International Normalized Ratio Units Research Articles

CoaguChek and Coag-Sense PT2 Meter Point of Care INR Device Validation

ObjectiveTo standardize international normalized ratio (INR) measurements and improve data integrity by enabling electronic result transmission for warfarin monitoring, two point-of-care (POC) devices were evaluated against an internal plasma INR reference method. MethodsA multicenter study was pursued (January 24, 2022, through October 19, 2022) to compare concordance of two commercially available POC devices, Coag-Sense PT2 Meter (Coag-Sense) and CoaguChek XS Pro and Plus devices (CoaguChek), against an internal plasma INR method among patients treated with warfarin. Bias and linear regression analysis were assessed for these devices including dosing decision accuracy compared with plasma INR reference. ResultsTwo hundred ninety-nine patients treated with warfarin across three Mayo Clinic sites agreed to participate. Atrial fibrillation (n=191, 63.9%), venous thromboembolism (n=65; 21.7%), and heart valve prosthesis (n=46; 15.4%) were common anticoagulant indications with a 2.5 INR target for 280 (93.6%) of patients. For the CoaguChek devices, 243 (81.3%) of values fell within 0.2 INR units with plasma INR referent and 285 (95.3%) within 0.4 units (R2=0.93). For the Coag-Sense device, 102 (34.1%) of values fell within 0.2 INR units and 180 (60.2%) within 0.4 INR units of plasma INR values, (R2=0.83; P<.0001). Using the plasma INR as the gold standard, appropriate dosing recommendations would have occurred for 292 (97.7%) of the CoaguChek and 244 (81.6%) of the Coag-Sense results. ConclusionCompared with a plasma referent, INR values obtained from the CoaguChek devices exhibited less systematic bias compared with Coag-Sense measures. This translates to a greater percentage of concordant management decisions between POC and laboratory INR methods.

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

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

Validation of a Point-of-Care Analyzer for Determining Anticoagulation Status During Air Transport

ObjectiveWe evaluated a point-of-care prothrombin time (PT)/international normalized ratio (INR) cartridge-based analyzer for its feasibility, accuracy, and value in critical care air transport. MethodsIn this prospective study, blood samples from 10 randomly selected adult patients were tested with the cartridge during transport to determine feasibility. The cartridge results were compared with the laboratory results for the same samples. Similarly, blood samples from an additional 20 randomly selected adult patients were tested to determine test accuracy. A chart review identified 110 adult patients with PT/INR cartridge results to determine the clinical value of those results. ResultsData from the first group of 10 patients showed that vibration did not affect use of the cartridge. The average bias between the 2 testing methods was 0.0 INR units. A comparison of the PT/INR cartridge results and the laboratory results from the group of 20 patients showed that 73% of the cartridge values were within 0.2 of the laboratory values, 83% were within 0.4, and 93% were within 0.6. Of the 110 patients whose charts showed PT/INR cartridge results, 23% received blood products (45 trauma patients and 65 medical patients). ConclusionThe PT/INR cartridge withstands the rigors of rotor wing transport and provides accurate, valuable results for making clinical decisions.

Reliability of CoaguChek Pro II Point of Care System in Outpatient Setting in Farwaniya Hospital, Kuwait

Point of care testing (POCT) coagulometers are widely used for international normalized ratio (INR) monitoring for patients on vitamin K antagonists (VKA) therapy. In our study, we investigated the accuracy and reliability of CoaguChek pro II (Roche Diagnostics) as an alternative for standard laboratory testing (SLT) by ACL TOP 500 top system in outpatient department setting. Methods: We enrolled a total of 174 INR results in our study which were measured by CoaguChek ProII and ACL TOP 500 top. The three arms of the study were: INR <3.5, 3.5-4.4, and ≥4.5. The results were compared using Passing Bablok regression analysis and Bland-Altman plot. The agreement between the two methods was further evaluated to demonstrate the impact on dosing decision. Furthermore, the degree of patient satisfaction with POCT in our INR clinic was assessed by participating in a survey. Results: The overall correlation of INR measurements between POCT and SLT in our study was strong (r = 0.95), however, the correlation between the two methods in the 3.5-4.4 arm was moderate (r = 0.502). The overall agreement between the two methods in all three arms of the study in terms of dosing decision was good (Kappa = 0.862), with only 12.6% of INR measurements showing a difference in dosing decision. Ninety-Seven percent of all INR values measured by CoaguChek Pro II within therapeutic range (INR<3.5) were within 0.5 INR units when compared to ACL TOP 500 Top. Furthermore, we concluded that more than 90% of the patients in our center were satisfied with the POC service. Conclusion: We concluded that POCT is a good alternative to SLT in INR values falling in therapeutic and supra-therapeutic ranges; however, additional comparative studies investigating the accuracy and reliability between the two methods for INR results between 3.5-4.4 will add to the current body of knowledge. Furthermore, the majority of patients were satisfied with the service provided in the POC INR clinic.

Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach.

To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels. Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between 2005 and 2013 (N = 121,962) was followed until the first qualifying prescription for the potential interacting drugs was evaluated. Sixteen sub-cohorts, one for each study drug, and a control sub-cohort of warfarin were ascertained. Short-term changes in INR levels were assessed by comparing INR values measured before and after initiation of the interacting drug with paired Student's t-test. We also evaluated the proportion of patients with INR values outside the therapeutic range (INR: 2-3). Miconazole use was associated with the highest mean increase in INR (+3.35), followed by amiodarone (+1.28), fluconazole (+0.79), metronidazole (+0.75) and nystatin (+0.65). After subtracting the natural INR variation observed in the control sub-cohort, supra-therapeutic levels (INR > 3) were found in 53.2% (miconazole), 45.5% (amiodarone), 23.3% (metronidazole), 23.2% (fluconazole) and 17.6% (nystatin) of patients initiating treatment with these drugs. Carbamazepine use was associated with a mean INR decrease of -0.63 and infra-therapeutic levels (INR < 2) were observed in 46.2% of patients initiating carbamazepine. For all other drugs, the change was small to moderate, in absolute INR units (+0.23 to +0.55) and in the proportion of patients with INR levels out of therapeutic range (<16%). Clinically potentially important interactions were observed in several study drugs. The majority of them, although confirmed, had little impact after adjusting for standard INR variability in the general population of warfarin users.

Usefulness of the Mortality in Severe Sepsis in the Emergency Department score in an urban tertiary care hospital

BackgroundThe Mortality in Severe Sepsis in the Emergency Department (MISSED) score is a newly proposed scoring system. The goal of this study is to determine if the MISSED score is generalizable to an urban tertiary care hospital. MethodsThis is a retrospective chart review conducted from July 2012 to June 2014. Inclusion criteria consisted of adult emergency department (ED) patients with severe sepsis, defined as lactate level 4mmol/L or greater. Demographics, lactate, international normalized ratio (INR), albumin, intensive care unit admission, and ED intubation were analyzed using χ2 test, t test, and logistic regression. The MISSED score was calculated using the variables albumin 27g/L or less, INR 1.3 or greater, and age 65years or older and analyzed using the area under the curve. The primary outcome was inhospital mortality. ResultsA total of 182 patients met inclusion criteria, and mortality was 32%. Patients in the mortality group had older age (58.1±17.2 vs 62.7±14.7; P=.07), higher lactate (5.9±2.7 vs 7.3±3.1; P<.01), lower albumin (34.3±8.3 vs 25.6±7.1; P<.0001), higher INR (1.4±0.6 vs 2.4±1.9; P<.0001), ED intubation (21% vs 56%; P<.0001), and intensive care unit admission (41% vs 78%; P<.0001). The regression model found that albumin of 27g/L or less (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.05-3.36), INR 1.3 or greater (OR, 8.3; 95% CI, 3.35-20.51), and ED intubation (OR, 5.6; 95% CI, 2.56-12.35) predicted mortality. The area under the curve for the MISSED score was 0.78 (95% CI, 0.73-0.85). ConclusionThe MISSED score is useful for predicting mortality in ED patients with severe sepsis.

Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome.

Because of the possible interference of antiphospholipid antibodies (APL) with the phospholipid component of thromboplastin reagents, concerns have been raised about the validity of international normalized ratio (INR) testing to monitor anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome (APS). To investigate the reliability of the INR, we determined the INR using various prothrombin time (PT) assays and compared the results with those of a chromogenic factor X (CFX) assay. The study cohort consisted of 40 APS patients and 100 APL-negative patients who were on anticoagulant therapy for reasons other than APS. The agreement (i.e. the percentage of patients with a difference ≤0.5 INR units) between the PT-derived INR and CFX-derived INR equivalents was only moderate in both patient groups. The best agreement with CFX-derived INR equivalents was observed for the Thromborel S reagent in APS patients (69.1%) and for Neoplastin Plus in APL-negative patients (72.0%). Regarding the results for the point-of-care system CoaguChek XS, an agreement between the INR and the CFX-derived INR equivalent was less frequently observed in the APS patients (55.6 vs. 67.8%; p = 0.050). When considering all 3058 pairs of INR tests within the international sensitivity index (ISI)-calibrated range of 1.5 to 4.5s, we did not observe a higher variability of INR values in either the APS patient group or the subgroup of APS patients positive for lupus coagulants compared with the APL-negative controls. In conclusion, monitoring vitamin K antagonists (VKA) therapy with laboratory INR measurements seems to be suitable for the majority of APS patients.

The international normalized ratio does not reflect bleeding risk in esophageal variceal hemorrhage.

Background/Aims:The international normalized ratio (INR) has not been validated as a predictor of bleeding risk in cirrhotics. The aim of this study was to determine whether elevation in the INR correlated with risk of esophageal variceal hemorrhage and whether correction of the INR prior to endoscopic therapy affects failure to control bleeding.Patients and Methods:Patient records were retrospectively reviewed from January 1, 2000 to December 31, 2010. Cases were cirrhotics admitted to the hospital due to bleeding esophageal varices. Controls were cirrhotics with a history of non-bleeding esophageal varices admitted with ascites or encephalopathy. All variceal bleeders were treated with octreotide, antibiotics, and band ligation. Failure to control bleeding was defined according to the Baveno V criteria.Results:We analyzed 74 cases and 74 controls. The mean INR at presentation was lower in those with bleeding varices compared to non-bleeders (1.61 vs 1.74, P = 0.03). Those with bleeding varices had higher serum sodium (136.1 vs 133.8, P = 0.02), lower hemoglobin (9.59 vs 11.0, P < 0.001), and lower total bilirubin (2.47 vs 5.50, P < 0.001). Multivariable logistic regression showed total bilirubin to inversely correlate with bleeding (OR = 0.74). Bleeders received a mean of 1.14 units of fresh frozen plasma (FFP) prior to endoscopy (range 0-11 units). Of the 14 patients (20%) with failure to control bleeding, median INR (1.8 vs 1.5, P = 0.02) and median units of FFP transfused (2 vs 0, P = 0.01) were higher than those with hemostasis after the initial endoscopy.Conclusions:The INR reflects liver dysfunction, not bleeding risk. Correction of INR with FFP has little effect on hemostasis.

Analysis Of Warfarin Drug-Drug Interactions With Antibiotics In The Ambulatory Care Setting

▪ BackgroundThe typical effect of antibiotic initiation on the international normalized ratio (INR) in a real-world, stable warfarin population has not been adequately described. In addition, the influence of acute illness on the risk of excessive anticoagulation is not known. MethodsThis retrospective, longitudinal cohort study evaluated patients who received stable warfarin therapy between January 1, 2005 and March 31, 2011. The protocol for patients receiving warfarin and initiating antibiotic therapy during the study time-frame was to continue the warfarin dose unchanged and measure an INR within 3 to 7 days. Patients who purchased an antibiotic (antibiotic group) were compared to those purchasing a warfarin refill (stable controls) and patients with upper respiratory infection who did not purchase an antibiotic (sick controls). Primary outcomes included the mean INR change between the last INR prior to study inclusion (pre-index INR) and the first follow-up INR as well as the percentage of patients with a follow-up INR ≥ 5.0. The influence of interaction mechanism on the risk of a follow-up INR ≥ 5.0 was evaluated and predictors of a follow-up INR ≥ 5.0 were identified. ResultsA total of 5905 (49.0%), 5579 (46.2%), and 570 (4.8%) patients were included in the antibiotic, stable control, and sick control groups, respectively. The mean age was 68.3 years and the median pre-index INR was 2.5 (IQR 2.2-2.9). The mean change in INR was greater in the antibiotic group compared to the stable and sick control groups (both p< 0.05) but the increase was not clinically relevant (i.e., mean increase was less than 0.1 INR units). There were 3.2%, 2.6%, and 1.2% of patients with a follow-up INR ≥ 5.0 in the antibiotic, sick, and stable groups respectively (antibiotics v. stable and sick v. stable p<0.001; antibiotics v. sick p=0.434). Antibiotics interfering with warfarin metabolism were more likely to result in a follow-up INR ≥ 5.0 (9.6%) than those disrupting Vitamin K synthesis (3.1%) and those without a known interaction with warfarin (2.1%) (p<0.01) (Table). Antibiotic use, acute illness, cancer diagnosis, elevated baseline INR, and female sex predicted a follow-up INR ≥ 5.0. ConclusionIn the absence of antibiotics, acute illness alone increases the risk of excessive anticoagulation in previously stable warfarin patients. The risk of an INR ≥ 5.0 was greatest among antibiotics interfering with warfarin metabolism. In addition to antibiotics and acute illness, patients with cancer, elevated baseline INR, and females were most susceptible to excessive anticoagulation. Disclosures:Hylek:Bayer: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Daiichi Sankyo: Consultancy; Johnson and Johnson: Consultancy; Pfizer: Consultancy. Garcia:Bristol-Myers Squibb: Consultancy; Pfizer: Consultancy; Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Consultancy; Roche Diagnostics: Consultancy; CSL Behring: Consultancy. Crowther:Asahi Kasai: Membership on an entity's Board of Directors or advisory committees; Baxter: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Speakers Bureau; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Consultancy; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Viropharma: Membership on an entity's Board of Directors or advisory committees.

Transiently Increased Variation Between a Point-of-Care and Laboratory INR Method After a Long Period of Correlation

To perform long-term comparison between laboratory Stago and Point-of-Care (POC) i-STAT methods for determining the international normalized ratio (INR). This was a multicenter method comparison of patient INR results and factors related to performance variance. For 5 years, the assays demonstrated close patient correlation within and above the 3.5 INR therapeutic range cutoff (bias, 0.23 INR units). Patient results above 3.5 INR were bimodal, with 60% demonstrating an i-STAT INR bias of less than 0.5. Several patient conditions were associated with the presence of a higher i-STAT bias. In year 6, a broader range i-STAT bias developed, increasing to 0.73 INR units. The increased bias persisted for 3 years, then returned to initial levels following i-STAT adjustments. The substantial increase in i-STAT bias after a long period of stability was partly corrected by renewed correlation to the international reference preparation. Additional assay drift is discussed in relation to thromboplastin reagents and other testing variables. This study emphasizes the need for continual laboratory correlation with POC devices and caution in using published comparisons.

Predicting Survival in Patients Receiving Continuous Flow Left Ventricular Assist Devices

The aim of this study was to derive and validate a model to predict survival in candidates for HeartMate II (HMII) (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) support. LVAD mortality risk prediction is important for candidate selection and communicating expectations to patients and clinicians. With the evolution of LVAD support, prior risk prediction models have become less valid. Patients enrolled into the HMII bridge to transplantation and destination therapy trials (N = 1,122) were randomly divided into derivation (DC) (n = 583) and validation cohorts (VC) (n = 539). Pre-operative candidate predictors of 90-day mortality were examined in the DC with logistic regression, from which the HMII Risk Score (HMRS) was derived. The HMRS was then applied to the VC. There were 149 (13%) deaths within 90 days. In the DC, mortality (n = 80) was higher in older patients (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1 to 1.7 per 10 years), those with greater hypoalbuminemia (OR: 0.49, 95% CI: 0.31 to 0.76 per mg/dl of albumin), renal dysfunction (OR: 2.1, 95% CI: 1.4 to 3.2 per mg/dl creatinine), coagulopathy (OR: 3.1, 95% CI: 1.7 to 5.8 per international normalized ratio unit), and in those receiving LVAD support at less experienced centers (OR: 2.2, 95% CI: 1.2 to 4.4 for <15 trial patients). Mortality in the DC low, medium, and high HMRS groups was 4%, 16%, and 29%, respectively (p < 0.001). In the VC, corresponding mortality was 8%, 11%, and 25%, respectively (p < 0.001). HMRS discrimination was good (area under the receiver-operating characteristic curve: 0.71, 95% CI: 0.66 to 0.75). The HMRS might be useful for mortality risk stratification in HMII candidates and may serve as an additional tool in the patient selection process.

An analysis of discrepancy between point-of-care and central laboratory international normalized ratio testing in ED patients with cerebrovascular disease

ObjectiveOur objective was to identify demographic, clinical, and operational variables associated with discrepancy between point-of-care (POC) and central laboratory international normalized ratio (INR) results in emergency department (ED) patients with acute cerebrovascular disease. MethodsWe conducted a retrospective, observational cohort study of a series of 637 patients with acute cerebrovascular disease over 30 months who underwent simultaneous POC, using the i-STAT POC analyzer (Abbott, Princeton, NJ), and central laboratory INR testing at ED presentation. Point-of-care INR results greater than ±0.25 INR units from the central laboratory INR value were considered discrepant. We analyzed potential predictors of POC INR discrepancy from demographic, clinical, and operational variables using multivariable logistic regression. We evaluated the change in POC INR discrepancy incidence over the study interval using analysis of variance methodology. ResultsThe final diagnoses of the 637 subjects were acute ischemic stroke (n=427), transient ischemic attack (n=105), and intracranial hemorrhage (n=105). Discrepant POC INR results occurred in 21.5% (137/637) of subjects. The mean bias between POC and central laboratory INR was 0.24 ± 0.69 (range, 0-11.3). Significant covariates of POC INR discrepancy were oral anticoagulant use (odds ratio, 3.03; confidence interval, 1.37-6.68) and increasing activated partial thromboplastin time (aPTT) (odds ratio, 1.07; confidence interval, 1.02-1.12). We observed a significant reduction trend in the incidence of POC-central laboratory discrepancy over the study period, decreasing on average at 0.42% per month (F=5.59, P=.025). ConclusionIn this retrospective study, oral anticoagulant use and increasing aPTT were significantly associated with POC INR discrepancy in ED patients with acute cerebrovascular disease. Point-of-care INR discrepancy incidence decreased over the study interval.

Incidence of thromboembolic complications in patients with atrial fibrillation or mechanical heart valves with a subtherapeutic international normalized ratio: A prospective multicenter cohort study

Subtherapeutic international normalized ratio (INR) is frequently encountered in clinical practice, and patients with high-risk atrial fibrillation (AF) and with mechanical heart valve (MHV) with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events (TE). However, there are no prospective data evaluating this risk. Consecutive patients with a history of stable anticoagulation, but with a subtherapeutic INR, were prospectively included. Data on use and dose of low-molecular weight heparin (LMWH) bridging therapy were collected. The incidence of objectively confirmed TE and of major bleeding events within 90 days after the index INR was assessed. Five hundred and one patients with INR value 0.5-1 INR units below the lower limit of the patient-specific target INR were included in the study (280 with MHV and 221 with AF and CHADS2 score ≥3). LMWH was prescribed for 64 patients (12.8%). During follow-up, seven patients had a TE (1.40%; 95% confidence interval 0.68, 2.86%; 5.58 events for 100 patients year). All the events occurred within 14 days after the index INR. When we consider only patients who did not receive bridging therapy, the incidence of TE was 1.14% (5 of 437 patients; 95% confidence interval 0.49, 2.64%; 4.58 events for 100 patients year). There were no major bleeding events. The risk of TE in this population was not negligible. Given the frequent observation of subtherapeutic INR levels when monitoring vitamin K antagonists, this finding warrants additional investigation to improve the management of these patients.

Abstract P260: Superior Oral Anticoagulation Management With Self Testing and Automated Online Management; An Interim Analysis

Background: The safety and efficacy of warfarin therapy is critically dependent on control of the international normalized ratio (INR). One-third of 3,587 warfarin-treated patients with their INR time in the therapeutic range (TTR)&gt; 75% had a 50% lower major event rate compared to the one-third whose TTR was &lt; 60%. Objective: Assess the impact of three interventions on INR control and management time. Interventions included weekly INR self testing, daily low dose vitamin K, and online management. Methods: Sixty-three patients who were at least 18 years of age, had completed at least 7 months of warfarin therapy, and did not have a diagnosis of antiphospholipid antibody or HIV/AIDS provided written informed consent. INR control was assessed for 6 months pre-study and for up to 12 months during the study. INR control was reported as %TTR, %TTR +/- 0.3 INR units, and % time at an INR below 1.5 or above 5. Clinician time required for each “virtual visit” was recorded and 1 minute was assigned for each automated visit. Results: Eight of 63 patients were excluded (4 withdrew consent the first week, 3 were early protocol violaters, and 1 had warfarin discontinued at study day 11). Fifty-five patients provided 26.83 patient-years of pre-study data during which the TTR was 56.83%, TTR +/-0.3 INR units was 82.55%, and time below 1.5 or above 5 was 2.41% and 0.09%, respectively. Of 54.14 patient-years of study data, TTR improved to 79.65% TTR, 93.57% for TTR +/-0.3 INR units, and 0.4% and 0.07% for time below an INR of 1.5 or above 5, respectively (see Table ). Clinician management required 8.94 minutes per 4 “virtual visits” per patient per month. Summary: Weekly INR self testing, daily low dose vitamin K, and online automated management improved the TTR by 22%; a degree of improvement that has been associated with a 50% reduction in stroke, heart attack, major bleeding, and death. INRs were rarely very far out of range and management required clinician time of less than 10 minutes per patient per month. INR Control Pre-Study vs Study Period End Point Pre-Study n=55, 26.83 patient-years Study, n=55, 54.14 patient-years % Time in Range 56.83 79.65 % Time in Range +/- 0.3 INR units 82.55 93.57 % Time INR &lt; 1.5 2.41 0.40 % Time INR &gt; 5 0.09 0.07 # (%) Patient with TTR &gt; 75% 11 (20) 39 (70.1) # (%) Patients with TTR +/- 0.3 INR &gt; 75% 17 (30.1) 55 (100) # (%) Patients with TTR &lt; 60 30 (54.5) 4 (7.3) # (%) Patients with TTR +/- 0.3 INR &lt; 60% 7 (12.7) 0 (0.0)

Effect of heart failure exacerbations on anticoagulation: A prospective, observational, pilot cohort study

Background: Some studies have suggested that heart failure (HF) is associated with excessive anticoagulation, but definitive data or data showing causation do not exist. Knowledge of risk factors for excessive anticoagulation is critical to manage warfarin therapy safely. Objective: This study characterized the relation between HF-associated hypervolemia and excessive anticoagulation in patients with HF taking chronic warfarin therapy. Methods: This was a prospective, observational pilot study conducted in a university-based HF clinic. Patients aged 18 to 85 years with HF and taking warfarin were enrolled and were observed for episodes of hypervolemia. Hypervolemia was determined based on multiple clinical factors, including patient-reported symptoms and physical examination. Anticoagulation was assessed longitudinally per standard of care by measurement of the international normalized ratio (INR). A x 2 analysis was used to determine whether hypervolemia was associated with an increased risk of excessive anticoagulation. Paired and unpaired t tests were used for ad hoc analyses. Results: Forty patients with 41 HF episodes who were taking warfarin were enrolled between December 2003 and July 2007. Mean (SD) age was 67.2 (11.1) years and mean weight was 218.5 (62.8) pounds; 29 patients (72.5%) were men and 34 (85.0%) were white. Most had systolic dysfunction (n = 26; 65.0%) and were taking warfarin for atrial fibrillation (n = 33; 82.5%); the mean weekly warfarin dose was 30.8 (17.5) mg. There were 41 evaluable hypervolemia episodes over a mean follow-up of 14.5 (9.0) months. The mean INR change during hypervolemia was −0.02 (0.82) INR unit ( P = NS vs baseline). No association was found between hypervolemia episodes and INR increases of >50% ( P = NS); the results remained nonsignificant for both diastolic and systolic HF when analyzed separately. There was no significant change from baseline INR between patients classified with mild, moderate, or severe hypervolemia or between patients classified according to New York Heart Association (NYHA) functional class (all, P = NS). Patients with NYHA class III had a lower weekly warfarin dose than those with NYHA class II (25.73 vs 31.75 mg; P < 0.01). Conclusion: Mild hypervolemia did not appear to be related to excessive anticoagulation in these patients with HF taking chronic warfarin therapy.

The reliability of point‐of‐care prothrombin time testing. A comparison of CoaguChek S® and XS® INR measurements with hospital laboratory monitoring

The development of point-of-care (POC) testing devices enables patients to test their own international normalized ratio (INR) at home. However, previous studies have shown that when compared with clinical laboratory values, statistically significant differences may occur between the two methods of INR measurement. The aim of this study was to evaluate the accuracy of the CoaguChek S and XS POC meters relative to clinical laboratory measurements. As part of a randomized, crossover patient self-testing (PST) study at Cork University Hospital, patients were randomized to 6 months PST or 6 months routine care by the anticoagulation management service. During the PST arm of the study, patients measured their INR at home using the CoaguChek S or XS POC meter. External quality control was performed at enrollment, 2 months and 4 months by comparing the POC measured INR with the laboratory determined value. One hundred and fifty-one patients provided 673 paired samples. Good correlation was shown between the two methods of determination (r = 0.91), however, statistically significant differences did occur. A Bland-Altman plot illustrated good agreement of INR values between 2.0 and 3.5 INR units but there was increasing disagreement as the INR rose above 3.5. Eighty-seven per cent of all dual measurements were within the recommended 0.5 INR units of each other. This study adds to the growing evidence that POC testing is a reliable and safe alternative to hospital laboratory monitoring but highlights the importance of external quality control when these devices are used for monitoring oral anticoagulation.

Correlation of Point-of-Care International Normalized Ratio to Laboratory International Normalized Ratio in Hemodialysis Patients Taking Warfarin

To determine whether point-of-care (POC) International Normalized Ratio (INR) test results correlate with plasma INR measures in intermittent hemodialysis (IHD) patients on warfarin. Anemia is thought to reduce the accuracy of POC INR assay results. Whether POC INR testing could be implemented for hemodialysis patients on chronic warfarin, who are often anemic despite hematopoietic therapy, has not been established. Thirty-seven chronic hemodialysis patients on warfarin contributed sets of three consecutive blood samples for INR comparison immediately before hemodialysis: one finger stick, two from hemodialysis access (arteriovenous graft, fistula, or catheter). POC INR testing was performed using CoaguChek S device. Anemia was defined as hematocrit < 32%. Pairwise comparison and correlation of 258 INR results showed high correlation for POC versus laboratory INR (r = 0.94; P < 0.001). Of these, 16 (6%) differed by >0.6 INR units, four (1.6%) differed by >0.8 INR units, and one differed by >1.0 INR units. Resulting pairwise correlation analyses between samples were: for anemic patients (0.96; P < 0.001), nonanemic patients (0.93; P < 0.001), and for those obtained from arteriovenous grafts (0.94; P < 0.001). POC INR samples from dialysis catheters correlated poorly with laboratory INR results. POC INR correlates well with plasma INR measures in IHD patients requiring chronic warfarin, and anemia did not influence this reliability. Blood sampling from finger stick or arteriovenous graft or fistula showed excellent correlation with laboratory INR, whereas sampling from dialysis catheters was unsatisfactory, likely from heparin contamination.

Accuracy of Capillary Whole Blood International Normalized Ratio on the CoaguChek S, CoaguChek XS, and i-STAT 1 Point-of-Care Analyzers

We evaluated the accuracy of capillary whole blood international normalized ratio (INR) on the CoaguChek S (Roche Diagnostics, Indianapolis, IN), CoaguChek XS (Roche Diagnostics), and i-STAT 1 (i-STAT, East Windsor, NJ) point-of-care (POC) analyzers compared with venous plasma INRs determined by a reference laboratory method. Overall agreement between POC and laboratory plasma INR was very good, with median bias between capillary whole blood and laboratory plasma INRs varying from 0.0 to -0.2 INR units on all devices. More than 90% of results on the CoaguChek XS and i-STAT 1 and 88% of CoaguChek S results were within 0.4 INR units of the reference laboratory method. The CoaguChek XS and i-STAT 1 demonstrated greater accuracy than the CoaguChek S as measured by the number of results that differed by more than 0.5 INR units from the reference method. Median bias between CoaguChek S capillary whole blood and laboratory plasma INRs changed over time, demonstrating the need for ongoing quality assurance measures for POC INR programs.

Clinically significant differences between point-of-care analysers and a standard analyser for monitoring the International Normalized Ratio in oral anticoagulant therapy: a multi-instrument evaluation in a hospital outpatient setting

The increasing number of patients requiring oral anticoagulant therapy has lead to an expansion in the use of point-of-care test (POCT) analysers for measuring the International Normalized Ratio (INR) for monitoring purposes. Availability of new technology inevitably leads to comparisons with standard methodologies, and studies to date have reached varying conclusions about the comparability of POCT INRs with conventional testing. We compared the performance of five POCT instruments (Hemochron Junior Signature, ProTime, CoaguChek S, INRatio and TAS) against Innovin thromboplastin on a Sysmex CA1500 automated analyser. The Hemochron Junior Signature, ProTime and CoaguChek S demonstrated strong correlation with the laboratory method (R2 > 0.94). These three analysers demonstrated higher percentages of paired results within 0.5 INR units (81.5, 92.0 and 74.0%, respectively); the INRatio and TAS demonstrated 54.2 and 62.2%, respectively. Within INR ranges of up to 2.0, 2.1-3.0, 3.1-4.0 and above 4.0, none of the POCT analysers demonstrated significant agreement with the standard method in every range. All POCT instruments showed a degree of bias and greater variation from the standard method at INR values above 3.0. These data indicate the potential for POCT analysers to generate INR values sufficiently different from conventional methods that they may impact on clinical decision-making.

Quality of oral anticoagulation in patients with atrial fibrillation: A cross-sectional study in general practice

Objective: To evaluate the quality of management of oral anticoagulation among patients on oral anticoagulation for atrial fibrillation, and to verify the relation between patient performance and the risk of an event due to therapy. Methods: In a retrospective cross-sectional study involving 66 general practices, international normalized ratio (INR) values obtained over a 6-mo period were analysed. All INR values were determined by a single clinical laboratory, and additional medical information was provided by GPs. Results: 395 patients were included in the study, with a mean age of 74±9.6 y. In total, 3111 INR values were obtained. The mean number of tests/month per patient was 2.7±4.3. A total of 49 728 d of therapy was evaluated. Fifty-three per cent of the day values were within 0.5 INR units of the target (and 69% within 0.75 INR units of the target). The incidence rate for major bleeding was 4.4/100 patient years (and 2.9/100 patient years for thromboembolic events). There was a significant relation between patient performance and the presence of an event (p=0.017), with an odds ratio of 2.8 (95% CI 1.3–6.3).Conclusion: The quality of oral anticoagulation in patients with atrial fibrillation is suboptimal. This is significantly related to an increased risk of haemorrhagic events.