Utility of TTR-INR guided warfarin adjustment protocol to improve time in therapeutic range in patients with atrial fibrillation receiving warfarin.

Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol's implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin.

A Case of Brodifacoum-Induced Epiglottitis.

This case report presents a 33-year-old woman who presented to the emergency department with abdominal pain and gingival and vaginal bleeding. She admitted to using synthetic cannabinoids, and contamination with brodifacoum was suspected, for which qualitative testing was positive. The patient was discharged with an improved international normalized ratio (INR) seven days later with oral vitamin K. Fourteen days after discharge, she re-presented with widespread ecchymosis, leg swelling, and intermittent gingival and vaginal bleeding. Her INR was again elevated. She was controlled with oral vitamin K therapy, stabilized, and discharged three days later. Twenty-eight days following the second discharge, the patient re-presented with oral swelling, right eye ecchymosis, and vaginal bleeding after abstaining from vitamin K therapy for two weeks. A bedside nasopharyngolaryngoscopy showed the base of the tongue, epiglottis, aryepiglottic (AE) folds, arytenoids, and false vocal folds were all edematous with ecchymosis. Due to the diffuse epiglottic and supraglottic edema, the patient was intubated to avoid further decompensation. After receiving IV and oral vitamin K, she was extubated two days later. Her INR fully normalized, and she was then discharged on day 4. Our case of epiglottitis could demonstrate thermal injury associated with smoking synthetic cannabinoids, but given diffuse ecchymosis and severe coagulopathy, hematoma associated with brodifacoum poisoning was considered the most likely etiology. The patient's coagulopathy was rapidly reversed, empiric antibiotic coverage was provided, and she rapidly improved. Brodifacoum exposure has been known to cause increased bleeding, as seen in this case. However, it should also be considered that exposure can lead to epiglottitis. If a similar patient is presented in the future, it is important to consider that coagulopathy may be caused by the adulteration of drugs of abuse, specifically brodifacoum with synthetic cannabinoids.

Evaluation of Citrated Plasma After Thawing for Routine Coagulation Testing.

OBJECTIVE: We aim to find the time in which a thawed citrate plasma sample that was preserved can be analyzed for routine coagulation testing without losing precision. METHODS: Whole blood samples from 30 healthy volunteers were collected in 3.2% sodium citrate vacutainer and centrifuged to separate platelet-poor plasma. Each sample was then aliquoted, one aliquot was used immediately for prothrombin time (PT)-international normalized ratio (INR) and activated partial thromboplastin time (APTT), four were stored at -20°C, and four were stored at -80°C for 24 hours. After 24 hours, the aliquots were taken out and thawed at 37°C in water bath and analyzed after 15, 30, 60, and 120 minutes. STATISTICAL ANALYSIS: Data were presented as mean with standard deviation (SD). Repeated measures ANOVA with Tukey post-hoc test was performed for multiple comparisons. All analysis was done using GraphPAD Prism 8.0 software (GraphPad Software, San Diego, California, USA).  Results: In the case of PT and INR, no statistically significant difference was found between the mean values after thawing for 120 minutes when compared with the mean baseline value. However, the APTT showed a statistically significant difference (p = 0.0232) after 30 minutes of thawing when the sample was stored at -20°C. Furthermore, a statistically significance difference (p = 0.0001) was found after 60 minutes of thawing when the samples were stored at -80°C. CONCLUSION: Plasma samples for the PT and INR may be accepted for assessment up to 120 minutes, when stored at -20°C and -80°C for 24 hours. In the case of APTT, the plasma sample can be used for assessment up to 30 minutes after thawing when stored at -20°C and up to 60 minutes when stored at -80°C.

Elevated INR in a COVID-19 patient after concomitant administration of azvudine and anticoagulants.

Background: Azvudine (FNC) is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). However, drug interactions with azvudine have been poorly studied, especially with no reported cases of azvudine with anticoagulants such as warfarin and rivaroxaban. Case summary: The patient was diagnosed with lower limb venous thrombosis and took warfarin regularly. The international normalized ratio (INR) was stable (2.0-3.0). However, the INR increased to 7.52 after administering azvudine. The patient had no other factors justifying this change. This increase in INR occurred again with the administration of azvudine in combination with rivaroxaban, and the INR increased to 18.91. After azvudine administration was stopped, the INR did not increase when rivaroxaban was used alone. Conclusion: Azvudine, warfarin, and rivaroxaban might have previously unidentified drug interactions that increased the INR. Therefore, the INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

Drug interactions between ALK inhibitors and warfarin with concurrent use of bucolome: a case report.

BACKGROUND: Alectinib, crizotinib, and ceritinib, are anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) that exhibit high protein binding, and their metabolism is associated with the cytochrome P450 (CYP) isoenzymes 2C9 or 3A4. The plasma protein binding rate of warfarin, which is used to prevent and treat venous thromboembolism, is also high. Warfarin is a racemate of S-warfarin and R-warfarin, which are metabolized by CYP2C9 and CYP3A4, respectively. Reports on the drug interactions between each of the above-mentioned ALK-TKIs and warfarin with concurrent use of bucolome are currently lacking. CASE PRESENTATION: We report a case of a patient receiving warfarin and bucolome, whose international normalized ratio (INR) increased after sequential treatment with alectinib, crizotinib, and ceritinib. The patient was a 61-year-old man with a history of aortic valve regurgitation, who was receiving warfarin treatment following aortic valve replacement. Bucolome, which can enhance the effect of warfarin, was also used simultaneously. The patient was diagnosed with primary lung adenocarcinoma, and ALK rearrangement was detected during second-line chemotherapy. After progression of the disease with chemotherapy, sequential treatment with alectinib, crizotinib, and ceritinib was initiated. Pretreatment INR values were in the therapeutic range (target INR of 2-3) but increased to supratherapeutic levels each time after initiation of alectinib, crizotinib, or ceritinib treatment. Adjustment of warfarin dose or discontinuation of bucolome were necessary to maintain the therapeutic INR range. There were no serious bleeding events or substantial changes in dietary intake. Displacement of plasma protein binding or competitive inhibition of metabolism by alectinib, crizotinib, and ceritinib could increase the plasma concentration of the unbound form of warfarin, resulting in high INR values. In addition, alectinib, crizotinib, and ceritinib might cause displacement of bucolome from plasma proteins, followed by displacement of warfarin or inhibition of warfarin metabolism caused by the unbound form of bucolome. CONCLUSIONS: Close monitoring of INR and adjustment of warfarin dosage are needed during treatment with alectinib, crizotinib, or ceritinib in patients who receive warfarin with concurrent use of bucolome.

Serum uric acid level in chronic liver disease and its correlation with Child-Pugh score in a tertiary care hospital from South India.

Background: Chronic liver disease (CLD) is one of the important causes of morbidity and mortality in our country, and since the damage to the liver is irreversible, we have to look for many severity markers or predictors for the prognosis of the patient. In this study, we have tried to correlate the level of serum uric acid (UA) with the severity of CLD presented as a Child-Pugh score. Methods: A cross-sectional observational study was conducted at Vijayanagar Institute of Medical Science (VIMS), Ballari, Karnataka, from October 2015 to June 2017 in the Department of General Medicine. Fifty patients diagnosed with CLD, aged between 18 and 65 years, of either gender, were enrolled in the study. Serum UA levels were measured, and liver function and coagulation parameters were assessed. A statistical analysis was performed to evaluate the association between serum UA levels, liver function test, and coagulation parameters. Results: In our study, the mean serum UA level was 6.52 mg/dl and was raised in patients with CLD in correlation to its severity. Alcoholic liver disease (ALD) was the most common etiology for CLD (80%) followed by hepatitis B (Hep B) virus infection (12%) and hepatitis C (Hep C) virus infection (6%). Serum UA levels increased as the Child-Turcotte-Pugh (CTP) score increased. The mean UA level in CTP class C was 8.29 mg/dl. Various parameters such as serum aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, total bilirubin, international normalized ratio (INR), calcium, and albumin were significantly associated with serum UA levels in CLD patients. Conclusion: The correlation between rising blood UA levels and the Child-Pugh score shows that UA estimate may be a valid and affordable indicator for assessing the extent of liver cirrhosis in CLD.

Rosendaal linear interpolation method appraising of time in therapeutic range in patients with 12-week follow-up interval after mechanical heart valve replacement.

Background: The objective of this study was to evaluate the quality of anticoagulation by the time in therapeutic range (TTR) for patients with 12-week INR follow-up interval. Materials and methods: From January 2018 to December 2020, a selective group of patients who underwent mechanical valve replacement and followed up at our anticoagulation clinic for adjustment of warfarin dose were enrolled. The incidences of complications of anticoagulation therapy were reported by linearized rates. TTR was calculated by the Rosendaal linear interpolation method. Results: Two hundred and seventy-four patients were eligible for this study. The mean age of these patients was 52.8 ± 12.7 years, and 65.7% (180 cases) of them were females. The mean duration of warfarin therapy was 16.7 ± 28.1 months. A total of 1309 INR values were collected, representing 66789 patient days. In this study, the mean TTR was 63.7% ± 18.6%, weekly doses of warfarin were 20.6 ± 6.0 mg/weekly, and the mean monitoring interval for the patient was 53.6 ± 27.1 days. There were 153 cases in good TTR group (TTR ≥ 60%) and 121 cases in poor TTR group (TTR < 60%). The calculated mean TTR in both groups was 42.6% ± 22.1% and 74.8% ± 10.4%, respectively. Compared with the TTR ≥ 60% group, the TTR < 60% group exhibited a more prevalence of female gender (p = 0.001), atrial fibrillation (p < 0.001), NYHA ≥ III (p < 0.001), and lower preoperative left ventricular ejection fraction (LVEF, p = 0.032). In multivariate analysis, female gender (p = 0.023) and atrial fibrillation (p = 0.011) were associated with TTR < 60%. The incidence of major bleeding and thromboembolic events was 2.7% and 1.1% patient-years, respectively. There was one death which resulted from cerebral hemorrhage. The incidence of death was 0.5% patient-years. The difference in anticoagulation-related complications between the TTR < 60% group and the TTR ≥ 60% group was not statistically significant. Conclusion: For patients with stable international normalized ratio monitoring results who are follow-up at anticoagulation clinics, a 12-week monitoring interval has an acceptable quality of anticoagulation. The female gender and atrial fibrillation were associated with TTR < 60%.

Reversal of Oral Vitamin K Antagonists Using Prothrombin Complex Concentration Prior to IV tPA Administration.

Herein, we report two acute ischemic stroke cases that we used prothrombin complex to reverse the effects of warfarin in order to apply intravenous thrombolytic treatment. To the best of our knowledge, there are only limited amount of cases that prothrombin complex concentrates were applied prior to intravenous thrombolytic treatment administration. As one of the biggest acute stroke clinics in our country, we aim to open a discussion for this treatment to be fully researched and understood.

Comparison of capillary and venous blood sampling for routine coagulation assays.

OBJECTIVES: Capillary blood samples are generally assumed as unsuitable for coagulation testing since it is recognized that contamination with tissue factor and dilution with tissue fluid affects the coagulation assay. However, limited data is available about coagulations assays in which capillary blood sampling is compared to the standard venous blood withdrawal method. The aim of this study was to perform a method comparison between capillary and venous blood sampling for routine coagulation assays. METHODS: Both venous and capillary (finger stick) blood samples were collected from 188 healthy volunteers and patients. In citrate plasma, International Normalized Ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, and D-dimer were measured according to routine protocols using the ACL-TOP 750 LAS (Werfen) coagulation analyzer. Regression analysis was performed and the mean relative difference between capillary and venous sampling was reflected to the total allowable error (TEa). RESULTS: Strong correlations and acceptable variations, using the TEa as decision limit, were found for INR, PT, TT, fibrinogen, and D-dimer between capillary and venous sampling. However, capillary sampling resulted in significant shorter APTT values when using the standard APTT-SP Liquid reagent with a mean bias of -10.4% [95% CI -12.4 to -8.4]. CONCLUSION: Based on these results, capillary blood sampling proved to be an alternative blood withdrawal method for routine coagulation assays, with the exception of APTT, if a venipuncture is unavailable or undesired.

Warfarin Dose Requirements in Adults Hospitalized With COVID-19 Infection: A Retrospective Case Series.

PURPOSE: To describe the impact of hospitalization with COVID-19 infection on warfarin dose requirements in adult inpatients. SUMMARY: A retrospective chart review of 8 adults on warfarin admitted to Michigan Medicine with COVID-19 infection was conducted and reported as a case series. Outcomes of interest were difference in average daily dose of warfarin prior to admission (PTA) and while inpatient (IP), warfarin sensitivity, time in therapeutic range (TTR), confirmed or suspected thromboembolic event, any major or clinically significant bleeding episodes, and in-hospital mortality. IP average daily warfarin doses were lower when compared to PTA average daily doses [1.3 mg (1.3) vs. 6.2 mg (4.1)]. The mean percentage decrease in dose was 68.8% (23) and the mean absolute dose difference was 4.8 mg (4.3). Mean IP percentage tests in range was 30.8% (24.6) and mean IP warfarin sensitivity was 4.2 (3.8), both of which differed from PTA TTR and warfarin sensitivity for those with data available (n = 3, n = 6, respectively). One patient was treated for suspected acute pulmonary embolism while on warfarin and one patient experienced clinically relevant bleeding. In-hospital mortality was zero, mean length of stay (LOS) was 17 days (14.4), and mean intensive care unit (ICU) LOS for the 3 patients requiring ICU level care was 14.3 days (4.5). CONCLUSION: Decreased warfarin dose requirements were evident in this group of adults hospitalized with COVID-19 infection. These findings suggest lower doses of warfarin may be needed to achieve therapeutic anticoagulation while inpatient.

Elevated INR in a COVID-19 patient after concomitant administration of favipiravir and warfarin: A case report.

WHAT IS KNOWN AND OBJECTIVE: Favipiravir is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). Warfarin has many drug interactions, but no interactions with favipiravir have been reported. CASE SUMMARY: Our patient was taking warfarin for deep vein thrombosis. The international normalized ratio (INR) was stable (1.65 to 2.0); however, it increased to 4.63 after administering favipiravir. The patient had no other factors justifying this change. WHAT IS NEW AND CONCLUSION: Favipiravir and warfarin might have previously unidentified drug interactions that elevated the INR. Therefore, INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

Increased INR Values Predict Accelerating Deterioration and High Short-Term Mortality Among Patients Hospitalized With Cirrhosis or Advanced Fibrosis.

Background and Objective: An increase in the international normalized ratio (INR) is associated with increased mortality in patients with cirrhosis and other chronic liver diseases, while little is known about the quantitative relationship. This study aimed to investigate the quantitative relationship between the INR and short-term prognosis among patients hospitalized with cirrhosis or advanced fibrosis and to evaluate the role of the INR as a risk factor for short-term liver transplant (LT)-free mortality in these patients. Patients and Methods: This study prospectively analyzed multicenter cohorts established by the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study. Cox regression was used to describe the relationship between the INR and independent risk factors for short-term LT-free mortality. Forest plots were used in the subgroup analysis. Generalized additive models (GAMs) and splines were used to illustrate the quantitative curve relationship between the INR and the outcome and inflection point on the curve. Results: A total of 2,567 patients with cirrhosis and 924 patients with advanced fibrosis were included in the study. The 90-day LT-free mortality of patients with cirrhosis and advanced fibrosis was 16.7% (428/2,567) and 7.5% (69/924), respectively. In the multivariable Cox regression analysis, the increase in the INR was independently associated with the risk of 90-day LT-free mortality both in patients with cirrhosis (HR, 1.06; 95% CI, 1.04-1.07, p < 0.001) and in patients with advanced fibrosis (HR, 1.09; 95% CI, 1.06-1.12, p < 0.001). An INR of 1.6/1.7 was found to be the starting point of coagulation dysfunction with a rapid increase in mortality in patients with cirrhosis or in patients with advanced fibrosis, respectively. A 28-day LT-free mortality of 15% was associated with an INR value of 2.1 in both cirrhosis and advanced fibrosis patients. Conclusions: This study was the first to quantitatively describe the relationship between the INR and short-term LT-free mortality in patients with cirrhosis or advanced fibrosis. The starting points of INR indicating the rapid increase in mortality and the unified cutoff value of coagulation failure in cirrhosis and advanced fibrosis, will help clinicians accurately recognize early disease deterioration.

Tele-pharmacy Anticoagulation Clinic During COVID-19 Pandemic: Patient Outcomes.

Introduction: It is well-established that clinical pharmacist-managed anticoagulation services achieve superior anticoagulation control, with a positive impact. At King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia, the structure of anticoagulation management is a pharmacist-managed specialty service. With the current COVID-19 situation, measures were taken to assure the continuity of patient care by establishing tele-pharmacy anticoagulation clinics. Materials and Methods: This was a prospective study with patients prescribed anticoagulation and followed up for 3 months. Since establishing the anticoagulation virtual clinic in March 2020, 270 patients were recruited in the study. The data collected included age, gender, comorbidities, indication for anticoagulation, intended duration of treatment, warfarin dose, testing of International Normalized Ratio (INR), INR target, range of INR values, time INR that was within the therapeutic range (TTR), and complications of therapy (bleeding and/or bruises). The patients were asked to complete the pharmacist satisfaction survey (PSS) after their consultation to assess patient satisfaction with the new virtual consultation system. Linguistic and cultural validation was conducted for the questionnaire. Results: A total of 270 patients were included in the study. The mean percentage of overall INR values in the range was 59.39% ± 32.84, and the mean time with the overall INR was within the therapeutic range 57.81% ± 32.08. Thirty-one percent of the sample had good anticoagulation control (time in therapeutic range >70%). The median satisfaction score was 32 (IQR 28-36) with a maximum score of 40. Conclusion: This is the first study to assess the tele-pharmacy anticoagulation clinic's efficiency and patient satisfaction in Saudi Arabia during the COVID-19 pandemic. This type of consultation was as effective as face-to-face consultations. The study also highlighted that though the reduction in the cost of care was not substantial, there was a significant increase in resource (clinical pharmacist) utilization as a result of this model. The adoption of tele-pharmacy resulted in time savings for the clinical pharmacists who can be utilized in many other improvement projects in adult ambulatory clinics to ensure the delivery of better quality and safe patient care.

Intoxicación por rodenticidas (raticidas) con superwarfarinas efecto anticoagulante altamente prolongado

Joven de 19 años que realiza intento de suicido en febrero de 2019, ingiriendo 04 bolsas de raticida "Klerat". Llevado a Emergencia en la ciudad de Tarapoto (Región San Martín); le realizan lavado gástrico; recibe Fitomenadiona 2 dosis y lo envían a su casa. A los 11 días post- intoxicación presenta dolores osteomusculares, orina de color rojizo, se añade sangrado por las encías, epistaxis, hematomas, aumenta la gingivorragia y sensación de desvanecimiento; es llevado al Hospital de Yurimaguas. En los exámenes de laboratorio se encuentra: INR:9.7 y alteraciones en el Tiempo de Protrombina (TP):45 y Tiempo de Tromboplastina Parcial activada (TTPA): 60. Recibe tratamiento con Fitomenadiona y Ácido tranexámico. Por persistir gingivorragia escasa y alteraciones en la coagulación se hace la referencia al hospital Nacional Dos de Mayo de la ciudad de Lima. Donde se encuentra: INR: 11.5, TP:120 seg. TTPA: 86.5, Hb:12.2 Leucocitos:10.090 Plaquetas: 320.000, Orina: hematíes 5xc. Leucocitos:0-1 x c. Perfil hepático: Normal, Perfil lipídico: Normal, Rx. de Tórax. Normal, Dímero D: 0.14. Se realizan Pruebas de autoinmunidad, encontrando el Anticoagulante Lúpico: Positivo, siendo el resto de pruebas negativas. Se dio Tto. con Plasma Fresco congelado, crioprecipitados y Fitomenadiona. El examen de orina en CICOTOX encontró metabolitos de hidroxicumarinas POSITIVO. Estuvo hospitalizado por 2 meses, se logra la estabilización en el perfil de coagulación y el INR; dependientes del Tto. con Fitomenadiona. El control de orina en CICOTOX dio negativo a los 2 meses. El control del anticoagulante Lúpico a los 3 meses dio Positivo; a los 6 meses dio Negativo. Tuvo que continuar con Tto. de Fitomenadiona por 10 meses más (dic. 2019), hasta lograr la estabilización total del perfil de coagulación y el INR. Para darle el Alta.

Evolving Paradigm of Prothrombin Time Diagnostics with Its Growing Clinical Relevance towards Cardio-Compromised and COVID-19 Affected Population.

Prothrombin time (PT) is a significant coagulation (hemostasis) biomarker used to diagnose several thromboembolic and hemorrhagic complications based on its direct correlation with the physiological blood clotting time. Among the entire set of PT dependents, candidates with cardiovascular ailments are the major set of the population requiring lifelong anticoagulation therapy and supervised PT administration. Additionally, the increasing incidence of COVID affected by complications in coagulation dynamics has been strikingly evident. Prolonged PT along with sepsis-induced coagulopathy (SIC score > 3) has been found to be very common in critical COVID or CAC-affected cases. Considering the growing significance of an efficient point-of-care PT assaying platform to counter the increasing fatalities associated with cardio-compromised and coagulation aberrations propping up from CAC cases, the following review discusses the evolution of lab-based PT to point of care (PoC) PT assays. Recent advances in the field of PoC PT devices utilizing optics, acoustics, and mechanical and electrochemical methods in microsensors to detect blood coagulation are further elaborated. Thus, the following review holistically aims to motivate the future PT assay designers/researchers by detailing the relevance of PT and associated protocols for cardio compromised and COVID affected along with the intricacies of previously engineered PoC PT diagnostics.

Capecitabine and Warfarin Interaction: A Case Report With Review of Literature and Management Options.

Capecitabine is an orally active prodrug of 5-fluorouracil with improved safety and efficacy that is extensively used as an antineoplastic agent. It is converted to 5-Fluorouracil in the liver and tumor tissues. In vitro assays did not reveal any significant potential for interaction between capecitabine and its metabolites with warfarin. However, several reports provided clinical evidence of such interaction resulting in an elevated international normalized ratio (INR) and bleeding. Here, we report another case of capecitabine and warfarin concurrent administration that resulted in sub- or supra- therapeutic INR without any bleeding episode or venous-thromboembolic event through the follow-up period. Moreover, a review of available management options is also presented in this paper.

Nonalcoholic fatty liver disease impacts the control of the international normalized ratio in patients with atrial fibrillation.

BACKGROUND: It is unclear whether the therapeutic effect of warfarin in patients with atrial fibrillation (AF) and normal liver function differs between those with and without nonalcoholic fatty liver disease (NAFLD). With this in mind, we aimed to evaluate the impact of NAFLD on the international normalized ratio (INR) control in warfarin-treated AF patients with normal liver function. METHODS: We enrolled 600 AF patients aged 28-94 (median 68) with normal liver function who were receiving daily warfarin therapy, 172 with NAFLD and 428 without. The INR and INR/warfarin dosage rate were measured. Four nested multivariable linear regression models adjusted for potential confounders were used to assess whether there were differences in INR and INR/warfarin dose rate between patients with and without NAFLD. RESULTS: The INR, the percentage of patients with INR within the target range of 2.0-3.0, and the INR/warfarin dose rate were lower in patients with NAFLD than those without. In the maximally adjusted multivariable linear regression models, the INR in NAFLD patients (0.22±0.07, P=0.003) was lower than in non-NAFLD patients, and the INR/warfarin dose rate was slightly lower (0.09±0.06, P=0.10) in NAFLD than in non-NAFLD patients. CONCLUSIONS: Our findings suggest that among AF patients, the therapeutic effect of warfarin is impaired in patients who have NAFLD. Therefore, a slightly higher or personally optimized dosage of warfarin might be necessary among AF patients with NAFLD in order to achieve the INR target range.

[Argentine Consensus in effective management of anticoagulation clinics for the use of vitamin k antagonists]. / Consenso Argentino en gestión efectiva de clínicas de anticoagulación para el uso de antagonistas de la vitamina k.

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

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

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

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

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