scholarly journals Unexpected acute pulmonary embolism in an old COVID-19 patient with warfarin overdose: a case report

2021 ◽  
Vol 5 (6) ◽  
Author(s):  
Maxime Coutrot ◽  
Maxime Delrue ◽  
Bérangère S Joly ◽  
Virginie Siguret
Keyword(s):  
Pulmonary Embolism ◽  
Case Report ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Heparin Therapy ◽  
High Incidence ◽  
Severe Epistaxis ◽  
Repeated Administrations ◽  
Concurrent Medication

Abstract Background Severe acute respiratory syndrome coronavirus 2 disease is strongly associated with a high incidence of thrombotic events. Anticoagulation could be a cornerstone in successfully managing severe forms of coronavirus disease 2019 (COVID-19). However, optimal anticoagulant dosing in elderly patients is challenging because of high risk of both thrombosis and bleeding. Case summary We present here the case of an 89-year-old patient receiving warfarin for atrial fibrillation and valvular heart disease, admitted to the intensive care unit for respiratory failure due to COVID-19. The patient presented with a severe epistaxis associated with warfarin overdose [international normalized ratio (INR) > 10]. After a successful initial reversal using vitamin K per os, INR values greatly fluctuated up to 10, requiring repeated administrations of vitamin K. Despite starting low-molecular-weight heparin therapy at therapeutic dose as soon as INR value was below 2.0, the patient further developed an acute bilateral and proximal pulmonary embolism concomitantly with a sharp D-dimer increase. The combination of azithromycin intake, a known inhibitor of CYP2C9, with the presence of CYP2C9*2 and −1639G>A VKORC1, two variants associated with warfarin hypersensitivity, have likely contributed to explain the warfarin overdose and the difficulty to reverse warfarin effect in this patient. Discussion This case report illustrates the complexity of COVID-19 pathophysiology and its management for physicians, especially in patients receiving vitamin K antagonists (VKAs). Infection, concurrent medication use, and pharmacogenetic factors involved in VKA metabolism and pharmacodynamics may lead to a loss of control of anticoagulation. Pulmonary embolism should still be considered in COVID-19 patients even with effective or overdosed anticoagulant therapy.

scholarly journals Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

2016 ◽  
Vol 174 (4) ◽  
pp. 610-623 ◽  
Author(s):  
David A. Fitzmaurice ◽  
Gabriele Accetta ◽  
Sylvia Haas ◽  
Gloria Kayani ◽  
Hector Lucas Luciardi ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio

scholarly journals The international normalized ratio (INR) as seen in a population of patients with atrial fibrillation and cerebral infarction undergoing long-term treatment with vitamin K antagonists

2015 ◽  
Vol 28 (4) ◽  
pp. 269-272
Author(s):  
Anna Szczepańska-Szerej ◽  
Magdalena Wojtan ◽  
Beata Szajnoga
Keyword(s):  
Atrial Fibrillation ◽  
Cerebral Infarction ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Blood Parameters ◽  
Term Treatment ◽  
Adequate Treatment ◽  
Long Term Treatment

Abstract It is estimated that nearly 20% of all cerebral infarctions in the total population are the result of a complication of atrial fibrillation (AF). While oral anticoagulation with vitamin K antagonists (AVKs) substantially reduces this risk, this requires regular monitoring of the international normalized ratio (INR) in order to achieve therapeutic levels (2,0-3,0). The aim of this study was to evaluate a group at high risk of cerebral infarction, among patients with AF undergoing long-term treatment with VKAs, taking into account the significance of therapeutic INR values. The analysed group consisted of 90 acute ischaemic stroke patients with paroxysmal or chronic “non-valvular” AF, receiving treatment with VKAs. As a result of the study, therapeutic INR values (≥ 2) were seen in thirty-five of these individuals (38,8%), while 55 (61,2%) showed non-therapeutic INR values. Moreover, there were no differences in demographics, vascular risk factors, biochemical and morphological blood parameters, mean CHA2DS2-VASc score and TOAST classification between either of the two groups. Furthermore, no additional factor that would increase their risk of cerebral infarction during the adequate treatment with VKAs was found. However, patients with non-therapeutic INR values had a statistically significantly higher frequency of concomitant moderate pathology of the bicuspid valve, p<0.05. Hence, a lack of proper control of INR can proved to be particularly dangerous for this subgroup of patients. Hence, this is a group with an elevated risk of cerebral infarction and therefore requires special oversight of VKA treatment or NOA treatment.

Management of pulmonary embolism in patients with cancer

ESC CardioMed ◽  
2018 ◽  
pp. 2790-2794
Author(s):  
Cihan Ay ◽  
Florian Posch
Keyword(s):  
Pulmonary Embolism ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Standard Of Care ◽  
Current Standard ◽  
Patients With Cancer ◽  
High Index Of Suspicion ◽  
Excessive Anticoagulation

Pulmonary embolism (PE) is a frequent complication in patients with cancer. Clinicians have to maintain a high index of suspicion to reduce the large proportion of PEs that remain undiagnosed in the cancer population. Thrombolysis is not a standard treatment for haemodynamically unstable patients with cancer-associated PE because the risk of haemorrhage can be excessive. Anticoagulation with a low-molecular-weight heparin (LMWH) for at least 6 months is the current standard of care for the treatment of cancer-associated PE, while vitamin K antagonists are a reasonable second choice for patients with contraindications against LMWH or a strong preference towards an oral agent. Although an indirect network meta-analysis suggests that non-vitamin K-dependent oral anticoagulants may be comparably efficacious and safe as LMWH for treating PE in cancer patients, these agents cannot be recommended as a standard first-line treatment at this time because a head-to-head comparison to the standard of care has not yet been reported. Anticoagulation beyond 6 months is an emerging concept; however, the patient population that may benefit from this intervention still needs to be defined. Guidance statements facilitate the management of challenging patients with brain metastases, unsuspected PE, thrombocytopenia, and recurrent PE.

scholarly journals New artificial intelligence prediction model using serial prothrombin time international normalized ratio measurements in atrial fibrillation patients on vitamin K antagonists: GARFIELD-AF

2019 ◽  
Vol 6 (5) ◽  
pp. 301-309 ◽  
Author(s):  
Shinichi Goto ◽  
Shinya Goto ◽  
Karen S Pieper ◽  
Jean-Pierre Bassand ◽  
Alan John Camm ◽  
...  
Keyword(s):  
Neural Network ◽  
Artificial Intelligence ◽  
Atrial Fibrillation ◽  
Prothrombin Time ◽  
Clinical Outcomes ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
One Dimensional ◽  
Major Bleed

Abstract Aims Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment. Methods and results Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0–30 after starting treatment and clinical outcomes over days 31–365 in a derivation cohort (cohorts 1–3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4–5; n = 1523). The model’s c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively. Conclusions Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes.

Guidelines for certification of International Normalized Ratio (INR) for vitamin K antagonists monitoring according to the EN ISO 22870 standards

2018 ◽  
Vol 76 (3) ◽  
pp. 271-299
Author(s):  
Marie Brionne-François ◽  
Anne Bauters ◽  
Christine Mouton ◽  
Sophie Voisin ◽  
Claire Flaujac ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio

scholarly journals Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 861-867 ◽  
Author(s):  
Caroline Moreau ◽  
Fanny Bajolle ◽  
Virginie Siguret ◽  
Dominique Lasne ◽  
Jean-Louis Golmard ◽  
...  
Keyword(s):  
Vitamin K ◽  
Dose Response ◽  
Maintenance Dose ◽  
Vitamin K Antagonists ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Individual Variability ◽  
Dose Requirement ◽  
Warfarin Dose Requirement ◽  
Main Determinants

Abstract Managing vitamin K antagonist (VKA) therapy is challenging in children because of a narrow therapeutic range and wide inter- and intra-individual variability in dose response. Only a few small studies have investigated the effect of nongenetic and genetic factors on the dose response to VKAs in children. In a cohort study including 118 children (median age 9 years; range, 3 months-18 years) mostly with cardiac disease, we evaluated by multivariate analysis the relative contribution of nongenetic factors and VKORC1/CYP2C9/CYP4F2 genotypes on warfarin (n = 83) or fluindione (n = 35) maintenance dose and the influence of these factors on the time spent within/above/below the range. The results showed that height, target international normalized ratio and VKORC1 and CYP2C9 genotypes were the main determinants of warfarin dose requirement, accounting for 48.1%, 4.4%, 18.2%, and 2.0% of variability, respectively, and explaining 69.7% of the variability. Our model predicted the warfarin dose within 7 mg/wk in 86.7% of patients. None of the covariates was associated with the time spent above or below the international normalized ratio range. Whether this model predicts accurately the effective maintenance dose is currently being investigated.

Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism

2003 ◽  
Vol 89 (06) ◽  
pp. 953-958 ◽  
Author(s):  
Joshua Beckman ◽  
Kelly Dunn ◽  
Arthur Sasahara ◽  
Samuel Goldhaber
Keyword(s):  
Pulmonary Embolism ◽  
Unfractionated Heparin ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Standard Therapy ◽  
Vitamin K Antagonists ◽  
Hospital Length Of Stay ◽  
Hemorrhagic Complication ◽  
Oral Vitamin ◽  
Symptomatic Pulmonary Embolism

SummaryConventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a “bridge” to oral anticoagulation. This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect. Oral vitamin K antagonists require frequent blood testing to optimize dosing, and their interactions with other medications and foods make regulation difficult. Therefore we tested a different approach to therapy: long-term enoxaparin monotherapy.We randomized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin (N=40) or to intravenous unfractionated heparin as a “bridge” to warfarin, target INR 2.0-3.0 (N=20). Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by randomized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily.In an intention-to-treat analysis, 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 standard therapy patients (p = 0.54). One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 standard therapy patients (p = 0.26). Median hospital length of stay was shorter with enoxaparin compared to standard therapy (4 vs. 6 days) (p = 0.001). Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic, acute pulmonary embolism is feasible and warrants further study in a large clinical trial.

From Vitamin K Antagonists to Liver International Normalized Ratio: A Historical Journey and Critical Perspective

2014 ◽  
Vol 40 (08) ◽  
pp. 845-851 ◽  
Author(s):  
Alexander Gatt ◽  
Dong Chen ◽  
Rajiv Pruthi ◽  
Patrick Kamath ◽  
Michael Leise ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Critical Perspective

scholarly journals Effectivity of a joint didactic intervention by School for Patients on inappropriate control prothrombin time anticoagulated patients. Protocol for developing a randomized and controlled clinical trial.

2020 ◽  
Author(s):  
Leovigildo Ginel-Mendoza ◽  
Alfonso Hidalgo Hidalgo-Natera ◽  
Rocio Reina-Gonzalez ◽  
Rafael Poyato-Ramos ◽  
Inmaculada Lupianez-Perez ◽  
...  
Keyword(s):  
Social Support ◽  
Clinical Trial ◽  
Prothrombin Time ◽  
Vitamin K ◽  
Oral Anticoagulant ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Control Group ◽  
Therapeutic Level ◽  
Anticoagulated Patients

Abstract Background Oral anticoagulant drugs represent an essential tool in thrombo-embolic events prevention. Most used are vitamin K antagonists, whose plasma level is monitored by measuring prothrombin time using the International Normalized Ratio. If it takes values out of the recommended range, the patient will have a higher risk of suffering from thromboembolic or hemorrhagic complications. Previous research has shown that about 33% of total patients keep values on inappropriate level. The purpose of the study is to improve International Normalized Ratio control figures by a joint didactic intervention based on the Junta de Andalucía School for Patients method that will be implemented by anticoagulated patients themselves. Methods A randomized clinical trial was carried out at primary care centers from one healthcare area in Málaga (Andalusia, Spain). Study population: patients included in an oral anticoagulant therapy program consisting in using vitamin K antagonists. First step detection of patients on oral anticoagulation program with International Normalized Ratio control on therapeutic level during 65% or less over total time. Second step: patients with inappropriate International Normalized Ratio control were included in two groups: Group 1 or Joint Intervention Group: patients were instructed a joint didactic intervention “from peer to peer”, by a previously trained and expert anticoagulated patient. Group 2 or Control Group: Control group performed usual clinical practice: people were schedule by nurses about one time per month, except cases in which controls were inappropriate; in those circumstances patients were schedule before that period expired. In order to built the study group and the control group, 312 individuals were required (156 in each group) to detect differences in INR figures equal or higher than 15% between both groups. Study variables time on therapeutic levels before and after intervention, sociodemographic variables, vital signs, existence of cardiovascular risk factors or accompanying diseases in the clinical records, laboratory test including complete blood count, bleeding time, and prothrombin time or partial thromboplastin time and blood chemistry, other prescribed drugs, and social support. Almost-experimental analytic study with before-after statistical analysis of the intervention were made. Lineal regression models were applied on main variables results (International Normalized Ratio value, time on therapeutic level) inputting sociodemographic variables, accompanying diseases and social support.

Sign in / Sign up

Export Citation Format

Share Document