International Normalized Ratio Results Research Articles

Anticoagulation control challenges in patients with rheumatic heart disease and mechanical heart valves operated at a cardiac surgery center in a low-income country

Abstract Background Rheumatic heart disease (RHD) prevalence is very high in many low-income countries and valve replacement surgery can sometimes be the only available therapeutic strategy for the affected patients. Mechanical valves require lifelong anticoagulation and this can be very challenging in many poor countries where several barriers to effective anticoagulation monitoring and management are faced. Methods This is a retrospective study on 145 patients with RHD who underwent valve replacement surgery at a cardiac surgery center (CSC) in a low-income country between 2001 and 2022. The study aimed to evaluate the effectiveness of anticoagulation treatment to prevent thromboembolic events in patients with RHD with mechanical valves. The patients’ information such as social and demographic data, clinical features, surgical data and international normalized ratio (INR) records were collected and analyzed. Descriptive statistics were applied to the data and expressed as mean with standard deviation or simple frequencies and percentages. Results The mean age of the operated patients was 25.9 years (± 12.6) and 60% of them were female. Most of the patients (54%) were able to monitor their anticoagulation at the center and 8.2% of them monitored it in other hospitals. Three percent (3%) of the patients use a portable device to monitor their INR. These devices are provided by the CSC to help patients that live in distant provinces and are unable to go to the capital regularly. The device is held by one patient that is a focal point and helps monitor the INR of the other patients living in the same province. The INR results are communicated to the CSC by telephone text message. Seven percent (7%) of the operated patients haven’t monitored their INR for more than one year and 24.8% of them were lost to follow-up. Sixty-four percent (64%) of the patients who monitor their INR at the center have an optimal control of their anticoagulation therapy. Most of the patients that were lost to follow-up (N=20) and most of the patients that haven’t checked their INR for more than one year (N=7) are patients who had aortic valve replacements. At least 20% of the patients that live in capital of the country and close to the CSC don’t monitor their anticoagulation regularly. Conclusion The surgical outcomes in RHD patients who undergo mitral valve repair are usually satisfactory. However, valve replacement is often the only feasible alternative and anticoagulation monitoring and management in these patients can become a serious problem especially to those coming from areas with limited resources. Illiteracy and poverty play a major role as barriers to effective monitoring of anticoagulation therapy. Efforts must be made to increase access to facilities where INR can be monitored. Our experience showed us that providing portable devices for INR monitoring to the patients living in remote areas can be a favorable short-term solution.

Frozen/Thawed Samples Can Replace Fresh Samples for Assignment of ISI to Secondary Thromboplastin Standards for Multiple Reagent/Instrument Combinations: Data to Support Possible Revision of WHO Guidelines.

Calibration of thromboplastins is required for accurate calculation of the international normalised ratio (INR). Accurate INR results are required for optimal dosing of vitamin K antagonists. Decreases in vitamin K antagonist usage have made the recruitment of sample sets for international sensitivity index (ISI) calibrations more difficult. A possible solution to this would be to allow the use of frozen-thawed samples in place of fresh plasmas in the calibration of secondary standards. We investigated the effect of freezing and thawing samples before usage in ISI calibrations of secondary standards. Multiple reagent/instruments were tested to identify the degree of difference between a fresh sample ISI calibration and one performed on frozen-thawed samples. Where possible, the two ISI calibrations were performed on the same sample set. Alternatively, a separate set of samples from different patients was used. The difference in ISI values was <3% for those datasets where the same samples were used, and <6% for those datasets where two sample sets were used. Additionally, other parameters required for a valid ISI calibration showed only minor differences-some calibrations showed fewer outliers in the frozen-thawed datasets. Mean normal prothrombin time for the international reference thromboplastins was <3.5% different across four different calibrations (two for rabbit thromboplastin and two for recombinant human thromboplastin). This modification to the WHO guidelines would facilitate the recruitment of test plasmas in advance of calibration solving the problem of requiring availability of fresh patient samples with a range of INRs in a 5-h window. Not a part of any clinical trial.

Observing INR Results in Patients Who Switched from Brand-Name to Generic Warfarin during the COVID-19 Pandemic at KAMC, Riyadh, Saudi Arabia

Abstract Background: Since the global spread of coronavirus disease 2019 (COVID-19), multiple challenges have faced the medical field, including the suspension of numerous drug companies, leading to a shortage in drug supplies to hospitals. Hospitals were required to use a bioequivalent generic form of a drug for continuing treatment of the patients. Objective: This study assessed the International Normalized Ratio (INR) score for the patients who were switched from Coumadin® (Bristol-Myers Squibb Pharma Company), brand-name warfarin, to a generic form of warfarin in the anticoagulant clinic due to the shortage of Coumadin® during the COVID-19 pandemic. Materials and Methods: A retrospective, cross-sectional chart review study was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. Patients who switched from Coumadin® to generic warfarin from February 2020 to February 2021 were included. This study compared the brand-name and generic forms of warfarin to determine their effectiveness and if the generic form can be used as a therapeutic equivalent. All the data were collected from the electronic health records in KAMC. Each patient file was reviewed for the INR results before and after the switch of warfarin to determine if there was a mean difference between the two variables. Results: In total, 2,197 patients’ medical records were reviewed, yielding 15,499 INR values. The majority (n = 1,362, 80.4%) of the 1,709 mechanical valve INRs were low (INR &lt; 2.1), and 10,697 (77.5%) of the non-mechanical valve INR values were low (INR &lt; 1.6). The Wilcoxon two-sample test was used to evaluate the change in the INR value before and after the switch. The results demonstrate that there is a statistical significance between the effectiveness of Coumadin and generic warfarin. The P values were 0.026 and &lt;0.0001 for the mechanical valve group and the non-mechanical valve group, respectively. Conclusion: The findings of this study indicate that there is a significant difference between the effectiveness of Coumadin and generic warfarin.

A qualitative study exploring patient experiences and opinions of warfarin patient self‐management in the US healthcare system

AbstractBackgroundDespite consensus guideline recommendations, the use of warfarin patient self‐management (PSM) in the United States (US) healthcare system remains underutilized.ObjectivesTo gain an understanding of the barriers and facilitators to warfarin PSM in US healthcare systems through qualitative exploration of the opinions of select US patients receiving warfarin therapy.MethodsIndividual patient interviews were conducted at five geographically diverse sites. Grounded theory analysis was performed on interview transcriptions using the consolidated framework for implementation research (CFIR) to identify facilitators and barriers to PSM implementation within the US healthcare system.ResultsA total of 40 patients were interviewed. Four major themes emerged from the interviews: (1) “Patients are resourceful problem solvers who know themselves better than clinicians” (CFIR domain “Characteristics of Individuals”); (2) The provider‐patient relationship is key to successful PSM (CFIR domains “Inner Setting” and “Intervention Characteristics”); (3) Patients are willing and interested in trying PSM if not already doing so (CFIR domains “Process,” “Intervention Characteristics,” “Inner Setting, and “Characteristics of Individuals”); and (4) Point‐of‐care international normalized ratio (INR) monitoring is an important PSM facilitator (CFIR “Intervention Characteristics,” “Outer Setting,” “Inner Setting,” and “Process” domains).ConclusionsInterview participants were willing and interested in trying PSM. Core elements of warfarin PSM include timely access to INR results, and a framework to support PSM decision making. Home INR monitoring is likely ideal for facilitating PSM implementation as is maintaining strong provider‐patient relationships where providers, including clinical pharmacists, trust their patients and act as a safety net for PSM decision making.

The Concordance between Laboratory and POCT INR and the Value of Bedside Measurement of INR in Patients on Warfarin Undergoing Dental Procedures: A Prospective Cohort Study

Introduction: Patients on anticoagulation particularly warfarin suffers when they have a dental problem that requires intervention. Most of dentists worry and refuse to perform procedures on patients on warfarin because of the risk of bleeding and request the availability of international normalized ratio (INR) results before procedure which can delay the procedure and add another burden on the patient particularly who live away from the treating center. Objective: To evaluate the efficacy and the value of using point of care testing (POCT) (INR) in patients on warfarin undergoing dental procedures. We also had analyzed the frequency and severity of dental bleeding in patients on warfarin therapy and the concordance between Laboratory based INR and POCT INR. This is the first interim analysis on ongoing prospective study. Methods: A cohort study of 30 patients on chronic use of anticoagulation therapy with warfarin for different clinical indications who planned to undergo dental procedures at a teaching hospital in Saudi Arabia. The patients' demographic and clinical characteristics, type and severity of bleeding, and INR measured by both HemoChrone (POCT) and prothrombin time (PT) were performed at same time. Descriptive statistics, paired samples statistics, correlations, and analysis of variance (ANOVA) were performed. Results: The sample consisted of 60% females, with a mean age of 49.9 (SD 13.3) years. The most common indications for warfarin therapy were mechanical aortic valve replacement (56.7%), atrial fibrillation (13.3%), and atrial flutter (16.7%). Before the procedure, the mean Laboratory INR was 2.6 (SD 0.6) and the mean HemoChrone POCT INR was 2.8 (SD 0.8). There was a significant positive correlation between the two methods (r = 0.81, p &amp;lt; 0.001). There was no significant difference in the INR and type of bleeding, dentist performed the procedure, or dose of warfarin. There was no correlation between the Bleeding severity or type and the INR level in patients undergoing different dental procedures. Even among those with HemoChrone POCT INR &amp;gt; 3, which is considered high and increases the risk of bleeding, there was no significant correlation with bleeding. Conclusion: These results imply that warfarin therapy can be safely continued for most dental procedures without increasing the risk of bleeding regardless of the INR results. The HemoChrone POCT INR is a dependable and practical method to monitor the effect of warfarin in dental settings which can reassure the dentists before procedure. Figure 1: The concordance between Laboratory and POCT INR

Position Statement on In-hospital/Clinic Point-of-care Coagulation Testing for Anticoagulation Monitoring in Saudi Arabia.

Hospital overload is a persistent occurrence in daily practice. Interventions such as point-of-care testing (POCT) are needed to alleviate the pressure faced by healthcare providers and administrators. An invited panel of experts from Saudi Arabia was formed under the auspices of the Saudi Heart Association in order to discuss local treatment gaps in the management of patients receiving anticoagulation therapy. This was done in a series of meetings, which resulted in the development of official recommendations for the implementation of POCT for anticoagulation monitoring in the country. Recommendations were based on a comprehensive literature review and international guidelines taking into consideration local clinical practice, clinical gaps, and treatment/testing availabilities. Vitamin K antagonist (VKA)-based anticoagulation therapy requires routine monitoring. POCT is a promising model of care for the monitoring of International Normalized Ratio (INR) in patients receiving oral anticoagulation in terms efficacy, safety and convenience. The availability of POC INR testing should not replace the use of standard laboratory anticoagulation monitoring. However, there are several indications for implementing POCTINR monitoring that was agreed upon by the expert panel. POCT for anticoagulation monitoring should primarily be used in the warfarin (or other VKA) monitoring clinic in order to ensure treatment efficiency, cost-effectiveness of care, patient satisfaction, and quality of life improvement. The expert panel detailed the requirements for the establishment of a warfarin (or other VKA) monitoring clinic in terms of organization, safety, quality control, and other logistic and technical considerations. The limitations of POCT should be recognized and recommendations on best practices should be strictly followed. Core laboratory confirmation should be sought for patients with higher INR results (>4.7) on POCT. Proper training, quality control, and regulatory oversight are also critical for preserving the accuracy and reliability of POCT results. POCT enables more rapid clinical decision-making in the process of diagnosis (rule-in or rule-out), treatment choice and monitoring, and prognosis, as well as operational decision-making and resource utilization. POCT thus can fulfill an important role in clinical practice, particularly for patients receiving VKAs.

The international normalised ratio to monitor coagulation factor production during normothermic machine perfusion of human donor livers

BackgroundNormothermic machine perfusion (NMP) of donor livers allows for new diagnostic and therapeutic strategies. As the liver produces most of the haemostatic proteins, coagulation assays such as the International Normalised Ratio (INR) performed in perfusate may be useful to assess hepatocellular function of donor livers undergoing NMP. However, high concentrations of heparin and low levels of fibrinogen may affect coagulation assays. MethodsThirty donor livers that underwent NMP were retrospectively included in this study, of which 18 were subsequently transplanted. We measured INRs in perfusate in presence or absence of exogenously added fibrinogen and/or polybrene. Additionally, we prospectively included 14 donor livers that underwent NMP (of which 11 were transplanted) and measured INR using both a laboratory coagulation analyser and a point-of-care device. ResultsIn untreated perfusate samples, the INR was above the detection limit in all donor livers. Addition of both fibrinogen and polybrene was required for adequate INR assessment. INRs decreased over time and detectable perfusate INR values were found in 17/18 donor livers at the end of NMP. INR results were similar between the coagulation analyser and the point-of-care device, but did not correlate with established hepatocellular viability criteria. ConclusionsMost of the donor livers that were transplanted showed a detectable perfusate INR at the end of NMP, but samples require processing to allow for INR measurements using laboratory coagulation analysers. Point-of-care devices bypass this need for processing. The INR does not correlate with established viability criteria and might therefore have additional predictive value.

Evaluating the Effect of Timing on Point-of-Care Testing of INR

Objectives: To evaluate if there is a difference in International Normalized Ratio (INR) readings taken within the 15 second time frame after lancing the finger vs 30-60 seconds of obtaining a blood drop utilizing a CoaguChek® XS Plus point-of-care (POC) INR machine in patients on warfarin therapy. Methods: All adult patients on anticoagulation therapy with warfarin who were managed in a pharmacist-run anticoagulation clinic were considered for inclusion in the study. The mean difference of INR readings taken less than 15 seconds vs between 30-60 seconds after the blood drop was obtained from the finger was assessed. Results: A total of 62 pairs of INR results were included in the study. There was a mean difference in INR of .076 (95% CI 0.011-.140; P = .0217) when comparing INR readings taken less than 15 seconds and between 30-60 seconds after the blood drop was obtained from the finger. Conclusions: There was a significant difference in INR readings taken less than 15 seconds vs 30-60 seconds after obtaining the blood drop when utilizing a POC INR machine. INR readings taken 30-60 seconds after obtaining a blood drop with the CoaguChek® XS Plus POC INR machine is not acceptable for use to monitor patients on warfarin.

Effect of troponin I and coagulation parameters on mortality in COVID-19 patients

Objective: Our aim is to determine the levels of troponin-I and some coagulation markers (D-dimer, fibrinogen and International Normalized Ratio (INR)) in coronavirus disease 2019 (COVID-19) patients and to investigate the effects of these markers on mortality.&#x0D; Patients and Methods: It is planned as a descriptive, cross-sectional and analytical study. The study was conducted by retrospectively scanning the files of COVID-19 patients who applied to Inonu University Turgut Ozal Medical Center between 01.03.2020 and 31.12.2020. Levels of cardiac troponin I markers and coagulation parameters (D-dimer, fibrinogen and INR) were detected.&#x0D; Results: The results of a total of 1858 patients were obtained. One thousand, three hundred and twenty-six patients with only troponin I and D-dimer results (Group 1), 606 patients with only troponin I and fibrinogen results (Group 2), and 1308 patients with only troponin I and INR results (Group 3) were included. Troponin I levels were significantly higher in all patients who died. 96.6% of the patients with high D-dimer levels died in Group 1, 85.5% of the patients with high fibrinogen levels died in Group 2 and 77.3 % of the patients with high INR levels died in Group 3. &#x0D; Conclusion: Measurements of troponin-I and coagulation markers such as D-dimer, fibrinogen and INR can help predict clinical severity and mortality in COVID-19 patients.

Quality of anticoagulation with the use of warfarin in long-term care in a tertiary care hospital using time spent in therapeutic range as a predictive parameter

ABSTRACT Background: Warfarin was a frequently prescribed long-term anticoagulant before the advent of novel oral anticoagulants or direct oral anticoagulants. These drugs are used for the primary or secondary prevention of stroke in patients with atrial fibrillation or for the treatment and prophylactic prevention of venous thromboembolism. This study aimed to assess the anticoagulation control of patients receiving warfarin at a tertiary care hospital. Methods: This retrospective cohort study was conducted in an anticoagulation clinic at a tertiary care hospital in Saudi Arabia and included 113 patients who had been treated with warfarin for at least 3 months. Thereafter, the international normalized ratio results were collected for 3 years. Anticoagulation control was assessed by calculating time within the therapeutic range (TTR) as per the Rosendaal method. Results: A total of 113 patients (mean age, 56 ± 17.6 years; 64.6% of females) were included. The mean TTR was 48.1%. Almost one-third of the patients (31.3%) had poor anticoagulation control defined as a TTR of &lt;50%. Poor anticoagulation control was significantly associated with a higher CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke/transient ischemic attack) score (P = 0.043). TTR did not differ significantly between men and women, and it was not associated with age or anticoagulation therapy duration. Conclusion: Anticoagulation quality was suboptimal in patients receiving warfarin in a tertiary care hospital, with nearly 41% of time spent outside the therapeutic range. Methods should be implemented to improve anticoagulation control in appropriate patient groups.

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.

Using three external quality assurance schemes to achieve equivalent international normalized ratio results in primary and secondary healthcare

Accurate prothrombin time international normalized ratio (INR) results are essential for safe anticoagulation treatment. Patients are treated both in primary and secondary healthcare, therefore equivalence of INR results from point-of-care (POC) and hospital measurement procedures (MPs) are important. It is not possible to evaluate this equivalence in traditional external quality assessment (EQA). The aim of this paper is to describe a special quality assurance system consisting of three different EQA schemes to monitor the harmonization of INR results in Norway. The EQA scheme for hospital laboratories uses commutable control materials and evaluates participant performance and the equivalence of hospital MPs. The EQA scheme for primary healthcare laboratories uses non-commutable control materials and evaluates participant performance. A third EQA scheme for selected primary healthcare laboratories uses native patient split samples and evaluates the equivalence between POC and hospital MPs. The relationship between the three EQA schemes ispresented. The split sample EQA scheme provides a link between the hospital scheme and the scheme for primary healthcare. Results from 2017 to 2022 are presented for all three schemes. When aberrant EQA results occur Noklus takes actions to be able to have a sustainable equivalence between INR results. All three EQA schemes are important for monitoring the harmonization of INR results in Norway. This quality assurance system, including help and guidance of the participants, will reduce the risk of harm to patients due to non-equivalence of results from different MPs.

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.

Effect of Time and Temperature Variables on Prothrombin Time and International Normalized Ratio of Plasma in Patients in Gampaha, Sri Lanka

Generating accurate results for Prothrombin time (PT) and International Normalized Ratio (INR), PT/INR test is paramount in treatment monitoring. The diagnosis process measures how long it takes blood to clot. The main objective of this study was to determine the effect of storage time and temperature variables on PT and INR results in patients attending Hematologic clinics in Sri Lanka. This cross-sectional study was conducted during June and July 2021. PT was measured in the plasma samples, stored at different temperatures at baseline (0 hours), and then after 12 hours, 18 hours, and 24 hours after specimen collection. INR was calculated from each result, and the deviation percentage of PT and INR was calculated compared to the baseline result (0 hours). Then PT and INR percentage deviation is grouped as &lt;10% and &gt;10% to find biologically significant variations while paired t-test was performed to find statistical significance using GraphPad prism 8.4.3. At refrigerated temperature, both PT and INR results showed&gt;10% variation once kept 24 hours, and this variation was statistically significant (p&lt;0.01, Wilcoxon matched paired sign ranked test). The plasma specimens kept at laboratory temperature and specimen collection room temperature for 18 hours indicated &gt;10% variation of PT and INR values, while these variations were significant at the same criteria above. These results suggest that the separated plasma could only be recommended to test up to 12 hours. Therefore, the laboratories that operate in the same climatic conditions can now use these results to plan the specimen collection accordingly.

215 Fixed-dose vs. Weight-Based 4-Factor Prothrombin Complex Concentrate Dosing for Reversal of Warfarin-induced Intracranial Hemorrhage

215 Fixed-dose vs. Weight-Based 4-Factor Prothrombin Complex Concentrate Dosing for Reversal of Warfarin-induced Intracranial Hemorrhage

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

IntroductionPatients 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 methodsWe 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. ResultsA 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. ConclusionsThe 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.

Assessment of Anticoagulation Control Association with Warfarin Knowledge and Demographic Features of Iranian Population

Background: Warfarin is the most commonly used oral anticoagulant for patients with atrial fibrillation, prosthetic heart valves, and deep vein thrombosis with a narrow therapeutic index. Due to the importance of patients’ adherence to treatment and also regular measurements of International normalized ratio (INR), this can have a significant impact on the quality of anticoagulation control. Objectives: The primary aim of this study was to assess the association between warfarin knowledge and time in therapeutic range (TTR) in patients on warfarin anticoagulation for at least 6 months who were referred to anticoagulation clinic in Rajaie Heart Center during 2016 - 2017. Methods: In this cross-sectional study, 620 patients who had been referred to the outpatient Rajaie Hospital anticoagulant clinic and had been taking warfarin for over six months were asked to fill two questionnaires named anticoagulation knowledge assessment (AKA) during a 12-week period. After obtaining the necessary permits, TTR (by Rosendal method) was calculated using the INR results of patients. Results: A total of 620 patients completed the questionnaire. The relation between warfarin knowledge and anticoagulation control was not significant. The mean age of the study population was 52.45 SD ± 14.01 years. This study showed a significant relationship between TTR, duration of warfarin usage (PV = 0.03) and the underlying cause of this usage (PV = 0.016). Conclusions: Prevention of chronic diseases is one of the most important priorities of the health care systems. Reduction in complications such as thrombosis and bleeding can be achieved by efforts to promote patient’s knowledge. By recognition of relation between warfarin knowledge and social and demographic indicators, patient’s education gap can be detected and also planned for dissolving. This study showed that although many of the patients visited in anticoagulation clinic have poor anticoagulation control, but a major part of them have good knowledge of warfarin usage.

A Comparison of International Normalized Ratio Results by Point-of-Care Device and Clinical Laboratory Analyzers in a Vascular Surgery Department

A Comparison of International Normalized Ratio Results by Point-of-Care Device and Clinical Laboratory Analyzers in a Vascular Surgery Department

Clinical Impact of COVID-19 on Anticoagulation Management at the William S. Middleton Memorial Veterans Hospital

BACKGROUNDThe COVID-19 pandemic has extensively impacted the delivery of routine medical care including anticoagulation management. The Veterans Affairs Clinical Pharmacy Practice Office (VA CPPO) has provided guidance to assist anticoagulation clinic providers in developing action plans to determine the risk vs benefit of delaying routine monitoring to reduce patient risk of COVID-19 exposure in the health care system.Frequent laboratory monitoring of the International Normalized Ratio (INR) is needed to reduce the risk of bleeding and thromboembolic events for patients on warfarin. The Madison VA standard of care (SOC) includes routine INR monitoring at least every 6 weeks for stable patients taking warfarin. Alternatively, the benefit of routine laboratory monitoring for direct oral anticoagulants (DOACs) is less clear. Currently, the Madison VA recommends a complete blood count (CBC), serum creatinine (SCr), and liver function tests (LFTs) within 30 days prior to DOAC initiation, repeat CBC +/- SCr 1-3 months after DOAC initiation, then CBC/SCr every 6-12 months, monitored via the VA DOAC population management tool (PMT).Per the 2012 American Society of Hematology (ASH) and the American College of Chest Physicians (CHEST) guidelines, for warfarin, 12-week follow-up may be considered in patients with chronically stable INRs (Kearon et. al. Chest 2012). Additionally, the Madison VA completed a prior prospective study of 12-week INR follow-up for patients taking warfarin which demonstrated safety of extended follow-up intervals. However, the number of participants able to achieve (56%) and maintain (34%) a 12-week INR follow-up were lower than anticipated (Porter et. al. J Thromb Thrombolysis 2016).As of 3/30/2020, the Madison VA anticoagulation clinic followed 783 patients for warfarin management and 1742 patients for DOAC management.STUDY DESIGN AND METHODSA retrospective chart review to assess practice changes during the COVID-19 pandemic was conducted on anticoagulation patients with visits from 3/16/20 and 6/18/20 who were either on warfarin, transitioned to a DOAC, or newly initiated on DOAC therapy.For patients on warfarin with 2 therapeutic INRs obtained at least 4 weeks apart, follow-up was extended to 8-12 weeks. Conversion to a DOAC was considered for eligible warfarin patients, excluding presence of mechanical heart valves, moderate to severe mitral valve stenosis, significant liver disease (Child Pugh C), or pregnancy/breastfeeding. As there are no accepted standards for DOAC laboratory monitoring, per the VA CPPO, stable baseline labs within the prior 6-12 months were acceptable. Routine laboratory monitoring after initiation could also be deferred and patients were transitioned to the DOAC PMT.The data collected in the retrospective study was analyzed using descriptive statistics.OBJECTIVESThe objective of this study was to assess patient safety and INR stability using the proposed COVID-19 extended follow-up parameters. If patient safety and stability could be maintained, it may lead to long term practice changes to extend follow-up and improve the anticoagulation clinic workload efficiency.ENDPOINTSThe primary endpoint of the warfarin intervention was to determine the percentage of warfarin patients with therapeutic INRs after an extended interval. Secondary endpoints included the average length of the extended interval, bleeding or thromboembolic events during extended interval or within 30 days after the extended INR result. Other secondary endpoints included review of patient misadventures during the extended interval (e.g. patient taking incorrect warfarin doses), the percentage of patients with phone follow-up between extended INRs, and clinic time in therapeutic range (TTR).The primary endpoint of the DOAC transition intervention was to determine the percentage of warfarin patients transitioned to DOACs during the specified timeframe. Secondary endpoints included the average time since last CBC/SCr for those transitioning from warfarin or newly initiating DOAC, percentage of patients without an INR at time of transition, and bleeding or thromboembolic events within 30 days of transition.DisclosuresNo relevant conflicts of interest to declare.

Building a predictive model for warfarin dosing via machine learning

Abstract Background Warfarin titration via International Normalised Ratio (INR) monitoring can be a challenge for patients on long term anticoagulation due to its multiple drug interactions, long half life and patient's individual reponse, yet critically important due to its narrow therapeutic index. Machine learning may have a role in learning and replicating existing warfarin prescribing practices, to be potentially incorporated into an automated warfarin titration model. Purpose We aim to explore the feasibility of using machine learning to develop a model that can learn and predict actual warfarin titration practices. Methods A retrospective dataset of 4,247 patients with 48,895 data points of INR values were obtained from our institutional database. Patients who had less than 5 visits recorded, invalid or missing values were excluded. Variables studied included age, warfarin indication, warfarin dose, target INR range, actual INR values, time between titration and time in therapeutic range (TTR as defined by the Rosenthal formula). The machine learning model was developed on an unbiased training data set (1,805 patients), further refined on a handpicked balanced validation set (400 patients), before being evaluated on two balanced test sets of 100 patients each. The test sets were handpicked based on the criteria of TTR (“in vs out of range”) and stability of INR results (“low vs high fluctuation”) (Table 1). Given the time series nature of the data, a Recurrent Neural Network (RNN) was chosen to learn warfarin prescription practices. Long-short term memory (LSTM) cells were further employed to address the problem of time gaps between warfarin titration visits which could result in vanishing gradients. Results A total of 2,163 patients with 42,622 data points were studied (mean age 65±11.7 years, 54.7% male). The mean TTR was 65.4%. The total warfarin dose per week as predicted by the RNN was compared with actual total warfarin dose per week prescribed for each patient in the test sets. The coefficient of determination for the RNN in the “in vs out of range” and “low vs high fluctuation” test sets were 0.941 and 0.962 respectively (Figure 1). Conclusion This proof of concept study demonstrated that a RNN based machine learning model was able to learn and predict warfarin dosage changes with reasonable accuracy. The findings merit further evaluation of the potential use of machine learning in an automated warfarin titration model. Funding Acknowledgement Type of funding source: None