International Normalized Ratio Goal Research Articles

A Randomized Controlled Trial of Empiric Warfarin Dose Reduction with the Initiation of Doxycycline Therapy

BackgroundWhen interacting medications, such as doxycycline, are initiated during warfarin therapy, one method to correct for non-therapeutic international normalized ratio (INR) is adjusting the warfarin dose, if necessary. Another approach is preemptive warfarin dose adjustment. This study's objective was to evaluate the utility of preemptive warfarin dose adjustment for preventing non-therapeutic INR following doxycycline-warfarin co-administration. MethodsPatients were randomized to either a 10% to 20% preemptive warfarin dose reduction (intervention) or reactive warfarin dose adjustment (control) within 72hours of warfarin-doxycycline co-administration. Subjects received a follow-up INR within 7days (index INR). Primary outcome was the occurrence of index INR≥1 point over the INR goal range upper limit. Secondary outcomes included INR control, purchases of prescription vitamin K, and warfarin-associated adverse events in the 30days after doxycycline initiation. ResultsTwenty and 17 patients comprised the intervention and control groups. The intervention group's warfarin dose was reduced by a median of 11%. More control patients (n=2) experienced an INR≥1 point over the INR goal range upper limit compared to intervention (n=0); however, the difference (12% vs. 0%) was not statistically significant (p=0.20). A higher percentage of intervention patients had subtherapeutic index INRs compared to control (35% vs. 6%, p<0.05). One patient from each group experienced warfarin-associated bleeding. No thromboembolic complications or vitamin K use were observed. ConclusionsFor warfarin patients initiating doxycycline therapy, preemptive warfarin dose reduction did not result in supratherapeutic INRs but increased the likelihood of subtherapeutic INRs compared to INR monitoring with reactive warfarin dose adjustment.

Mechanisms of Bleeding and Approach to Patients With Axial-Flow Left Ventricular Assist Devices

Axial-flow LVADs have become an integral tool in the management of end-stage heart failure. Consequently, nonsurgical bleeding has emerged as a major source of morbidity and mortality in this fragile population. The mechanisms responsible for these adverse events include acquired von Willebrand disease, GI tract angiodysplasia formation, impaired platelet aggregation, and overuse of anticoagulation therapy. Because of ongoing concerns for pump thrombosis and thromboembolic events, the thrombotic/bleeding paradigm has led to a difficult clinical dilemma for those managing patients treated with axial flow LVADs. As the field progresses, advances in the understanding of the pathological mechanisms underlying bleeding/thrombosis risk, careful risk stratification, and potential use of novel anticoagulants will all play a role in the management of the LVAD patient.

Complete resection of asymptomatic solitary right atrial metastasis from renal cell carcinoma without inferior vena cava involvement

pump speed to approach the lower operating limit of 1800 rpm. Implications include (1) lower accuracy of estimated flow at lower speeds, (2) less ability to correct suction conditions by lowering pump speed, and (3) increased potential for pump thrombosis or rotor instability. Second, the HeartWare HVAD inflow cannula length was designed for placement through the left ventricular apex and is not optimized for the right ventricle. Shortening the length of the inflow cannula to accommodate the shallower right ventricular cavity in the right ventricular outflow tract is achieved by placing additional felt rings under the fixation ring (Figure 2, B). Other locations that may potentially allow normalchestclosure includeplacementintotherightatrium or the diaphragmatic surface of the right ventricle. For this patient, the goals for pump flows were 3 to 4 L/min through the RVAD and 5 to 6 L/min through the LVAD. Anticoagulation strategy consisted of aspirin and warfarin sodium, with an international normalized ratio goal of 2 to 3. We were successful in this case; however, this is the first report of HeartWare HVAD use in the role of RAVD after HeartMate II implantation. Firm recommendations regarding the potential widespread applicability of this therapy are therefore limited.

INR goal attainment and oral anticoagulation knowledge of patients enrolled in an anticoagulation clinic in a Veterans Affairs medical center.

In January 2009, the Joint Commission implemented a National Patient Safety Goal (NPSG) for ambulatory care, NPSG 3E, intended to reduce harm associated with the use of anticoagulation therapy. The 2011 NPSG 3E encompasses 8 elements of performance, including requirements that each organization (a) provide education regarding anticoagulation therapy to staff, patients, and families and (b) evaluate its safety practices and take appropriate action to improve its practices. The Alvin C. York (ACY) outpatient anticoagulation clinic provides education to new patients and their families at the initial clinic visit, with follow-up reinforcement of education as needed throughout their care. To (a) assess the knowledge level of patients receiving warfarin therapy in an anticoagulation clinic using the validated Anticoagulation Knowledge Assessment (AKA) questionnaire and (b) examine the relationship between patient anticoagulation knowledge and anticoagulation control as measured by the international normalized ratio (INR). All ACY Veterans Affairs (VA) anticoagulation clinic patients seen during their routine visit within an 8-week recruitment period from February 2010 to April 2010 were asked to complete the AKA questionnaire. Upon voluntary consent, the questionnaire was completed by the patient either during the clinic visit or returned later by mail. Demographic and clinical data were manually extracted from the computerized patient record system and included age, gender, indication for and duration of anticoagulation therapy, goal INR range, and the 10 INR values preceding the date of consent. A passing score was defined as at least 21 correct responses on the 29-item AKA questionnaire (72.4% correct). Statistical analyses included comparisons of demographic and clinical characteristics for patients with passing versus failing scores, assessed with Pearson chi-square and Fisher's exact test, and bivariate analyses of INR control with anticoagulation knowledge, assessed with Spearman's rho correlation. INR control was defined by 3 outcome measures: number of INRs within therapeutic range, time in therapeutic range (TTR) calculated using the Rosendaal method, and standard deviation (SD) of INR values. Anticoagulation knowledge was assessed with 2 measures: total AKA score and count of correct answers to a subset of 15 AKA items deemed by the investigators to be relevant to INR control. Of 447 patients enrolled in the anticoagulation clinic, 260 consented to participate in the survey, of whom 185 patients completed the AKA instrument (n=171 [92.4%] by mail) and were successfully matched to patient record system data. 178 (96.2%) respondents were male with a mean (SD) age of 68 (10.1) years. The majority of patients were undergoing anticoagulation treatment for atrial fibrillation (n=113, 61.1%) or deep venous/pulmonary thromboembolism (n=48, 25.9%). The majority of patients had been treated with warfarin for at least 1 year (n=162, 87.6%). Most patients had goal INR ranges of 2.0 to 3.0 (n=166, 89.7%). Of the 185 patients who completed the questionnaire, 137 (74.1%) achieved a passing score. The mean (SD) AKA questionnaire score was 78.1% (12.1%). There were 8 questions that were answered correctly by less than 70% of patients and identified as potential deficiencies in patient education. For the 167 patients who had been on warfarin therapy for at least 6 months and had 10 previous INR values, there was no significant Spearman's rho correlation between total number of correct questionnaire responses and INR control, defined as the count of the 10 previous INR values within goal range (rho =-0.022, P=0.776), TTR (rho=0.015, P=0.848), and SD (rho=0.047, P=0.550). There was also no significant relationship between number of correct INR-relevant responses and INR control by any of the 3 outcome measures (count in range rho=0.033, P=0.676; TTR rho=0.067, P=0.388; and SD rho=-0.029, P=0.708). Although 74.1% of patients on long-term warfarin therapy achieved a passing score of at least 21 correct answers on the 29-question AKA instrument, there was no significant relationship between patient warfarin knowledge and INR control. Areas for improvement in patient education have been identified and procedures for educational modification are currently in development.

Empiric warfarin dose adjustment with prednisone therapy. A randomized, controlled trial

Typically, the international normalized ratio (INR) is monitored and warfarin dose adjusted, if necessary, to correct non-therapeutic INR after interacting medications, like prednisone, are initiated during warfarin therapy. Preemptively adjusting the warfarin dose is another approach. To evaluate the utility of preemptive warfarin dosage adjustment for preventing non-therapeutic INR following prednisone-warfarin co-administration. Patients were randomized to either a preemptive warfarin dose reduction between 10 and 20% (intervention) or reactive warfarin dose adjustment (control) within 72 h of warfarin-prednisone co-administration. Subjects received a follow-up INR within 7 days. Primary outcome was the occurrence of follow-up INR ≥ 1 point over the INR goal range upper limit. Secondary outcomes included INR control, purchases of prescription vitamin K, and warfarin-associated adverse events in the 30 days after prednisone initiation. Twenty and 17 patients comprised the intervention and control groups. The intervention group's warfarin dose was reduced by a median of 11.8%. More control patients (n = 5) experienced an INR ≥ 1 point over the INR goal range upper limit compared to intervention (n = 2); however, the actual difference (29.4 vs.10.0%) was not statistically significant (P = 0.21). A higher percentage of intervention patients had a subtherapeutic follow-up INR compared to control (40 vs. 5.9%, P = 0.02). One patient from each group experienced warfarin-associated bleeding. No thromboembolic complications or vitamin K purchases were observed. For patients initiating prednisone therapy, preemptive warfarin dose reduction resulted in a non-significant reduction in supratherapeutic INR but increased the likelihood of subtherapeutic INR compared to INR monitoring with reactive warfarin dose adjustment.

New Approaches to Stroke Prevention in Atrial Fibrillation

It is estimated that atrial fibrillation (AF) is responsible for almost 15% of all strokes. Several randomized clinical trials have demonstrated the superiority of adjusted-dose warfarin over aspirin for stroke prevention in AF patients, particularly in high-risk individuals. Current national guidelines from the American Heart Association/American Stroke Association recommend the use of adjusted-dose warfarin with an international normalized ratio goal of 2.0 to 3.0 for patients with ischemic stroke or transient ischemic attack with persistent or paroxysmal AF, and aspirin for those who cannot take oral anticoagulants. However, the use of warfarin may be challenging in some patients, and there is a need for alternative treatments. We describe alternative treatments for AF and provide an overview on emerging therapies.

Comparison of Two Different Models of Anticoagulation Management Services with Usual Medical Care

To evaluate the safety and economic impact of three models of anticoagulation management services: usual medical care, a nurse-managed service, and a pharmacist-managed service. Retrospective medical record review. An eight-county health care system in central New York State. Nine hundred ninety-six patients (age range 19-99 yrs) who were receiving warfarin therapy for at least 6 months and who had three or more international normalized ratio (INR) values reported during the 1-year study period; 489 patients (6243 INR values) were in the pharmacist-managed group, 307 patients (3618 INR values) were in the nurse-managed group, and 200 patients (3142 INR values) were in the usual care group. All INR measurements were performed by the central laboratory or by on-site point-of-care testing. Data were queried from calendar year 2003 for the usual care and nurse-managed services and calendar year 2006 for the pharmacist-managed service. Anticoagulation indication, INR goal, baseline characteristics, and rates and costs of hospitalization and emergency department visits directly related to anticoagulation therapy were extracted from the medical record. If the INR goal was not documented, a range was assigned as appropriate from the American College of Chest Physicians anticoagulation guidelines. Markers of anticoagulation control--time in range (percentage of time a patient is maintained within their therapeutic range) and percentage of INR values in range--were calculated for each study group. Baseline characteristics were similar among all study groups. The pharmacist-managed service yielded the lowest rates of hospitalization and emergency department visits, with hospitalizations reduced by 56% versus nurse-managed service and 61% versus usual care (p<0.01). Emergency department visits were reduced by 78% in both the nurse-managed and usual care models (p<0.002). Based on visit rates, the pharmacist-managed service averted $141,277.34 in hospitalization costs and $10,183.76 in emergency department visit costs versus the nurse-managed service and $95,579.08 in hospitalization costs and $5511.21 in emergency department costs compared with the usual care model. Pharmacist-managed anticoagulation management services reduced the rates of anticoagulation-related emergency department visits and hospitalizations, with significant financial impact. Based on results of this study, a collaborative clinic using pharmacists, nurses, and physicians may be the optimal structure for an anticoagulation management service, with these results verified in future prospective randomized studies.

International Normalized Ratio values in group versus individual appointments in a pharmacist-managed anticoagulation clinic

The clinical effectiveness of a group-visit model versus individual point-of-care visits is compared by International Normalized Ratio (INR) monitoring in a pharmacist-managed anticoagulation clinic. This study was a prospective, randomized, repeated-measures, two-group, intention-to-treat comparison and survey at a pharmacist-managed anticoagulation clinic in a managed-care ambulatory care setting. Patients were eligible for this study if they were taking warfarin therapy for at least 30 days, had a goal INR range, and provided consent. At a routine point-of-care visit, eligible patients were randomly invited to participate in group visits. The number of visits and INR values were documented prospectively for both groups during the 16-week study period. Of the 45 patients who consented and enrolled in group visits, 28 patients participated for the 16-week study period. The control group included 108 patients seen by a pharmacist for individual anticoagulation appointments. No significant difference in the percentage of INR values within the therapeutic range was detected between patients in the group-visit model versus patients receiving individual visits (59% versus 56.6%, respectively; p = 0.536). Seventy-three percent of INR values for patients who attended group visits were within +/- 0.2 of the desired INR range compared with 71.9% of those in the control group ( p = 0.994). In addition, 79% of group-visit patients were within the therapeutic range at their last clinic visit compared with 67% of patients who attended individual appointments (p = 0.225). Group visits were preferred by 51% (n = 38) of patients who completed the satisfaction survey. Of the 92 patients who declined group-visit participation, 36% indicated that the time of day that group visits were offered was inconvenient. There were no thromboembolic or hemorrhagic events documented in either group during the study period. Group visits in a pharmacist-managed anticoagulation clinic may provide a safe and effective alternative to individual appointments.

Prevention of Symptomatic Pulmonary Embolism in Patients Undergoing Total Hip or Knee Arthroplasty

This clinical practice guideline is based on a systematic review of published studies on the management of adult patients undergoing total hip replacement (THR) or total knee replacement (TKR) aimed specifically at preventing symptomatic pulmonary embolism (PE). The guideline emphasizes the need to assess the patient's risk for both PE and postoperative bleeding. Mechanical prophylaxis and early mobilization are recommended for all patients. Chemoprophylactic agents were evaluated using a systematic literature review. Forty-two studies met eligibility criteria, of which 23 included patients who had TKR and 25 included patients who had THR. The following statements summarize the recommendations for chemoprophylaxis: Patients at standard risk of both PE and major bleeding should be considered for aspirin, low-molecular-weight heparin (LMWH), synthetic pentasaccharides, or warfarin with an international normalized ratio (INR) goal of < or =2.0. Patients at elevated (above standard) risk of PE and at standard risk of major bleeding should be considered for LMWH, synthetic pentasaccharides, or warfarin with an INR goal of < or =2.0. Patients at standard risk of PE and at elevated (above standard) risk of major bleeding should be considered for aspirin, warfarin with an INR goal of < or =2.0, or none. Patients at elevated (above standard) risk of both PE and major bleeding should be considered for aspirin, warfarin with an INR goal of < or =2.0, or none.

Improving Anticoagulation Therapy Using Point-of-Care Testing and a Standardized Protocol

Many patients in primary care require anticoagulation with warfarin for the prevention of venous and systemic embolism. Achieving the goal international normalized ratio (INR) with warfarin is challenging. The purpose of this quality improvement initiative was to increase the proportion of patients taking warfarin with an INR value within the goal range. We included all patients identified on an anticoagulation log in the family medicine residency practice during 3 time periods: baseline, after point-of-care (POC) testing was initiated (intervention period 1), and after a standardized warfarin-dosing protocol was implemented (intervention period 2). Educational sessions were conducted during each intervention period. Measures included the frequency of INR monitoring and the percentage of office visits in which patients' values were within the goal INR range. Data were analyzed using descriptive statistics, the Student t test, and the chi2 test. At baseline, patients had an average of 2.6 INR tests performed, and 30.8% were within the INR goal range. Using POC testing, the frequency of monitoring increased to 4.3 INR tests per patient (P = .04), but the percentage of patients within the INR goal remained low at 32.1% (P=.88). When physicians implemented the standardized protocol to guide warfarin dosing, the frequency of testing was similar (3.8 tests per patient), but the percentage of patients within the INR goal increased to 45.9% (P<.04). POC testing increased the frequency of INR testing, and additional use of a standardized protocol for warfarin dosing increased the percentage of patients within the INR goal range. This model of anticoagulation management could be easily implemented in any family medicine office.

Examining Differences in Weekly Warfarin Dose in Patients With and Without Cancer

The incidence of thrombosis and bleeding is higher in patients with cancer receiving warfarin compared with low molecular weight heparins. Despite these findings, warfarin remains a commonly used treatment strategy for anticoagulation in patients with cancer secondary to several factors that limit the use of low molecular weight heparins. Determining the appropriate warfarin dose in cancer patients is challenging. The objective of our study is to compare the weekly warfarin dose in patients with and without cancer. In a retrospective analysis, the average weekly warfarin dose was compared for 63 subjects who 1) were treated for cancer while receiving warfarin (n = 21), 2) completed treatment for their cancer before starting warfarin (n = 21), and 3) received warfarin with no diagnosis of cancer (n = 21). The data were abstracted from the medical record from the date the subject started taking a stable dose of warfarin after the initial titration until the discontinuation of warfarin. No significant differences were observed in the mean weekly warfarin dose, but the dose demonstrated greater intrasubject variability for subjects in group 1 (group 1, 31 +/- 22% vs. 2, 19 +/- 11% and 3, 15 +/- 10%, P = 0.003). Subjects in group 1 also spent more time above their goal International Normalized Ratio (group 1, 30 +/- 21% vs. 2, 21 +/- 16% and 3, 15 +/- 16%, P = 0.038). The average weekly warfarin dose was similar for the three groups, but the results of this study suggest that patients with cancer receiving treatment for their cancer and anticoagulation with warfarin are more difficult to appropriately anticoagulate.

The Influence of Ethnicity on Warfarin Dosage Requirement

The optimal dose of warfarin varies among individuals, and the prediction of a maintenance dose is difficult. Ethnicity has been reported to influence warfarin dosing. To quantitate the influence of ethnicity on warfarin dose requirement. We conducted a retrospective cohort study at a university anticoagulation clinic to evaluate the influence of ethnicity on warfarin dose. Inclusion criteria included age > or = 18 years, target international normalized ratio (INR) 2-3, and warfarin management within the clinic for > or = 3 months with a minimum of 5 clinic visits. We collected clinical and demographic data including age, gender, weight, ethnicity, disease states, concomitant medications, indication, weekly warfarin dosage, and INR. To assess potential confounders, multivariate, repeated-measures regression analysis was used to identify and adjust for variables that may influence the maintenance dose of warfarin. Of the 345 patients who met the inclusion criteria, 27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2 to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36 mg (34 to 39), and African Americans 43 mg (39 to 47) (p < 0.001). Additional factors found to influence warfarin dose requirement included age, weight, concomitant use of amiodarone, and diagnosis of venous thromboembolism. Warfarin dose requirements vary across ethnic groups even when adjusted for confounding factors, suggesting that genetic variation contributes to interpatient variability.

A Feasibility Study of Continuing Dose-Reduced Warfarin for Invasive Procedures in Patients With High Thromboembolic Risk

The management of perioperative anticoagulation therapy for patients having a high risk of thromboembolism who are receiving long-term oral anticoagulant therapy is uncertain. The prevalent approach is to discontinue oral anticoagulation therapy and initiate heparin therapy. Another potential strategy is to continue oral anticoagulation therapy with a temporary adjustment of warfarin intensity to a preoperative international normalized ratio (INR) of 1.5 to 2.0. Such moderate-dose anticoagulation therapy with warfarin has been shown to be hemostatically safe yet effective in the prevention of thromboembolism after hip or knee replacement. Over an 11-year period (ie, 1993 to 2003), our hemostatic consultative service prospectively identified 100 consecutive patients for whom we continued warfarin therapy at adjusted doses during the perioperative period, targeting a goal for the INR of 1.5 to 2.0. Patients were assigned a score for venous thromboembolic risk as well as overall surgical risk using published instruments. Score assignment was based on what was deemed to be extremely high risk for thromboembolism in patients who were receiving long-term warfarin therapy. Although the patients were accrued prospectively, the final retrospective analysis was made after all patients were treated. The most common indication (62%) for high-risk assignment was a thromboembolic event within the past 6 months. The second most prevalent reason was prior postoperative venous thromboembolism (VTE) [11%]. Indications for long-term anticoagulation therapy were recent VTE (62%), inherited thrombophilia (7%), antiphospholipid syndrome (13%), mechanical heart valves (18%), and prior cerebrovascular accident (4%). The prevalence of inherited thrombophilia probably has been grossly underestimated, as neither factor V Leiden mutation nor prothrombin 20210 mutation had been described during the bulk of the accrual time. Most surgical procedures (58%) were significantly invasive (Johns Hopkins category 3 to 5). The mean INR values were 2.1 on the day prior to surgery (SD, 0.9594; range, 1.2 to 6.5; n = 65), 1.8 on the day of surgery (SD, 0.4899; range, 1.2 to 4.9; n = 75), and 1.8 on the first postoperative day (SD, 0.4436; range, 1.1 to 3.3; n = 70). Two patients had major bleeding, and four patients had minor bleeding. One patient developed deep venous thrombosis. Several weeks after surgery, one patient with a prosthetic heart valve died from an embolic stroke, which was associated with a failure to increase his anticoagulation to therapeutic levels. Moderate-intensity anticoagulant therapy with warfarin, targeting a goal INR of 1.5 to 2.0, appears to be a safe and feasible method for preventing thromboembolic complications in high-risk surgical patients who are receiving long-term oral anticoagulant therapy. This may be considered a reasonable method to afford thromboprophylaxis in highly selected patients who are occasionally seen in clinical practice. This observational study does not prove equality, let alone superiority, to other proposed methods of anticoagulation therapy.

Accuracy and Precision of the CoaguChek S versus Laboratory INRs in a Clinic

BACKGROUND:The CoaguChek S is the next-generation coagulation monitor for measuring the international normalized ratio (INR) that replaces the CoaguChek device. Studies are lacking comparing the CoaguChek S with local laboratory INR assessment to ensure its accuracy and precision for monitoring patients on anticoagulation.OBJECTIVE:To evaluate accuracy, precision, and technical ease-of-use of the CoaguChek S compared with laboratory measurements.METHODS:Accuracy was evaluated in 101 patients by parallel assessment of INRs (CoaguChek S and laboratory); precision was evaluated in 31 patients using duplicate INRs from CoaguChek S and laboratory and from liquid quality controls. Accuracy was determined using orthogonal regression, Bland—Altman plot, and clinical applicability (INRs discrepant in categorization of INR goal and resulting in different therapeutic decisions). Precision was examined by comparing mean difference ± SD between repeated INRs from CoaguChek S and laboratory, coefficient of variation (CV), and coefficient of repeatability (CR). The influence of low and elevated INRs on accuracy and precision was also examined. To assess ease-of-use of the monitor, the number of technical errors was recorded.RESULTS:The CoaguChek S significantly correlated to laboratory measurement (r = 0.93); 16.7% of INRs resulted in discrepant categorization and 24.5% would have required a different therapeutic plan. The CV and CR compared well between CoaguChek S and laboratory (6% vs. 4.9%; 0.455 vs. 0.346, respectively). When subgroups of INR values <4.0 and <3.0 were evaluated, the precision improved with both methods. Precision, based on liquid quality controls, was good (CV 4.6% = low-level; 3.3% = high-level). The CoaguChek S was found to have an error rate of 1.8%.CONCLUSIONS:The CoaguChek S is an accurate and precise alternative to laboratory assessment of the INR at values <4.0; it is an efficient device with a low likelihood of errors during testing.

54-Year-Old Man With Dyspnea and Abdominal Wall Bruising

54-Year-Old Man With Dyspnea and Abdominal Wall Bruising