Warfarin-related Adverse Events Research Articles

Implementation and Outcome of Clinical Pharmacist-led Anticoagulation Clinic at Cardiac Center: A Retrospective Cohort Study

Abstract Context: Managing patients on anticoagulant therapy, such as warfarin, can be challenging due to various factors. Implementing a specialized care model can be a useful strategy to address this issue. Studies have demonstrated that pharmacist-led anticoagulation therapy leads to improved outcomes. Aims: We aimed to assess the anticoagulation quality of warfarin therapy achieved by the implementation of a Clinical Pharmacist-led Anticoagulation Clinic at a cardiac center. Materials and Methods: In conjunction with the cardiac center, the hospital’s pharmaceutical care department established a clinic. The anticoagulation quality was evaluated by determining the time in the therapeutic range (TTR), which was calculated using the Rosendaal method. Data were collected from February 1, 2021, to July 31, 2022, in a retrospective manner. Statistical Analysis Used: Both descriptive and inferential analyses were performed and are presented as counts, percentages, and means ± standard deviation, as appropriate. A paired t test was used to compare the mean TTR, and the outcomes were logistically regressed against candidate factors. Statistical significance was set at P < 0.05. Results: A total of 66 patients were eligible for inclusion in the study. The mean TTR was 73.4% ± 21.1%, compared to 46.9% ± 29.5% before clinic implementation. After clinic implementation, the proportion of patients who were able to reach a TTR of ≥70% increased from 28.8% to 60.6%. During clinical pharmacist care, there was one major bleeding event (0.7%/year), nine minor bleeding events (6%/year), and one thromboembolic event (0.7%/year). Age, comorbidities, and warfarin dose were not found to affect the TTR. However, females had a reduced likelihood of a TTR ≥70% (95% confidence interval, 0.11–0.89; P = 0.029). Conclusions: A clinical pharmacist-led anticoagulation clinic was implemented successfully, which resulted in positive outcomes in patient care by achieving a good TTR (≥70%) and low warfarin-related adverse events.

Severity and Hospitalization Cost Related to Warfarin-Related Adverse Events in a Tertiary Malaysian Hospital.

Introduction: Oral anticoagulant is essential for the treatment and prevention of thromboembolism. Warfarin is an effective oral anticoagulant in prevention and treatment of thromboembolism. However, warfarin is frequently associated with adverse event (AE) requiring hospitalization. Method: We performed a retrospective cohort study of all patients admitted to a large tertiary public hospital for warfarin-related AEs. Patients were grouped based on bleeding severity and the direct medical cost was also calculated. Results: During the 4 years study period, a total of 224 patients were admitted for warfarin-related AEs. Mean age of patients admitted was 65.1 years (standard deviation [SD] = 11.5). More than half, 59.6%, of them were on warfarin for prevention of stroke in atrial fibrillation or atrial flutter. Major bleeding occurred among 50.9% of the patients with gastrointestinal bleed, 34 (29.8%), as the common site of bleed. Patients with major bleed had longer median hospital stay of 4 days (interquartile range [IQR] = 5) compared to 3 (IQR = 3) days in non-major bleed. There were 17 (14.9%) death among the major bleeders. Mean medical cost for managing warfarin-related AEs was USD 708.08. Conclusion: The admitted patients were equally distributed in terms of bleeding severity. Medical cost incurred for managing warfarin-related AEs increased with the severity of bleeding.

Language proficiency and warfarin-related adverse events in older immigrants and Canadian residents: a population-based cohort study

Language proficiency and warfarin-related adverse events in older immigrants and Canadian residents: a population-based cohort study

Study on warfarin medication checklist for improving patient compliance

This study explored whether clinical pharmacists can improve patients' medication compliance with the use of warfarin medication checklist and the correlation between them. A total of 147 inpatients discharged from Shanghai Tongren Hospital with warfarin from July 2018 to September 2019 were randomly divided into the control group and the intervention group by random number table, including 75 in the control group and 72 in the intervention group. There were no statistically significant differences in gender, age, marital status, drinking history, smoking history, department distribution, type of thromboembolic disease, comorbidity and combined medication between the two groups (P>0.05). The control group received routine warfarin medication education at discharge, while the intervention group received clinical pharmacist's assessment of bleeding risk and targeted medication education using warfarin medication checklist at discharge. The monitoring time and value of the international normalized ratio (INR) between the two groups during hospitalization and within 6 months after discharge were recorded, as well as warfarin-related adverse events. The Morisky Medication Adherence Scale was used to evaluate the medication compliance of patients in the two groups. Spearman correlation analysis was used to study the relationship between warfarin compliance and variables in the warfarin medication checklist. The intervention group had better follow-up regularity than the control group (χ²=34.3, P<0.001), and the medication compliance in the intervention group was better than that in the control group (χ²=38.6, P<0.001). There were significant correlations between warfarin compliance and duration of warfarin therapy (R=-0.275, P=0.027), number of comorbidities (R=-0.335, P=0.004), bleeding risk (R=-0.433, P<0.001). In conclusion, using warfarin medication checklist can improve patients' medication compliance. Patients' medication compliance was significantly negatively correlated with duration of warfarin therapy, number of comorbidities and bleeding risk. Clinical pharmaceutical care can improve the medication compliance of patients with warfarin, so as to improve the medication results, which may be helpful for the drug treatment of patients with chronic diseases.

Evaluation of Warfarin Use in Patients With Mental Health Conditions in a Rural Community Health Center System.

Background: Mental health conditions (MHCs) may affect a patient's ability to comply with requirements necessary for safe warfarin use. Objective: To describe warfarin control, defined as time in therapeutic range (TTR), for patients with and without MHCs receiving care through a pharmacist-driven anticoagulation service within a rural community health center system. Methods: Retrospective cohort study of patients on warfarin between January 1, 2014, and December 31, 2017. The primary study endpoint was TTR. Secondary endpoints were the number of international normalized ratios (INRs) per 30 days, percentage of INRs within, above, and below target range, and warfarin-related adverse events. Results: A total of 79 patients were included-37 with and 42 without MHCs. Patients were mostly male (n = 47; 59.5%) and prescribed warfarin for atrial fibrillation (n = 45; 57.0%). There were no differences in overall TTR between those with (59.6%; interquartile range = 41.8-73.4) versus without (63.4%; interquartile range = 46.7-73.6) MHCs (P = .542). Secondary outcomes showed no differences in the frequency or percentage of INRs in, above, or below target range (all P > .05). However, there were about twice as many hemorrhagic complications in the group with MHCs (27% vs 11.9%; P = .149). Conclusion: Patients with MHCs experienced no difference in overall TTR as compared to patients without MHCs. However, there was a non-statistically significant reduction in TTR, which would be consistent with limited existing data and demonstrates possible reproducibility to a rural, underserved patient population. Future research is needed to validate these outcomes.

Warfarin Pharmacogenomics in Diverse Populations

Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing.

Association Between Patient Knowledge of Anticoagulation, INR Control, and Warfarin-Related Adverse Events

Background: Whether the level of patient’s knowledge about warfarin plays any role in maintenance of therapeutic international normalized ratio (INR) is controversial. Several studies have looked at patients’ warfarin knowledge and the level of patients’ anticoagulation control (AC). Most studies had small numbers and did not use validated questionnaires. Objectives: To use the Oral Anticoagulation Knowledge (OAK) test to assess patients’ knowledge of AC and to examine associations between knowledge, INR, and adverse events. Methods: In this cross-sectional study, patients were asked to complete the OAK test. Data on clinical and demographic characteristics, INR values, and thrombosis or bleeding events during the preceding 1 year period were collected. Associations between OAK scores, patient characteristics, proportion of therapeutic INRs, and bleeding/thrombosis events were assessed. Results: A total of 225 patients completed the OAK test. Mean (SD) age was 70 (13.4) years, 53% were male, and 75% were on warfarin for &gt;3 years. Over the preceding year, 57.3% of INRs were therapeutic, and there were 22 bleeding and 6 thrombotic events. The mean OAK score was 12/20 (passing score = 15/20); 64% of patients failed the OAK test. Predictors of passing the OAK test were younger age ( P = .01) and higher level of education ( P = .03). There was no association between OAK score and proportion of therapeutic INRs, or OAK score and bleeding or thrombosis events. Conclusion: We used the OAK test to assess patients’ AC knowledge. Results suggests that while younger and more educated patients were more likely to pass the OAK test, the OAK test results may not predict INR control or occurrence of bleeding or thrombotic events.

Safety and Efficacy Outcomes of Home and Hospital Warfarin Management Within a Pediatric Anticoagulation Clinic.

The complexity of managing children with chronic disease has led to an increase in the use of long-term warfarin therapy. Time in therapeutic range (TTR) is the preferred method for determining efficacy and stability of warfarin management. This study aimed to determine the TTR achievement and incidence of adverse events among pediatric warfarin patients managed by an anticoagulation clinic over 12 months and to compare TTR achievement between patients self-testing (PST) at home and those monitored using routine methods. International normalized ratio (INR) results reported for 2012 for children currently having their warfarin therapy managed by a dedicated pediatric anticoagulation clinic were analyzed. Warfarin-related adverse events were recorded. A total of 164 patients were included. In total, 93 children performed PST and 71 children tested their INR at a hospital or pathology service. TTR achievement for the cohort was 67.1% (95% confidence interval, 64.4-69.7). A total of 69.2% of INR tests conducted at home were within the TTR compared with 64.3% of INR tests conducted at a hospital or pathology service (P=0.07). One major bleeding event occurred and there was 1 thrombotic episode. PST demonstrated noninferior warfarin stability compared with routine methods. Routine outcome evaluation of pediatric anticoagulation management within single institutions is necessary to confirm the success of such programs.

A descriptive evaluation of warfarin use in patients with pulmonary arterial hypertension

IntroductionAlthough warfarin is often recommended for pulmonary arterial hypertension (PAH) management to mitigate thrombotic risk and improve survival, limited information exists to guide anticoagulation therapy. The purpose of this study was to compare and contrast warfarin therapy monitoring requirements and outcomes in patients with PAH and atrial fibrillation (AF) receiving long-term anticoagulation. Materials and MethodsPatients initiated on warfarin for PAH between January 1, 2000 and December 31, 2008 were matched by warfarin initiation date (±90days), age (±5years), chronic disease score (±1 points), and sex to patients initiated for AF. The primary study endpoint was frequency of INR monitoring per 30days of observation. Secondary endpoints included indicators of INR control and warfarin-related adverse events. Results and ConclusionA total of 84 patients were included - 18 and 66 in the PAH and AF groups, respectively. Patients with PAH had a higher median rate of INR measurements per 30days compared to patients with AF (median=2.0, interquartile range [IQR]=1.5 – 2.3 vs. median=1.6, IQR=1.3 – 2.0, p=0.046). There were no differences between groups with respect to percent of INR measurements in range, overall time in therapeutic range (TTR), or warfarin-related adverse events (all p>0.05). Study results suggest that patients with PAH may be more difficult to manage as seen through more frequent INR monitoring. Potential management difficulties did not translate to a lower performance on indicators of INR control or increased risk of warfarin-related adverse events.

Patients' Knowledge Of Anticoagulation and Its Association With Clinical Characteristics, INR Control and Warfarin-Related Adverse Events

BackgroundWhether level of knowledge of anticoagulation (AC) among patients on warfarin plays a role in maintenance of therapeutic INR or in warfarin-related adverse events is controversial. Most studies conducted on this subject had small patient sample sizes and did not use validated questionnaires to assess patients' knowledge of AC. ObjectivesTo use the validated Oral Anticoagulation Knowledge (OAK) test (Zeolla MM, 2006) to assess knowledge of AC among patients attending a busy AC clinic, and to examine associations between level of knowledge, INR control and adverse events. We hypothesized that patients with higher OAK test scores (i.e. greater knowledge) would have better INR control (primary outcome) and fewer bleeding and thrombosis events (secondary outcomes). MethodsConsecutive patients who had been followed in our AC clinic (tertiary care, university-affiliated hospital, 20,000 patient-visits per year) for at least one year and consented to participate were asked to complete the OAK test. The OAK test is a 20-question multiple-choice questionnaire that assesses patients' knowledge of warfarin AC. A passing score is ≥15 correct responses. Patient charts were reviewed to obtain data on clinical and demographic characteristics, and information on INR values and any thrombosis or bleeding events during the preceding 1 year period. Associations between OAK scores and patient characteristics, INR control and bleeding/thrombosis events were assessed by chi-square and t-tests, as appropriate. ResultsAmong 252 patients screened for participation, 225 met the inclusion criteria and completed the OAK test. Mean (SD) age was 70 (13.4) years, 53% were male and 75% were on warfarin for >3 years. Indications for AC were atrial fibrillation in 65%, VTE in 8%, mechanical heart valve in 10%, and other in 19%. The mean OAK score was 12/20, and 64% failed the OAK test. Predictors of a pass score on the OAK test were younger age (p= 0.01) and higher level of education (p=0.03). Over the preceding year, 57.3% of INRs were therapeutic, 25.1% subtherapeutic and 17.4% supratherapeutic, and there were 22 bleeding events and 5 thrombosis events. There was no association between OAK score and INR control, or OAK score and bleeding or thrombosis events. ConclusionTo our knowledge, this is the first study to use the validated OAK test to assess patients' AC knowledge. We found that younger and more educated patients were more likely to pass the OAK test; however, OAK test result did not predict INR control or occurrence of bleeding or thrombotic events. The OAK test may not be sensitive enough to capture the standard of care practiced in different anticoagulation clinics (e.g. differences in teaching material, frequency of INR checks in stable patients). Also, for some patients, AC knowledge among their caretakers may be more important than self-knowledge. Further research is needed to assess the relationship between AC knowledge, INR control and adverse clinical outcomes. Disclosures:No relevant conflicts of interest to declare.

Assessment of Warfarin Dosing Requirements After Bariatric Surgery in Patients Requiring Long‐Term Warfarin Therapy

To quantify the change in weekly warfarin dose after bariatric surgery in patients requiring long-term warfarin therapy. Retrospective matched-cohort study. Anticoagulation management service in an integrated health care delivery system. Patients receiving long-term warfarin anticoagulation who underwent bariatric surgery between January 1, 1996, and December 31, 2010 (27 patients), were matched by date of surgery (±2years), age (±5years), and target international normalized ratio (INR) range to patients receiving long-term anticoagulation therapy who underwent other abdominal surgical procedures: cholecystectomy or endoscopic retrograde cholangiopancreatography (59 patients [control group]). The main end point was change in postoperative warfarin dose from baseline (preoperative dose), measured at weekly postoperative intervals from weeks 1 to 8 and again at months 3 and 6. After surgery, patients in the bariatric surgery group had statistically significant decreases in weekly warfarin doses compared with preoperative dose at all postoperative time points (week 1 dose vs preoperative dose, p<0.01; doses at all other time points vs preoperative dose, p<0.001), except at 6months (p>0.05). No statistically significant decreases in warfarin dose were detected at any postoperative time points in the control group. Twenty patients (74.1%) in the bariatric surgery group experienced a 20% or more decrease in weekly warfarin dose compared with 19 patients (32.2%) in the control group (p=0.004). No significant differences in warfarin-related adverse events were noted between groups. Weekly warfarin doses decreased in the immediate postoperative period in anticoagulated patients after bariatric surgery but returned to their preoperative doses after approximately 6months. A similar pattern was not observed in patients in the control group who underwent other types of abdominal surgery. Compared with preoperative anticoagulation control, this resulted in reduced anticoagulation control despite close INR monitoring. If a causal relationship between bariatric surgery and warfarin sensitivity is established in future research, developing and validating a postbariatric surgery warfarin-dosing algorithm would be valuable.

Rates of hemorrhage during warfarin therapy for atrial fibrillation

Although warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin. We conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS(2) score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism). We included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%-3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%-12.5%) per person-year in all patients and 16.7% (95% CI 14.3%-19.4%) per person-year among patients with a CHADS(2) scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged. In this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%-3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.

Use of warfarin in long-term care: a systematic review.

BackgroundThe use of warfarin in older patients requires special consideration because of concerns with comorbidities, interacting medications, and the risk of bleeding. Several studies have suggested that warfarin may be underused or inconsistently prescribed in long-term care (LTC); no published systematic review has evaluated warfarin use for stroke prevention in this setting. This review was conducted to summarize the body of published original research regarding the use of warfarin in the LTC population.MethodsA systematic literature search of the PubMed, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library was conducted from January 1985 to August 2010 to identify studies that reported warfarin use in LTC. Studies were grouped by (1) rates of warfarin use and prescribing patterns, (2) association of resident and institutional characteristics with warfarin prescribing, (3) prescriber attitudes and concerns about warfarin use, (4) warfarin management and monitoring, and (5) warfarin-related adverse events. Summaries of study findings and quality assessments of each study were developed.ResultsTwenty-two studies met the inclusion criteria for this review. Atrial fibrillation (AF) was the most common indication for warfarin use in LTC and use of warfarin for stroke survivors was common. Rates of warfarin use in AF were low in 5 studies, ranging from 17% to 57%. These usage rates were low even among residents with high stroke risk and low bleeding risk. Scored bleeding risk had no apparent association with warfarin use in AF. In physician surveys, factors associated with not prescribing warfarin included risk of falls, dementia, short life expectancy, and history of bleeding. International normalized ratio was in the target range approximately half of the time. The combined overall rate of warfarin-related adverse events and potential events was 25.5 per 100 resident months on warfarin therapy.ConclusionsAmong residents with AF, use of warfarin and maintenance of INR levels to prevent stroke appear to be suboptimal. Among prescribers, perceived challenges associated with warfarin therapy often outweigh its benefits. Further research is needed to explicitly consider the appropriate balancing of risks and benefits in this frail patient population.

Intensity of Anticoagulation with Warfarin and Risk of Adverse Events in Patients Presenting to the Emergency Department

The ability of patients receiving warfarin to maintain an international normalized ratio (INR) within the desired therapeutic range is important for both efficacy and risk of adverse events. It is unclear whether the desired INR is maintained in patients receiving warfarin who present to the emergency department (ED) and whether they have a higher rate of adverse events. To evaluate the intensity of anticoagulation with warfarin and the risk of bleeding and thromboembolic complications in patients in the ED. A prospective observational study was performed using a convenience sample of patients receiving warfarin and presenting to the ED over an 18-week period. Data were collected using a standardized form that included chief complaint, history of present illness, past medical history, medication history, and allergy status. Information from the physical examination, laboratory results, and other diagnostic tests obtained as part of routine assessment in the ED, was used as necessary. The primary outcome was the proportion of patients whose INR was within, above, or below the desired therapeutic range. Bleeding complications and thromboembolic events were recorded in an attempt to determine the relationship between the intensity of anticoagulation and adverse outcomes. Two hundred one patients were included, with a mean (SD) age of 74.0 (13.2) years; 53.7% were female. Primary indications for warfarin were atrial fibrillation (75.6%) and venous thromboembolic disease (14.9%). A therapeutic INR was observed in 88 patients (43.8%; 95% CI 37.1 to 50.7), while 45 patients (22.4%; 95% CI 17.2 to 28.7) and 68 patients (33.8%; 95% CI 27.6 to 40.6) had subtherapeutic and supratherapeutic INRs, respectively. Overall, there were 28 (18 major and 10 minor) bleeding complications (13.9%; 95% CI 9.8 to 19.4) and 4 thromboembolic events (2.0%; 95% CI 0.6 to 5.2). Among patients with a bleeding complication, 14 (50.0%) had a supratherapeutic INR, while 2 patients who experienced a thromboembolic event (50.0%) had a subtherapeutic INR. The majority of patients receiving warfarin on presentation to the ED had INRs outside the desired therapeutic range. By establishing the impact of warfarin-related adverse events in this population, focused interventions can be established in this setting to address factors that can be targeted to reduce these events.

A randomized controlled trial of genotype-based Coumadin initiation

PurposeA randomized controlled trial was conducted in patients initiating warfarin to determine whether algorithms that incorporate genotypes affecting warfarin metabolism and function, and Vitamin K metabolism improve prediction of therapeutic warfarin dose and anticoagulation management. MethodsA total of 230 patients were randomized to either a clinical arm where dosing algorithms considered only clinical information or an interventional arm where dosing algorithms used clinical and genotypic variables (CYP2C9, CYP4F2, and VKORC1). Subjects in the interventional arm were genotyped within 5 hours, and the initial dose was informed by genotype. Primary endpoints were absolute prediction error relative to therapeutic dose, and time in therapeutic target range during the first 14 days. Secondary endpoints included time to stable dose in therapeutic range, time to first international normalization ratio >4, and warfarin-related adverse events. ResultsThe model including genetics more accurately identified therapeutic dose twice as often as the clinical model (65.3% vs. 34.7%) (P < 0.0001). Patients in the interventional arm did not achieve greater time in therapeutic range. Study arms were similar regarding time to international normalization ratio >4 and adverse events. ConclusionGenotype-informed dosing clearly improved prediction of therapeutic dose beyond that available with clinical parameters. Genetic information did not affect time in therapeutic target range during the first 14 days of therapy. Current management practices with the vagaries in dose adjustment after warfarin initiation exert a strong influence on traditional clinical outcomes.

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.

A descriptive evaluation of warfarin use in patients receiving hospice or palliative care services

To describe and compare warfarin therapy use and outcomes between warfarin-receiving patients in hospice or palliative care (HPC) and not in HPC. This retrospective, matched analysis examined warfarin-receiving patients who did (study cohort) and did not receive (control cohort) HPC services between 2002 and 2005. The matched cohorts were compared on rates of international normalized ratio (INR) measurements, INR control, and warfarin-related adverse events. Included were 101 and 484 study and matched control patients, respectively. Study patients had a higher mean rate of INR measurements per 30 days (2.2 +/- 1.7 vs. 1.7 +/- 1.4, P = 0.001) and were more likely to be above and below target INR range (P < 0.05) than control patients. Differences between the cohorts in incidences of warfarin-related adverse events were not statistically significant (P > 0.05). Patients in HPC required more frequent INR monitoring but had similar risks for warfarin-related adverse events.

Home INR monitoring of oral anticoagulant therapy in children using the CoaguChek™ S point-of-care monitor and a robust education program

Introduction Management strategies such as self-monitoring of anticoagulant therapy have been reported with increased frequency. Whilst patient education is frequently mentioned, details regarding the educational interventions employed are scarce. This study aimed to improve the outcomes of home monitoring of warfarin therapy in children through the development and implementation of a robust intervention, based upon the PRECEDE model of education. Materials and methods Participating parents had to complete an intensive education and training program. After demonstrating practical and theoretical competency, parents commenced home monitoring. Every second scheduled home INR (H-INR) required a paired INR on the same day, obtained by a trained pathology collector (C-INR). Demographic and statistical outcome data was collected. Results Parental understanding of warfarin therapy improved significantly following the educational intervention ( p < 0.0001). 65.5% of H-INRs and 64.4% of C-INRs were within the target range (ns). Lin's correlation coefficient between H-INRs and C-INRs was 0.949. There were no warfarin-related adverse events. Conclusion This study demonstrated a significant improvement in parental knowledge following participation in a robust educational intervention. Furthermore, compared to previous reports in children, a greater level of correlation between home and hospital-based INRs was achieved by participating parents. The use of similar educational interventions may serve to improve the outcomes of similar management strategies.

Use of specific indicators to detect warfarin-related adverse events

The use of specific indicators, or "triggers," to identify adverse drug events (ADEs) associated with warfarin therapy is described. Automated triggers provided by laboratory and pharmacy data were used to identify potential ADEs associated with warfarin therapy among patients treated in the emergency room or admitted to six community hospitals between July 2002 and December 2003. The triggers consisted of an International Normalized Ratio (INR) of greater than 3.0 and pharmacy orders for vitamin K. Pharmacists reviewed the triggers monthly for clinical determination of ADEs during preintervention and postintervention periods. Interventions consisted of staff education and real-time adjustments in therapy. A 39% overall reduction in ADEs occurred between the preintervention and postintervention periods. Harmful ADEs declined by 70%. INRs of greater than 3.0 and vitamin K administration appeared to be reliable indicators of warfarin-associated ADEs, and detection with these indicators appeared to reduce ADEs when combined with appropriate interventions.

Reduction in Anticoagulation-Related Adverse Drug Events Using a Trigger-Based Methodology

An initiative was undertaken by Novant Health System to address warfarin-related adverse drug events (ADEs) using lab-based patient-specific International Normalized Ratio (INR) triggers and pharmacy-based patient-specific Vitamin K triggers. The goal was to reduce ADEs related to the use of warfarin in both the inpatient and outpatient settings. Process improvements and medication management protocols were developed for patients managed with warfarin anticoagulation. During each month's seven-day sampling period, the hospital information system generated the lab and pharmacy triggers, and the clinical pharmacists used these patient-specific triggers to identify the patient charts for review. All triggered charts were reviewed. Preliminary harm classification based on the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index was assigned by the clinical pharmacists and recorded for each patient. The system achieved reductions in ADEs related to warfarin administration on an inpatient management (45%) and outpatient management (52%) basis. Although based on inpatient facility-generated triggers, the initiative also served as a reasonable outpatient model, with improvements seen in the outpatient physician intervention groups.