidad, se tomaron muestras cada 28 días. Antes de finalizar el estudio, desapareció la labilidad del International Normalized Ratio durante más de tres meses en 53 (97,95 %) de los pacientes. Dado que la mayoría de los enfermos que consumían acenocumarol tenían edades por encima de 65 años y estaban sometidos a régimen de poli medicación, los medicamentos que consumían, fueron motivo de evaluación. Conclusiones: El tiempo transcurrido entre la determinación del International Normaizedl Ratio y la última ingesta de alimentos y medicamentos, no fue correcto, existe tendencia a realizar determinaciones anárquicas del International Normalized Ratio, sin investigaciones relacionadas con fármacos consumidos junto al acenocumarol.

Introduction: The use of acenocoumarol as an anticoagulant represents a contribution to the treatment of non-valvular atrial fibrillation. At present, there are other types of anticoagulants that do not require such exhaustive control of the International Normalized Ratio digital test and have fewer side effects. Spain is one of the few countries in Europe that continues to prescribe acenocoumarol, which is similar to warfarin. So much so that primary care physicians are not allowed to prescribe other more effective and less troublesome anticoagulants for the patient when performing the digital test. Objective: To analyze the inappropriate use of the drug acenocoumarol in non-valvular atrial fibrillation. Methods: An exploratory study was carried out in a primary health care system and secondary category hospitals. The population consisted of 2650 inhabitants of southeastern Spain with non-valvular atrial fibrillation, taking acenocoumarol with 12 months follow-up. Results: We considered the variations and lability of the International Normalized Ratio value, between 2.0-3.0 in determinations every 28 days, regardless of cardiovascular disease and figures obtained in relation to the previous. The follow-up time was 12 months and the lability disappeared, samples were taken every 28 days. Before the end of the study, the lability of the International Normalized Ratio disappeared for more than three months in 53 (97.95%) of the patients. Since most of the patients taking acenocoumarol were over 65 years of age and on polymedication, the medications taken by each of them were evaluated. Conclusions: The time elapsed between the International Normalized Ratio determination and the last intake of food and medication was not correct, and there is a tendency to perform anarchic determinations of the International Normalized Ratio without investigations related to drugs consumed together with acenocoumarol.

Estudio del desempeño analítico del dispositivo portátil microINR en pacientes anticoagulados con acenocumarol / Analytical performance of the microINR portable device in acenocoumarol anticoagulated patients

Resumen La razón internacional normalizada (RIN) se utiliza para controlar a los pacientes anticoagulados con antagonistas de la vitamina K. El objetivo de este estudio fue evaluar el desempeño del nuevo dispositivo portátil microINR, que utiliza tromboplastina recombinante, en pacientes anticoagulados con acenocumarol. Grupo 1: los pacientes proporcionaron muestras de sangre venosa y capilar para realizar pruebas paralelas que permitieron comparar microINR con cinco combinaciones diferentes de reactivo/sistema de detección: tromboplastina de cerebro de conejo con detección nefelométrica, foto-óptica y por viscosidad y tromboplastina humana recombinante con detección nefelométrica y fotoóptica. Todas las tromboplastinas tenían un índice de sensibilidad internacional (ISI) específico de equipo informado por el fabricante menor de 1,10. Grupo 2: los resultados de microINR se compararon con CoaguChek como dispositivo preestablecido. La precisión se evaluó utilizando materiales de control líquidos. El coeficiente de variación del material de control en microINR fue de 6,2%. El análisis de regresión de Passing-Bablok y Bland-Altman mostró un coeficiente de correlación superior a 0,92 y un pequeño sesgo cercano a cero para todas las comparaciones de microINR con cada método tradicional realizado con sangre venosa. Ambos dispositivos portátiles tuvieron un muy buen coeficiente de correlación (r=0,98) y un pequeño sesgo de 0,02. Los resultados muestran un acuerdo clínico del 100% con un grado de concordancia Kappa mayor de 0,63 para todos los métodos tradicionales y de 0,82 para la comparación con Coagu- Chek. De acuerdo a los resultados obtenidos, el microINR es adecuado para el control de pacientes anticoagulados con acenocumarol.

Abstract The international normalised ratio (INR) is used to monitor vitamin K antagonist anticoagulated patients. The aim of this study was to evaluate the performance of the microINR portable device in acenocoumarol anticoagulated patients. Group 1: patients provided capillary and venous blood samples for parallel testing comparing microINR with five different pairs of reagent/clot detection systems: brain rabbit thromboplastin with nephelometric, photooptic and viscocity clot detection and recombinant human thromboplastin with nephelometric and photooptical detection. All thromboplastins have an instrument-specific International Sensitivity Index (ISI) lower than 1.10 reported by the manufacturer. Group 2: microINR results were compared with CoaguChek as an established device. Precision was assessed using liquid control materials. The control material coefficient of variation obtained in microINR device was 6.2%. The Passing-Bablok and Bland-Altman regression analysis showed a correlation coefficient greater than 0.92 and a small bias close to zero for all comparisons of microINR with each traditional coagulation method performed on venous blood samples. Both portable devices had a good correlation (r=0.98) and a very low bias of 0.02. The results show clinical agreement of 100% with a Kappa greater than 0.63 for different traditional INR and greater than 0.83 for CoaguChek. The performance microINR is suitable for the anticoagulation control of patients taking acenocumarol.

Resumo A razão normalizada internacional (INR) é utilizada para monitorar pacientes anticoagulados com antagonistas da vitamina K. O objetivo deste estudo foi avaliar o desempenho do dispositivo portátil microINR, um novo dispositivo que utiliza tromboplastina recombinante, em pacientes anticoagulados com acenocumarol. Grupo 1: os pacientes forneceram amostras de sangue venoso e capilar para testes paralelos que permitiram a comparação do microINR com cinco combinações diferentes de reagente/ sistema de detecção: tromboplastina de cérebro de coelho com detecção nefelométrica, foto-óptica e de viscosidade. Tromboplastina humana recombinante com detecção nefelométrica e foto-óptica. Todas as tromboplastinas tinham o Índice de Sensibilida de Internacional (ISI) específico do kit relatado pelo fabricante inferior a 1,10. Grupo 2: os resultados do microINR foram comparados com o CoaguChek como dispositivo padrão. A precisão foi avaliada usando materiais de controle líquidos. O coeficiente de variação do material de controle em microINR foi de 6,2%. A análise de regressão de Passing-Bablok e Bland-Altman mostrou um coeficiente de correlação maior que 0,92 e um pequeno viés próximo a zero para todas as variáveis. sangue. Ambos os wearables tiveram um coeficiente de correlação muito bom (r=0,98) e um pequeno viés de 0,02. Os resultados mostram 100% de concordância clínica com grau de concordância Kappa maior que 0,63 para todos os métodos tradicionais e 0,82 para a comparação com CoaguChek. De acordo com os resultados obtidos, o microINR é adequado para o controle de pacientes anticoagulados com acenocumarol.