Telemedicine-based medical care compared to in-person medical care for warfarin follow-up: A retrospective propensity score matching cohort study.

PURPOSE: Telemedicine is underutilized in Saudi Arabia, which is a matter of concern, especially since previous literature has showed its equivalence with office visits in providing access to care and convenience for patients while reducing anticoagulation-related bleeding events when appropriate measures are followed. The purpose of this study is to analyze the efficacy of telehealth-based care compared to in-person visit care for warfarin follow-up. METHODS: The authors conducted a retrospective chart review comparing the mean percentage of time in the therapeutic range (TTR) of international normalized ratio (INR) values among patients prescribed warfarin from July 2019 to November 2020 at King Faisal Specialist Hospital & Research Center - Jeddah Branch whose anticoagulant therapy was managed via telemedicine or through in-person clinic visits. A subcohort analysis of outcomes in the telemedicine and in-person groups was performed using propensity score matching, and descriptive analysis was done for the entire cohort. RESULTS: A total of 350 patient records were included in this retrospective study. Matched analysis for 148 patients using propensity score matching showed that the mean (SD) percentages of TTR were 62.82% (19.46%) and 70.61% (19.83%) in the telemedicine and in-person groups, respectively (P = 0.017). There was no statistical difference in the incidence of major or minor bleeding events, thromboembolic events, and hospital readmission between the two groups. CONCLUSION: The study results showed that patients on oral anticoagulation therapy managed through a telemedicine method had a lower overall TTR percentage than a matched group of patients managed through in-person anticoagulant clinic visits, thus demonstrating that using a telemedicine approach alone for warfarin follow-up may not help patients to maintain their INR target level.

Outcomes of Warfarin Home INR Monitoring vs Office-Based Monitoring: a Retrospective Claims-Based Analysis.

BACKGROUND: Home INR testing (patient self-testing) is feasible and effective for warfarin patients but little is known about real-world differences in outcomes for patients using PST versus laboratory-based INR monitoring. OBJECTIVE: To compare the safety/efficacy of patient self-testing of real-world warfarin therapy versus office/lab-based monitoring of therapy. DESIGN/SETTING/PARTICIPANTS/EXPOSURE: A retrospective claims-based analysis of warfarin patients enrolled in the MarketScan® Commercial Claims and Encounters and Medicare databases between January 1, 2013, and March 30, 2020. Stratification was based on INR testing method: patient self-testing versus testing at physicians' offices/local laboratory. The probability of adverse events in each cohort was determined after adjusting for demographic and baseline clinical characteristics using a repeated measures analysis. MAIN MEASURES: Rates of all adverse events: deep venous thrombosis, pulmonary embolism, bleeding, and stroke. A secondary outcome of interest was emergency department visits. KEY RESULTS: A total of 37,837 patients were included in the analysis: 1592 patients in the patient self-testing group and 36,245 in the office-based therapy group. After adjusting for demographic and baseline clinical characteristics, patients in the office-based group had statistically significantly higher rates of all adverse events (incidence rate ratio [IRR]=2.07, 95% CI [1.82, 2.36]), and specific adverse events including thromboembolism (IRR=4.38, 95% CI [3.29, 5.84]), major bleed (IRR=1.45, 95% CI [1.28, 1.64]), and stroke (IRR=1.30, 95% CI [1.05, 1.61]) than patients in the patient self-testing group. Office-based patients also had a statistically significant higher rate of emergency department visits than patient self-testing patients (IRR = 1.65, 95% CI [1.47, 1.84]). CONCLUSIONS/RELEVANCE: This analysis of real-world claims data shows lower rates of stroke, thromboembolism, and major bleeding, as well as fewer emergency department visits, with patient self-testing compared to office-based/lab INR monitoring. Our finding that PST is safe and effective among current users suggests that more patients may benefit from its use.

Decentralization and Virtualization of INR-based Anticoagulation Control During the COVID-19 Pandemic.

OBJECTIVE: To investigate the effectiveness of the decentralization and virtualization of anticoagulation clinics just before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a cohort study investigation at Prince Sultan Cardiac Clinics PSCC Qassim region, Saudi Arabia. To evaluate the effectiveness of the virtual coagulation clinic, we calculated the time in therapeutic range (TTR), Morisky score for adherence, and satisfaction. Demographics of the patients were analyzed to group patients based on their regions or districts to facilitate the visits. Thirteen different PHCs/Hospitals were allocated for decentralization based on patient density in that region. Intensive courses were provided for all general practitioners (GPs) regarding warfarin anticoagulation and point of care testing (POCT) using iSTAT. All appointments were scheduled by WhatsApp, with no more actual visits to the main center. RESULTS: Among the included participants (n = 5616), 61.1% were females, 38.9% were males, and the mean age was 60.5 (18-85) years. The total number of clinic visits was 7303 per month, with an average of 1.3 visits per patient. Approximately 95% of the participants had a valvular indication to receive anticoagulation; of them, 55% underwent mitral valve replacement. Moreover, after the virtualization of the INR clinic, keeping INR levels within a therapeutic range was reported in 80% of patients. Regarding patient satisfaction, 90% of the total population was satisfied by the new experience. CONCLUSION: Decentralization and virtualization of the INR clinic have similar TTR results if conducted properly.

Reliability of International Normalized Ratio Results in the CoaguChek Pro II System in a Clinical Setting.

The National Institute of Cardiology has previously used the CoaguChek® XS Plus system (Roche Diagnostics International Ltd), comparing capillary blood prothrombin time/international normalized ratio (PT/INR) results with those obtained using BCS-XP/Thromborel (Siemens). We assessed the reliability of PT/INR results using the third-generation CoaguChek Pro II system, the CoaguChek XS Plus system, and cobas® t 411 for citrated plasma analysis. Venous and capillary PT/INR were measured (N = 204). Spearman's correlation, Bland-Altman, and concordance analysis between methods were conducted. Spearman's correlation coefficients between venous/capillary INR were high for CoaguChek Pro II versus CoaguChek XS Plus (r = 0.994), CoaguChek Pro II versus cobas t 411 (r = 0.967), and CoaguChek XS Plus versus cobas t 411 (r = 0.968). Good concordance was observed among capillary methods (concordance coefficient [κ] = 0.888) and remaining relationships (P < .001 for all): cobas t 411 versus CoaguChek XS Plus (κ = 0.696) and cobas t 411 versus CoaguChek Pro II (κ = 0.684). In conclusion, good agreement was observed between CoaguChek Pro II, CoaguChek XS Plus, and cobas t 411.

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.

Quality of Anticoagulation With Phenprocoumon and Warfarin in Left Ventricular Assist Device Patients: A Multicenter Study.

VISUAL ABSTRACT: of key results. INR, international normalized ratio; TTR, time in therapeutic range; PTR, percentage of tests in range; HRAE, hemocompatibility-related adverse event; FFUV, first follow-up visit; GIB, gastrointestinal bleeding; HR, hazard ratio.http://links.lww.com/ASAIO/A961.

Estimating the measurement uncertainties of the international sensitivity index of 12 thromboplastins through Monte Carlo simulation.

BACKGROUND: Measurement uncertainty (MU) estimation has become an important process in clinical laboratories; however, calculating the MUs of the international sensitivity index (ISI) of thromboplastins is difficult because of the complex mathematical calculations required in calibration. Therefore, this study quantifies the MUs of ISIs through the Monte Carlo simulation (MCS), which involves random sampling of numerical values to solve a complex mathematical calculation. METHODS: Eighty blood plasmas and commercially available certified plasmas (ISI Calibrate) were used to assign the ISIs of each thromboplastin. Prothrombin times were measured using reference thromboplastin and 12 commercially available thromboplastins (Coagpia PT-N, PT Rec, ReadiPlasTin, RecombiPlasTin 2G, PT-Fibrinogen, PT-Fibrinogen HS PLUS, Prothrombin Time Assay, Thromboplastin D, Thromborel S, STA-Neoplastine CI Plus, STA-Neoplastine R 15, and STA-NeoPTimal) with two automated coagulation instruments: ACL TOP 750 CTS (ACL TOP; Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). Then, the MUs of each ISI were simulated through MCS. RESULTS: The MUs of ISIs ranged from 9.7 % to 12.1 % and 11.6 % to 12.0 % when blood plasma and ISI Calibrate were used, respectively. For some thromboplastins, the ISI claimed by manufacturers significantly differed from the estimated results. CONCLUSIONS: MCS is adequate to estimate the MUs of ISI. These results would be clinically useful for estimating the MUs of the international normalized ratio in clinical laboratories. However, the claimed ISI significantly differed from the estimated ISI of some thromboplastins. Therefore, manufacturers should provide more accurate information about the ISI value of thromboplastins.

Potential Drug Interaction Between Favipiravir and Warfarin in Patients With COVID-19: A Real-World Observational Study.

Favipiravir is one of the most used antiviral agents for the treatment of coronavirus disease 2019 infection in many countries, including Thailand. This study aimed to investigate the effect of favipiravir-warfarin interaction in terms of changes in international normalized ratio (INR) of patients. Medication charts of all inpatients in a hospital in Thailand between April 2021 and March 2022 were reviewed. Patients who received either warfarin with standard care or warfarin with favipiravir were included. The INR levels of patients were monitored at baseline and the earliest date following treatment, as well as other laboratory parameters. There were 43 and 53 patients in the warfarin-favipiravir and the warfarin-only groups, respectively. Baseline characteristics, such as sex, age, body mass index, and warfarin dose, were not significantly different between the 2 groups. The results showed that the mean INR of patients using favipiravir and warfarin was increased from 2.14 to 3.88 (P < .001), while the patients using warfarin alone had no increase in the mean INR (1.93 vs 1.91; P = .906). Other parameters were not significantly changed, including white blood cell count, red blood cell count, hemoglobin, hematocrit, and liver function. However, an increase in platelet count was observed in the favipiravir-warfarin group, but not in the control group. This real-world study highlighted a significant increase in the INR levels of patients who used favipiravir together with warfarin, compared to patients who used only warfarin. However, the interaction did not affect other laboratory parameters, except an increase in platelet count.

Data mining for prothrombin time and international normalized ratio reference intervals in children.

Reference intervals (RIs) help physicians in differentiating healthy from sick individuals. The prothrombin time (PT) and International normalized ratio (INR) fluctuate in coagulation pathway defects and have interlaboratory variability due to the instrument/reagent used. As direct method is difficult in children, we chose an indirect data mining method for the determining PT/INR RIs. The indirect method overcomes the substantial financial and logistic challenges, and ethical restrictions in children, moreover, allows partitioning in more fine-grained age groups. Prothrombin Time/INR measurements performed in patients aged birth-18 years between January 2013 and December 2020, were retrieved from laboratory management system of the Aga Khan Hospital. Reference intervals were computed using an indirect KOSMIC algorithm. The KOSMIC package function on the assumption that the non-pathologic samples follow a Gaussian distribution (after Box-Cox transformation of the data), following an elaborate statistical process to isolate distribution of physiological samples from mixed dataset. A total of 56,712 and 52,245 values were retrieved for PT and INR respectively. After the exclusion of patients with multiple specimens obtained during the study period, RIs were calculated for 37,356 (PT) and 37,192 (INR) children with stratification into 9 age groups. A comparison of 2.5th and 97.5th percentile results with those of established RIs from SickKids Handbook of Pediatric Thrombosis and Hemostasis demonstrated good agreement in between different age groups. This study supports data mining as an alternate approach for establishing PT/INR RIs, specifically in resource-limited settings. The results obtained are specific to studied population and instrument/reagent used. The study also allows understanding of fluctuations in coagulation pathways with increasing age and hence better clinical decision-making based on PT and INR results.

Impact of pharmacist intervention on anticoagulation management and risk for potential COVID-19 exposure during the COVID-19 pandemic.

INTRODUCTION: Patients taking warfarin require frequent international normalized ratio (INR) monitoring in healthcare settings, putting them at increased risk of Coronavirus disease 2019 (COVID-19) exposure during the pandemic. Thus, strategies to limit in-person visits to healthcare facilities were recommended by the Anticoagulation Forum. The objective of this study was to describe the number and types of changes made to anticoagulation therapy as a result of pharmacist intervention during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective chart review of patients included in a primary care COVID-19 anticoagulation intervention was conducted. During this intervention, pharmacists provided individualized recommendations for anticoagulation changes in patients taking warfarin to limit their healthcare facility exposure while also maintaining safe anticoagulation management practices. RESULTS: As a result of pharmacist intervention, 83 (55.7 %) of the 149 patients included in the intervention had changes in anticoagulation including: switching to a direct oral anticoagulant (n = 12), extending the INR monitoring interval (n = 48), switching to home INR monitoring (n = 21), or stopping anticoagulation (n = 2). For those patients who were taking warfarin for the entire 6 months pre- and post-intervention, the total number of healthcare facility and laboratory visits with an INR completed decreased from 8.8 to 6.4 (p < 0.001) per patient without a statistically significant decrease in time in therapeutic range (p = 0.76). CONCLUSIONS: This study depicts rapid implementation of a population health-based approach to assess all patients taking warfarin for options to minimize healthcare visits and decrease risk for COVID-19 exposure. Methods to reduce healthcare visit burden while maintaining patient safety should be considered as a regular component of anticoagulation management post-pandemic.

Quality of Oral Anticoagulation in Atrial Fibrillation Patients at a Tertiary Hospital in Brazil. / Qualidade da Anticoagulação Oral em Pacientes com Fibrilação Atrial em um Hospital Terciário no Brasil.

BACKGROUND: Atrial fibrillation (AF) affects 0.5% to 2.0% of the general population and is usually associated with cardiac structural diseases, hemodynamic damage, and thromboembolic complications. Oral anticoagulation prevents thromboembolic events and is monitored by the international normalized ratio (INR). OBJECTIVES: To evaluate INR stability in nonvalvular AF patients treated with warfarin anticoagulation, to evaluate thromboembolic or hemorrhagic complications, and to identify the group at higher risk for thromboembolic or hemorrhagic events. METHODS: Data from the medical records of 203 patients who received medical care at a tertiary hospital in Brazil were reviewed, and the time in therapeutic range (TTR) was calculated using the Rosendaal method. The possible TTR influencing factors were then analyzed, and the relationship between the TTR and thromboembolic or hemorrhagic events was calculated. The level of significance was 5%. RESULTS: The mean TTR was 52.2%. Patients with INR instability in the adaptation phase had a lower mean TTR (46.8%) than those without instability (53.9%). Among the studied patients, 6.9% suffered hemorrhagic events, and 8.4% had a stroke. The higher risk group for stroke and bleeding consisted of patients with INR instability in the adaptation phase. CONCLUSIONS: The quality of anticoagulation in this tertiary hospital in Brazil is similar to that in centers in developing countries. Patients with greater INR instability in the adaptation phase evolved to a lower mean TTR during follow-up, had a 4.94-fold greater chance of stroke, and had a 3.35-fold greater chance of bleeding. Thus, for this patient group, individualizing the choice of anticoagulation therapy would be advised, considering the cost-benefit ratio.

FUNDAMENTO: A fibrilação atrial (FA) afeta de 0,5% a 2,0% da população geral e geralmente está associada a doenças estruturais cardíacas, comprometimento hemodinâmico e complicações tromboembólicas. A anticoagulação oral previne eventos tromboembólicos e é monitorada pela razão normalizada internacional (RNI). OBJETIVOS: Avaliar a estabilidade do RNI em pacientes com FA não valvar tratados com anticoagulante varfarina, avaliar complicações tromboembólicas ou hemorrágicas e identificar o grupo com risco mais alto de eventos tromboembólicos ou hemorrágicos. MÉTODOS: Dados de prontuários médicos de 203 pacientes atendidos em um hospital terciário no Brasil foram analisados e o tempo de intervalo terapêutico (TTR) foi calculado usando-se o método Rosendaal. Em seguida possíveis fatores que influenciam o TTR foram analisados e a relação entre TTR e eventos tromboembólicos ou hemorrágicos foi calculada. O nível de significância foi 5%. RESULTADOS: O TTR médio foi 52,2%. Pacientes com instabilidade de RNI na fase de adaptação tinham um TTR médio mais baixo (46,8%) do que aqueles sem instabilidade (53,9%). Entre os pacientes estudados, 6,9% sofreram eventos hemorrágicos e 8,4% tiveram um acidente vascular cerebral. O grupo com risco mais alto de acidente vascular cerebral e sangramento era composto de pacientes com instabilidade de RNI na fase de adaptação. CONCLUSÕES: A qualidade da anticoagulação nesse hospital terciário no Brasil é semelhante à de centros de países em desenvolvimento. Pacientes com instabilidade de RNI maior na fase de adaptação evoluíram para um TTR médio mais baixo durante o acompanhamento, tinham uma chance de acidente vascular cerebral 4,94 vezes maior e uma chance de sangramento 3,35 vezes maior. Portanto, para esse grupo de pacientes, individualizar a escolha de tratamento anticoagulante seria recomendado, considerando-se a relação custo-benefício.

Online KidClot education for patients and families initiating warfarin therapy: The eKITE study.

Anticoagulation with Vitamin K antagonists (VKA) has always posed challenges in terms of monitoring requirements. These challenges were further exacerbated in the setting of the COVID-19 pandemic, with limited access to and/or avoidance of laboratory testing. The importance of utilizing point of care (POC) health technology for individualized patient management is salient. The foundation of effective home INR monitoring is establishing patient knowledge about their therapy and INR testing proficiency. The eKITE series was developed to support patients in establishing foundational knowledge required for VKA (warfarin) management and INR monitoring. The primary objectives were to evaluate eKITE, a patient-oriented innovative online education program for warfarin therapy, participant learning stress, and patient preference for online learning. This multi-center prospective study provided patients access to warfarin online education. Participants were required to complete written quizzes assessing warfarin knowledge of key concepts proficiency and identifying knowledge deficits. Patient preference, evaluating calm (lack of anxiety) while learning, and an INR on a home meter was completed. Participants performed INR tests at home and reported INRs by telephone. The analysis included 144 children and caregivers enrolled at five US and CDN sites. Most indications for anticoagulation were cardiac (congenital or acquired heart disease) with varied INR target ranges. Mean knowledge scores for warfarin and INR self-testing modules were 97%, with low anxiety with TTR of 84%. Patient preferred online learning. eKITE is an effective teaching modality for warfarin/home INR monitoring with safe INR testing and warfarin management that is appropriate for pediatrics and adults alike. PROLOGUE: The whir in the hallways is deafening. Lights bright, alarms are ringing in a chorus of unsynchronized beeps and screeches. It has been more than a week since I have slept. Snuggled beside me is my precious child, whining and equally irritated with the asynchronous symphony, further compounded by anxiety, procedures, and pain. The sun has broken. The staff smiles are welcoming and incessant, as one after one, they approach hurried, urgent, assiduous, their need to coach me for our upcoming departure to the warmth of home. Each provides essential information that I will require to keep my child, my treasure, safe and healthy. Yet, my eyes are heavy, blurred, and my brain foggy, trapped in a dark heavy cloud. How am I to follow? Comprehend? and retain anything? As they instruct, my precious child yearns for loving arms, compassion and love, whining, crying in disquiet. Overwhelmed does not adequately describe my ineffable exhaustion. Amidst this, how am I to learn about warfarin? Such a challenging medication, with so much to know. Concentrate, I tell myself, focus; now is my only opportunity to learn. I must be alert. It seems to be nonsensical.

CoaguChek® XS versus standard laboratory prothrombin time for anticoagulant monitoring in patients with antiphospholipid syndrome.

INTRODUCTION: The standard of care for thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). Prothrombin time, and its corresponding international normalized ratio (INR), is the laboratory test routinely performed to assess anticoagulation. Self-management of VKA therapy using point-of-care (POC) devices seems to be an attractive option. PURPOSE/OBJECTIVE: To evaluate the accuracy of a POC device (CoaguChek XS) in APS patients by comparing it with venous laboratory INR. Furthermore, we analyzed whether other clinical and laboratory features could interfere with the CoaguChek XS results. PATIENTS AND METHODS: This is a single-center cross-sectional study with 94 APS patients from a tertiary rheumatology clinic performed from August 2014 to March 2015. The comparison between CoaguChek XS and venous laboratory INR results was evaluated using the coefficient of determination (r) followed by the Bland-Altman test. A paired t-test was also applied. A difference of up to ±0.5 INR unit between the two systems was considered clinically acceptable. RESULTS: The mean CoaguChek-INR was 2.94 ± 1.41 and venous laboratory INR was 2.43±0.86, with a correlation coefficient (r) of 0.95. Categorizing INR values in ranges (INR <2, INR 2-3, INR 3-4, and INR >4), we found that the INR >4 group presented a lower correlation (r = 0.64) compared to the other ranges (p < 0.05). Although both methods were highly correlated, CoaguChek XS showed higher values than the venous laboratory INR, with an increased average of 0.42 ± 0.54. Therefore, we proposed a simple linear regression model to predict the venous laboratory INR values, using results obtained from CoaguChek XS. A difference ≤0.5 INR unit between the two systems was observed in 57.4% of patients, and the aPL profile did not influence the results. CONCLUSION: Although CoaguChek XS and venous laboratory INR demonstrated a good linear correlation in the group of INR ≤4, extra caution should be taken in APS patients, since a reasonable proportion of patients can present differences in INR results that are not acceptable. We do not recommend routine POC in APS patients.

Warfarin monitoring and interference by lupus anticoagulant in patients with antiphospholipid syndrome.

INTRODUCTION: Patients with antiphospholipid syndrome (APS) receive vitamin K antagonists, which warrants international normalized ratio (INR) monitoring. Research has indicated that presence of lupus anticoagulant (LA) can interfere with INR results obtained by point-of-care testing (POCT) devices. We aimed to investigate whether a systematic difference exists between POCT-INR and plasma-INR in patients with APS. MATERIALS AND METHODS: We compared 291 paired POCT- and plasma-INR results from 52 LA-positive APS patients receiving warfarin with each patient having a minimum of three paired measurements of paired POCT-INR (CoaguChek, Roche Diagnostics) and plasma-INR. Agreement limits were considered satisfactory if differences were within ±0.4 INR for plasma-INR < 2.0, within ±20% for plasma-INR 2.0 to 3.5, within ±20% for plasma-INR > 3.5 to 4.5, within ±25% for plasma-INR > 4.5 to 6.0 and within ±30% for plasma-INR > 6.0. RESULTS: A strong positive correlation was found between POCT- and plasma-INR, Spearman's rho (95% CI) = 0.72 (0.65-0.78), p < 0.001. The average bias was 0.1 INR (3.7%), p < 0.001. 79% of paired INR results met the agreement limits with 67% of the diverging POCT-INRs being from a subset of five patients, who had consistently higher POCT- than plasma-INR. CONCLUSIONS: The majority of LA-positive APS patients had no clinically significant difference between POCT-INR and plasma-INR. However, in a subset of patients, clinically significant systematic differences were found. Consequently, systematic comparison of a minimum three paired POCT- and plasma-INR results is recommended before implementing POCT-INR monitoring in LA-positive APS patients.

Polymethyl Methacrylate-Based Smart Microfluidic Point-of-Care Testing of Prothrombin Time and International Normalized Ratio through Optical Detection.

The mechanical heart valve is a crucial solution for many patients. However, it cannot function on the state of blood as human tissue valves. Thus, people with mechanical valves are put under anticoagulant therapy. A good measurement of the state of blood and how long it takes blood to form clots is the prothrombin time (PT); moreover, it is an indicator of how well the anticoagulant therapy is, and of whether the response of the patient to the drug is as needed. For a more specific standardized measurement of coagulation time, an international normalized ratio (INR) is established. Clinical testing of INR and PT is relatively easy. However, it requires the patient to visit the clinic for evaluation purposes. Many techniques are therefore being developed to provide PT and INR self-testing devices. Unfortunately, those solutions are either inaccurate, complex, or expensive. The present work approaches the design of an anticoagulation self-monitoring device that is easy to use, accurate, and relatively inexpensive. Hence, a two-channel polymethyl methacrylate-based microfluidic point-of-care (POC) smart device has been developed. The Arduino based lab-on-a-chip device applies optical properties to a small amount of blood. The achieved accuracy is 96.7%.

Micro-mechanical blood clot testing using smartphones.

Frequent prothrombin time (PT) and international normalized ratio (INR) testing is critical for millions of people on lifelong anticoagulation with warfarin. Currently, testing is performed in hospital laboratories or with expensive point-of-care devices limiting the ability to test frequently and affordably. We report a proof-of-concept PT/INR testing system that uses the vibration motor and camera on smartphones to track micro-mechanical movements of a copper particle. The smartphone system computed the PT/INR with inter-class correlation coefficients of 0.963 and 0.966, compared to a clinical-grade coagulation analyzer for 140 plasma samples and demonstrated similar results for 80 whole blood samples using a single drop of blood (10 µl). When tested with 79 blood samples with coagulopathic conditions, the smartphone system demonstrated a correlation of 0.974 for both PT/INR. Given the ubiquity of smartphones in the global setting, this proof-of-concept technology may provide affordable and effective PT and INR testing in low-resource environments.

Efficacy and safety of app-based remote warfarin management during COVID-19-related lockdown: a retrospective cohort study.

This study aimed to explore the effectiveness, and safety of internet-based warfarin management during the pandemic. In this single-center retrospective cohort study, we compared the safety and efficacy of online warfarin management using a smartphone app (the Alfalfa app) versus conventional outpatient clinic management from January 1, 2020 to March 31, 2020. Patients in the online management group used the Alfalfa app to communicate coagulation test results and other relevant information to a doctor or clinical pharmacist, who then responded with the dose adjustment plan and the date of the next blood test. The outcomes examined were the time in therapeutic range (TTR), incidence of clinical events (i.e., bleeding events, thrombotic events, warfarin-related emergency department visits, and warfarin-related hospital admissions), and the distribution of international normalized ratio (INR) values. Data from 117 patients were analyzed in this study. TTR was significantly higher in the online group than in the offline group (61.0% vs. 39.6%, P < 0.01). Incidence of major bleeding events, thrombotic events, and warfarin-related hospital admissions were comparable between the online and offline groups. However, minor bleeds (5.3% vs. 28.3%, P < 0.01) and warfarin-related emergency department visits (1.8% vs. 23.3%, P = 0.02) were significantly fewer in the online group than in the offline group. The proportion of INR values in the therapeutic range (53.8% vs. 40.1%, P < 0.01) was significantly higher in the online group. Warfarin management using the Alfalfa app appears to be a safe and effective method for warfarin management when patients cannot physically visit hospitals for follow-up.

Variables affecting the quality of anticoagulation in atrial fibrillation patients newly initiating vitamin K antagonists: insights from the national and multicentre SULTAN registry.

AIMS: Vitamin K antagonists (VKAs) are effective drugs reducing the risk for stroke in atrial fibrillation (AF), but the benefits derived from such therapy depend on the international normalized ratio (INR) maintenance in a narrow therapeutic range. Here, we aimed to determine independent variables driving poor anticoagulation control [defined as a time in therapeutic range (TTR) <65%] in a 'real world' national cohort of AF patients. METHODS AND RESULTS: The SULTAN registry is a multicentre, prospective study, involving patients with non-valvular AF from 72 cardiology units expert in AF in Spain. At inclusion, all patients naïve for oral anticoagulation were started with VKAs for the first time. For the analysis, the first month of anticoagulation and those patients with <3 INR determinations were disregarded. Patients were followed up during 1 year. A total of 870 patients (53.9% male, the mean age of 73.6 ± 9.2 years, mean CHA2DS2-VASc and HAS-BLED of 3.3 ± 1.5 and 1.4 ± 0.9, respectively) were included in the full analysis set. In overall, 7889 INR determinations were available. At 1-year, the mean TTR was 63.1 ± 22.1% and 49.2% patients had a TTR < 65%. Multivariate Cox regression analysis showed that coronary artery disease [odds ratio (OR) 1.81, 95% confidence interval (CI) 1.14-2.87; P = 0.012] and amiodarone use (OR 1.54, 95% CI 1.01-2.34; P = 0.046) were independently associated with poor quality of anticoagulation (TTR <65%). CONCLUSION: This study demonstrated that the quality of anticoagulation in AF patients newly starting VKAs is sub-optimal. Previous coronary artery disease and concomitant use of amiodarone were identified as independent variables affecting the poor quality of VKA therapy during the first year.

Improved Time in Therapeutic Range with International Normalized Ratio Remote Monitoring for Patients with Left Ventricular Assist Devices.

Despite advances in therapy, bleeding and thromboembolic events are frequent complications in patients with left ventricular assist device (LVAD) support. Maintaining warfarin in therapeutic range has been shown to be more challenging in this patient population compared to other indications. Patients with LVADs on warfarin typically are within goal international normalized ratio (INR) range 36-57% of the time, compared to about 65% for other indications. The goal of this study was to evaluate if an INR remote monitoring system along with the implementation of a standardized warfarin management protocol improves warfarin time in therapeutic range (TTR) for patients with LVADs. This single-center, retrospective, observational study included 78 patients with LVADs that were followed at our academic center from January 2015 to October 2017. In October 2016, we updated our warfarin management protocol and implemented a remote monitoring system with patients' weekly INR results monitored. The primary objective of the study was to determine the difference between TTRs in remote monitoring versus standard monitoring. We found that the average TTR was significantly higher in the remote monitoring group compared to the standard monitoring cohort (61.1% vs. 40.0%, p < 0.005). However, bleeding, thrombotic incidence, and hospital readmission rates were similar between the two patient cohorts. Remote monitoring improved warfarin TTR significantly in this study and may have the potential to improve anticoagulation-related outcomes in patients with LVADs.

Using a Simple Prescription Gap to Determine Warfarin Discontinuation Can Lead to Substantial Misclassification.

BACKGROUND: Warfarin remains widely used and a key comparator in studies of other direct oral anticoagulants. As longer-than-needed warfarin prescriptions are often provided to allow for dosing adjustments according to international normalized ratios (INRs), the common practice of using a short allowable gap between dispensings to define warfarin discontinuation may lead to substantial misclassification of warfarin exposure. We aimed to quantify such misclassification and determine the optimal algorithm to define warfarin discontinuation. METHODS: We linked Medicare claims data from 2007 to 2014 with a multicenter electronic health records system. The study cohort comprised patients ≥65 years with atrial fibrillation and venous thromboembolism initiating warfarin. We compared results when defining warfarin discontinuation by (1) different gaps (3, 7, 14, 30, and 60 days) between dispensings and (2) having a gap ≤60 days or bridging larger gaps if there was INR ordering at least every 42 days (60_INR). Discontinuation was considered misclassified if there was an INR ≥2 within 7 days after the discontinuation date. RESULTS: Among 3,229 patients, a shorter gap resulted in a shorter mean follow-up time (82, 95, 117, 159, 196, and 259 days for gaps of 3, 7, 14, 30, 60, and 60_INR, respectively; p < 0.001). Incorporating INR (60_INR) can reduce misclassification of warfarin discontinuation from 68 to 4% (p < 0.001). The on-treatment risk estimation of clinical endpoints varied significantly by discontinuation definitions. CONCLUSION: Using a short gap between warfarin dispensings to define discontinuation may lead to substantial misclassification, which can be improved by incorporating intervening INR codes.