International Normalized Ratio Measurements Research Articles

P763Home Monitoring is associated with fewer gastrointestinal bleeding events following ventricular assist device implantation

Abstract Introduction Patients (pts) treated with a continuous flow left ventricular assist device (LVAD) are at increased risk for both bleeding and thromboembolic events. Maintenance of oral anticoagulation (AC) in the therapeutic range is difficult to achieve. Hypothesis Increased frequency of international normalized ratio (INR) home monitoring (HM) decreases the incidence of gastrointestinal bleeding and thromboembolic events (stroke, pump thrombosis) compared to standard of care (SOC). Methods We analyzed the efficacy of outpatient AC monitoring in consecutive pts who underwent VAD implantation at our institution between 2008–2018. Time in therapeutic range (TTR) was defined as percent of time with INR 2.5–2.8. HM pts had biweekly INR measurements using the Coagucheck XS ROCHE, while SOC pts had INR measured every 1–3 weeks. Gastrointestinal bleeding (GIB) and thromboembolic events were assessed by retrospective blinded chart review. Logistic regression was used to model the impact of TTR on the risk of GIB and THROMB. Results There were 85 pts: 44 in HM and 40 in SC arm with similar characteristics. SOC patients were more likely to have ischemic cardiomyopathy (63% vs 30%, p=0.006) and an LVAD (60% vs 25%, p=0.002). The use of HM was associated with a 19.7% reduction in the risk of GIB (8.8% vs 28.5%, p=0.043) and a trend towards lower risk of THROMB (6.8% vs 14.9%, p=0.19). HM pts had significantly longer TTR (52±20% vs 39±22%, p=0.007). Each percentage increase in TTR was associated with a 5.2% decrease in the risk of GIB [Odds Ratio (OR) 0.95, 95% Confidence Interval (CI) 0.91–0.99, p=0.009] even after adjustment for aspirin use and monitoring duration (OR 0.95, 95% CI 0.91–0.99, p=0.020). There was a similar decrease in the risk of overall bleeding (OR 0.94, 95% CI 0.90–0.98, p=0.008). Conclusions Increased frequency of home INR monitoring achieved a higher TTR and was associated with a 20% reduction in risk of gastrointestinal bleeding.

P4765Men who live alone have poor anticoagulation control: results from Danish registries

Abstract Background Efficacy and safety of vitamin K antagonists (VKAs) depend on quality of anticoagulation control, usually measured as time in therapeutic range (TTR). Factors that predict low TTR on VKAs could be used to identify patients who might benefit from interventions, or who would be better treated with a non-VKA oral anticoagulant (NOAC). Patients living alone may have difficulties in taking their medications, managing their diets, or coming to clinic for monitoring. Purpose To assess influence of cohabitation status on TTR with VKA among men and women. Methods We identified all Danish patients with atrial fibrillation (AF) who initiated VKA between 1997 and 2012, and studied patients who had 6 months of continuous VKA use and international normalized ratio (INR) monitoring. Patients were divided according to sex and whether they lived alone or with others. We calculated TTR using the Rosendaal method, and INR variability using Fihns method. We used a linear regression model to test for associations between TTR and covariates, and adjusted for age, income, medications and comorbidities. Results We identified 4,772 AF patients with 6 months of continuous VKA use and INR monitoring. 713 (15%) were men living alone, 1,073 (23%) were women living alone, 2,164 (45%) were men not living alone and 822 (17%) were women not living alone. INR was measured a median of 11 (interquartile range 8–15) times during the 180 days of VKA use, but men who lived alone had 0.6 (95% confidence interval (CI): 0.2 to 1.2) fewer INR measurements during the period. Median TTR was lowest among men living alone (57.2%), followed by women living alone (58.8%), women not living alone (61.0%) and men not living alone (62.5%). After multivariable adjustment, men who lived alone had a 3.6% (CI −5.6 to −1.6) lower TTR compared with men not living alone, but women who lived alone did not have significantly lower TTR (P=0.80) compared with women not living alone. Living alone had significantly greater effect on TTR among men than among women (interaction P=0.02). Men living alone also had higher adjusted INR variability (0.2, CI 0.0 to 0.4) compared with men not living alone. Conclusion Living alone was significantly related to low quality of anticoagulation control among men, but not among women. Acknowledgement/Funding this study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research

Synthetic cannabinoid-associated coagulopathy secondary to long-acting anticoagulant rodenticides: Observational case series and management recommendations.

Synthetic cannabinoids have become increasingly popular drugs of abuse due to low cost and inability to detect these substances on routine drug screenings. In the United States, incidence of synthetic cannabinoid contamination with long-acting anticoagulant rodenticides (LAARs) resulting in coagulopathy and bleeding complications has been described.We sought to describe the natural history, management approach, and outcomes of bleeding secondary to synthetic cannabinoid-associated LAAR toxicity in an observational case series of patients evaluated at an urban academic medical system.We conducted an observational study of patients with suspected exposure to LAAR-contaminated synthetic cannabinoids and associated bleeding treated within the Johns Hopkins Health System.In this 16 subject cohort, hematuria was the most common bleeding symptom at presentation. The majority of the cohort (75%) had international normalized ratio (INR) > 9.6 at presentation. Of the 13 patients with brodifacoum testing, 12/13 (92%) were positive. Twelve patients (75%) had at least 1 INR value below 2 within 24 hours of the first INR measurement. Of this cohort, 1/16 (6%) died in hospital. The median length of hospital stay was 4 days, (interquartile range = 3-6). The average cost of pharmacological treatment for coagulopathy during inpatient hospitalization was $5300 (range, $2241-$8086).In patients presenting with unexplained coagulopathy it is important for emergency department providers to consider LAAR intoxication and consider formal testing for brodifacoum to assist with treatment planning. Use of a standardized management algorithm including intravenous/oral vitamin K, judicious use of blood products and close laboratory monitoring is essential to optimizing outcomes.

Association Between Warfarin Control Metrics and Atrial Fibrillation Outcomes in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation

Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range. To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events. In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019. Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range. Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models. A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk. Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

Elevated International Normalized Ratio (INR) is Associated With an Increased Risk of Intraventricular Hemorrhage in Extremely Preterm Infants.

The international normalized ratio (INR), a standardized method of reporting the prothrombin time, can be a surrogate marker of the vitamin K-dependent coagulation pathways. To evaluate the relationship between INR measurements in the first 48 hours of life and subsequent development of intraventricular hemorrhage (IVH) in extremely preterm infants. A single-center retrospective, observational cohort study of infants born at <28 weeks gestation. The main outcome measure was defined as the degree of IVH seen on cranial ultrasound examinations at day 7 postnatal age. Of 200 infants, 109 (mean gestational age, 25.2 wk [SD, 1.27]) had coagulation results available. Of 109, 26 developed IVH. Elevated INR was associated with increased risk of a severe IVH (odds ratio [OR] 6.50; 95% confidence interval [CI], 1.65-25.62; P=0.008) adjusted for gestation, birth weight, and sex. INR was significantly associated with severe IVH in infants who did not receive blood products (OR, 64.60; 95% CI, 1.35-3081.25; P=0.035), but not in those who did (OR, 2.93; 95% CI, 0.67-12.71; P=0.151) (Pinteraction=0.086). An elevated INR in the first 48 hours of life may be useful to identify preterm infants at risk of severe IVH and may guide strategies to prevent the development, or limit the extension, of IVH.

Cost of Healthcare Associated With Deep Vein Thrombosis in Patients Treated With Warfarin in Turkey: 2010-2013 Database Analysis of a Tertiary Care Center

ObjectivesTo evaluate the cost of healthcare with respect to the quality of anticoagulation in patients with deep vein thrombosis (DVT) treated with warfarin in daily practice via the database analysis of a tertiary care center in the period 2010 to 2013. MethodsOf 258 307 records in total, 42 582 unique patients with DVT and 32 012 patients with international normalized ratio (INR) measurements were included. Overall, 6720 unique patients with DVT diagnosis and one or more INR measurements were identified, and the records of 4377 out of 6720 unique patients were validated and included in the analysis data set. The cost analysis was based on direct medical costs from the payer’s perspective. Cost items were related to healthcare resource utilization (inpatient and outpatient services) during the study period, which provided a basis for calculation of per-patient, outpatient, inpatient, and total direct medical costs. ResultsMean outpatient, inpatient, and total hospital admission costs were $578, $2195, and $2785, respectively, for patients with time in the therapeutic range of 70% or more, whereas the same costs were $571, $2163, and $3192, respectively, for patients with time in the therapeutic range of less than 70%. ConclusionsOur findings for a retrospective cohort of patients with DVT undergoing warfarin therapy reveal that patients spent 70% or more, as opposed to less than 70%, of follow-up time within the therapeutic INR range and that outpatient care, as opposed to inpatient care, was associated with lower healthcare costs. Given the significant contribution that hospital stay makes to the cost burden of DVT, our findings also highlight the association between poor warfarin anticoagulant control and increased hospitalization costs.

Choosing between continuing vitamin K antagonists (VKA) or switching to a direct oral anticoagulant in currently well‐controlled patients on VKA for atrial fibrillation: a randomised controlled trial (GAInN)

Choosing between continuing vitamin K antagonists (<scp>VKA</scp>) or switching to a direct oral anticoagulant in currently well‐controlled patients on <scp>VKA</scp> for atrial fibrillation: a randomised controlled trial (<scp>GAI</scp>nN)

Time in therapeutic range and risk of thromboembolism and bleeding in patients with a mechanical heart valve prosthesis

ObjectiveOral anticoagulation with vitamin K antagonists is recommended after mechanical heart valve replacement. However, data regarding the association between the quality of vitamin K antagonist treatment and the risk of complications are sparse. MethodsPatients undergoing mechanical heart valve replacement (1997-2012) with available data on international normalized ratio values were identified in Danish registries. The quality of vitamin K antagonist treatment between discharge after valve replacement and 6 months postdischarge (ie, index) was assessed as time in therapeutic range (TTR) ≥70% or <70% reflecting the percentage of time in therapeutic international normalized ratio interval. Patients were followed from index until occurrence of an outcome of interest (ie, thromboembolism and bleeding), death, or end of study (December 31, 2012), whichever came first. The risk of outcomes according to quality of vitamin K antagonist treatment was estimated with multivariable Cox regression. ResultsIn total, 659 patients undergoing mechanical heart valve replacement were included in the study. Median number of international normalized ratio measurements in the 6-month period after surgery was 13 (interquartile range, 8-19). Median TTR was 54.9% (interquartile range, 39.0%-72.9%) and 29.1% of patients had a TTR ≥70%. Median follow-up was 6.1 years. The risk of thromboembolism was significantly lower in the group with TTR ≥70% compared with TTR <70% (hazard ratio, 0.44; 95% confidence interval, 0.22-0.85), whereas no significant difference concerning risk of bleeding among groups was found (hazard ratio, 0.63; 95% confidence interval 0.36-1.08). ConclusionsIn patients undergoing mechanical heart valve replacement, TTR <70% in the 6-month period after surgery was associated with an increased risk of thromboembolic events but not bleeding compared with TTR ≥70%.

Generational performance of three point-of-care testing devices compared with standard laboratory measurement of the international normalised ratio across extended ranges

Point-of-care testing (POCT) of the international normalised ratio (INR) is recognised as a rapid and reliable alternative to venous INR measurement for titration and monitoring of patients anticoagulated with vitamin...

Relevance of Polypharmacy for Clinical Outcome in Patients Receiving Vitamin K Antagonists.

Although polypharmacy is associated with a negative clinical outcome in various settings and commonly observed in patients receiving oral anticoagulation therapy, evidence on the relevance for the clinical outcome of anticoagulated patients is currently limited. The aim of the study was to investigate the effect of polypharmacy on the clinical outcomes among patients taking phenprocoumon. Prospective cohort study. Regular medical care. Information on 2011 individuals receiving vitamin K antagonists was available for analysis from the prospective multicenter thrombEVAL study. Data were obtained from clinical visits, computer-assisted interviews, and laboratory measurements. Information on clinical outcome was obtained during a 3-year follow-up period and subsequently validated via medical records. The prevalence of polypharmacy (five drugs or more) was 84.1% (n = 1691). Quality of anticoagulation therapy assessed by time in therapeutic range was lower in individuals on five to eight drugs and nine drugs or more (70.7% and 64.7%, respectively) compared with subjects without polypharmacy (73.4%). In addition, a significantly higher variability of international normalized ratio measurements was found in the presence of polypharmacy. The cumulative incidence of bleeding, hospitalization, and all-cause mortality, but not for thromboembolic events, increased across groups of medication. In adjusted Cox regression analysis, polypharmacy is an independent risk factor for bleeding (hazard ratio [HR]≥ 9 drugs vs 1-4 drugs = 1.62; 95% confidence interval [CI] = 1.04-2.52; p = .033); hospitalization (HR≥ 9 drugs vs 1-4 drugs = 1.60; 95% CI = 1.26-2.03; p < .001; and all-cause mortality (HR≥ 9 drugs vs 1-4 drugs = 2.16; 95% CI = 1.43-3.27; p < .001) in a dose-dependent relationship. Per additional drug, bleeding risk was increased by 4%. Polypharmacy influences the quality of anticoagulation therapy and translates into an elevated risk of adverse events in anticoagulated patients. This suggests that additional medication intake in such patients should be critically reviewed by physicians, and it highlights the importance of initiating investigations aimed at reducing multiple medication intake. J Am Geriatr Soc 67:463-470, 2019.

Impact of CYP2C9 and VKORC1 Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy.

Warfarin is an oral anticoagulant frequently used in the treatment of different cardiovascular diseases. Genetic polymorphisms in the CYP2C9 and VKORC1 genes have produced variants with altered catalytic properties. A total of 212 cardiovascular patients were genotyped for 17 Single Nucleotide Polymorphisms (SNPs) within the CYP2C9 and VKORC1 genes. This study confirmed a genetic association of the CYP2C9*3 and VKORC1 rs10871454, rs8050894, rs9934438, and rs17708472 SNPs with warfarin sensitivity. This study also found an association between CYP2C9 and VKORC1 genetic haplotype blocks and warfarin sensitivity. The initial warfarin dose was significantly related to the CYP2C9*3 polymorphism and the four VKORC1 SNPs (p < 0.001). There were significant associations between rs4086116 SNP and TAT haplotype within CYP2C9 gene and rs17708472 SNP and CCGG haplotype within VKORC1 gene and warfarin responsiveness. However, possessing a VKORC1 variant allele was found to affect the international normalized ratio (INR) outcomes during initiation of warfarin therapy. In contrast, there was a loose association between the CYP2C9 variant and INR measurements. These findings can enhance the current understanding of the great variability in response to warfarin treatment in Arabs.

International Analysis of LVAD Point-of-Care Versus Plasma INR: A Multicenter Study.

International normalized ratio (INR) measurements manage risks of bleeding and clotting sequelae in the population with left ventricular assist device (LVAD). Studies suggest that point-of-care (POC) INR does not significantly differ from plasma INR (P-INR) values in other patient populations, although this has not been validated in a multicenter LVAD study. We sought to determine whether POC-INR and P-INR values differ significantly in the LVAD population and reviewed patients with permanent LVAD implantation at seven institutions internationally. Our cohort comprised of 279 paired POC-INR and P-INR checks in patients supported on average 630 ± 598 days postimplant with predominately HeartWare, HeartMate II, and HeartMate III devices. The population averaged 57.9 years of age, and there were 86.7% male. We found no statistically significant difference between POC-INR and P-INR values. International normalized ratio accuracy correlated weakly with the time between INR measurements (p < 0.001). When the time difference was less than 4 hours, the difference between INR pairs was significantly lower than measurements greater than 8 hours (p = 0.006). There was no statistically significant difference when comparing paired INR values and time after implant to INR check (p = 0.43), age (p = 0.12), known coagulopathy (p = 0.12), bleeding history (p = 0.22), or thrombosis history (p = 0.34). This is the first large multicenter international study comparing POC-INR and P-INR measurements in patients with LVAD and found no statistically significant difference between either methods, particularly when measured within less than 4 hours of each other.

Reliability of the portable coagulometer qLabs to accurately measure the activated thromboplastin time and international normalized ratio: a prospective study in critically ill patients.

: The current prospective study was aimed at investigating whether a portable coagulometer (qLabs) can be used to reliably monitor activated thromboplastin time (aPTT) and international normalized ratio (INR) in critically ill patients, as compared with standard central laboratory measurement. Both precision and accuracy of INR and aPTT measured by qLabs were assessed in this observational study by finger prick group (N = 30 patients) and blood droplet group from central venous catheter drawn (N = 60). For accuracy, clinical agreement percentage was ±0.3 for INR and ±10 s for aPTT. Precision of INR measurement in qLabs showed excellent intraclass correlation coefficient (ICC > 90%). Precision of aPTT measurement in qLabs was less acceptable for both finger prick [ICC: 0.70; Bland-Altman plot: 2.2 s (-19.8, 24.2)] and blood droplet [ICC: 0.50; Bland-Altman plot: 0.4 s (-70.9, 71.8)] groups. Accuracy of qLabs was acceptable for INR assessment (clinical agreement 90 and 81%, for finger prick and blood droplet groups, respectively), but not for aPTT (clinical agreement 55 and 68%, respectively). Accuracy of finger prick and blood droplet measurements in qLabs was better for INR and aPTT values near-to-normal (1.2 and 37 s, respectively). INR values from qLabs were consistent with the 'gold standard'. qLabs measurement is only reliable for aPTT values near-to-normal.

Compliance with pathology testing guidelines in Australian general practice: protocol for a secondary analysis of electronic health record data

IntroductionIn Australia, general practitioners usually are the first point of contact for patients with non-urgent medical conditions. Appropriate and efficient utilisation of pathology tests by general practitioners forms a key...

The pediatric acenocoumarol dosing algorithm: the Children Anticoagulation and Pharmacogenetics Study

Background The large variability in dose requirement of vitaminK antagonists is well known. For warfarin, pediatric dosing algorithms have been developed to predict the correct dose for a patient;however,this is not the case for acenocoumarol. Objectives To develop dosing algorithms for pediatric patients receiving acenocoumarol with and without genetic information. Methods The Children Anticoagulation and Pharmacogenetics Study was designed as a multicenter retrospective follow-up study in Dutch anticoagulation clinics and children's hospitals. Pediatric patients who used acenocoumarol between 1995 and 2014 were selected for inclusion. Clinical information and saliva samples for genotyping of the genes encoding cytochromeP450 (CYP)2C9, vitaminK epoxide reductase complex subunit1 (VKORC1), CYP4F2, CYP2C18 and CYP3A4 were collected. Linear regression was used to analyze their association with the log mean stable dose. A stable period was defined as three or more consecutive International Normalized Ratio measurements within the therapeutic range over a period of ≥3weeks. Results In total, 175 patients were included in the study, of whom 86 had a stable period and no missing clinical information (clinical cohort; median age 8.9years, and 49% female). For 80 of these 86 patients, genetic information was also available (genetic cohort). The clinical algorithm, containing body surface area and indication, explained 45.0% of the variability in dose requirement of acenocoumarol. After addition of the VKORC1, CYP2C9, and CYP2C18 genotypes to the algorithm, this increased to 61.8%. Conclusions These findings show that clinical factors had the largest impact on the required dose of acenocoumarol in pediatric patients. Nevertheless, genetic factors, and especially VKORC1, also explained a significant part of the variability.

A prospective, multi-center cohort study: investigating the ability of warfarin-treated patients to predict their INR

In practice, warfarin-treated patients may share insight regarding their international normalized ratio (INR) value before it is measured. The accuracy and potential utility of these predictions have not been evaluated. To (1) test how accurately patients can predict their INR; (2) identify demographic factors associated with their ability to predict their INR accurately; and (3) identify demographic factors associated with the patient's INR being in the therapeutic range. A prospective, multi-center cohort study enrolled patients from eight anticoagulation clinics in Iowa. Inclusion criteria were: age ≥ 18years, warfarin use ≥ 60days, INR goal of 2.0-3.0, and expected warfarin use > 6months. Subjects completed a data collection form during enrollment and before each INR measurement. Data included demographics, a set of medication taking beliefs and practices, self-reported adherence, past INR values, INR prediction and reason(s) for the prediction. There were 87 subjects enrolled with 372 INR measurements. The mean (SD) number of INRs per subject was 4.3 (1.8). Thirty percent of subjects reported they could tell when their INR is out of goal range. Patients predicted that 90.5% of their INRs would be within goal range, although only 65.5% of INRs were therapeutic. Patients correctly predicted a low INR as low or high INR as high in only 9.4% of out of range instances. A set of demographic characteristics and medication beliefs were not associated with prediction accuracy or percentage of INR measurements in range (PINRR). Most patients did not give a reason for their predicted result. For those that did, the most common factor was perceived stability at current dose. While some patients believed they could predict when their INR was out of range, only few were able to do so. Most patients assumed a therapeutic INR and missed when their INR was high or low. Patients should be advised against modifying their warfarin dose without consulting the provider that manages their therapy. ClinicalTrials.gov number, NCT 02764112.

Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial

BackgroundGenotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved.MethodsAn open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy.ResultsAmong 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference −1.16, 90% CI −1.48 to −0.84, P < 0.001 for both non-inferiority and superiority). The percentage of time within the therapeutic range over 3 months and median time to stable international normalized ratio (INR) did not differ between the genotype-guided and traditional dosing groups. The frequency of dose titrations (incidence rate ratio 0.76, 95% CI 0.67 to 0.86, P = 0.001), but not frequency of INR measurements, was lower at 1, 2, and 3 months in the genotype-guided group. The proportions of patients who experienced minor or major bleeding, recurrent venous thromboembolism, or out-of-range INR did not differ between both arms. For predicting maintenance doses, the pharmacogenetic algorithm achieved an R2 = 42.4% (P < 0.001) and mean percentage error of −7.4%.ConclusionsAmong Asian adults commencing warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients.Trial registrationClinicalTrials.gov NCT00700895. Registered on June 19, 2008.

Renal function in patients with mechanical prosthetic valves : Long-term effects of anticoagulation and over-anticoagulation with warfarin.

Warfarin-related nephropathy (WRN) is acomplication of warfarin over-anticoagulation that is associated with acute and/or chronic renal dysfunction and increased mortality. The long-term effects of warfarin on renal function has not been adequately studied in patients with amechanical prosthetic valve (MPV). To study the time-dependent effects of over-anticoagulation on renal function in patients with aMPV. A total of 193 patients who underwent MPV implantation and were followed up in this study were eligible for inclusion. Time above therapeutic international normalized ratio (INR) range (TATR) was calculated by dividing the number of INR measurements above target in ayear by the total number of INR measurements within ayear. Patients were divided into quartiles according to average TATR at 60months. At 60months more patients within the 4thquartile had a ≥20% reduction in the estimated glomerular filtration rate (eGFR, 25.0%, p = 0.04) and chronic kidney disease (CKD, 33.0%, p = 0.07) compared to patients within the 1stquartile. High TATR remained asignificant determinant for reduction in eGFR (odds ratio OR:7.50, 95% confidence interval CI:1.55-36.32) and CKD (OR:5.15, 95% CI:1.26-20.62) after adjusting for other variables. Longitudinal analysis revealed that the change in eGFR was related to the duration of warfarin use (p < 0.001) and the interaction between the duration of warfarin use and TATR (p = 0.03). Similar findings were observed in patients without CKD at baseline, but not in those with CKD before the index operation. Anticoagulation over targeted INR values is associated with asteeper decline in eGFR and an increased frequency of CKD in patients with aMPV.

Verification of the qLabs international normalized ratio point-of-care device for monitoring of patients attending an anticoagulation clinic.

In the developing world, point-of-care (POC) testing for international normalized ratio (INR) plays an important role in the monitoring of patients on long-term warfarin therapy with limited access to healthcare ensuring safe and effective anticoagulation. A newly developed POC device for INR measurement by healthcare workers is the handheld qLabs POC device® (Micropoint Biotechnologies Incorporated, Guangdong, China). The qLabs POC device® was evaluated in 262 patients attending an anticoagulation clinic with regards to accuracy and precision of the INR results. The results were compared to the results obtained on the Stago STA R Max® coagulation analyzer (Stago Diagnostica, Paris, France) on a wide range of normal and abnormal results of clinical relevance. The mean laboratory INR (2.50±1.08) was significantly higher than the qLabs POC device® INR (2.38±1.07) (P<.0001). The correlation coefficient (r) was .88, the slope coefficient was 1.0 (CI, 0.8-1.2), and the intercept was -0.10 (CI, -0.50 to 0.30). The mean of the differences was -0.13% (CI, -0.19 to -0.06). Dosage concordance was 85.46% and clinical agreement was 92.37%. However, clinical agreement was 42.42% in the subgroup above the target range (>3.5). The imprecision was within acceptable limits (<5%) and the error message rate was 4.38%. In conclusion, the qLabs POC device® is accurate and precise with high levels of dosage concordance and clinical agreement for INR values within and below the target range.

International normalized ratio (INR) testing in Europe: between-laboratory comparability of test results obtained by Quick and Owren reagents.

Abstract Background: This study was designed to obtain an overview of the analytical quality of the prothrombin time, reported as international normalized ratio (INR) and to assess the variation of INR results between European laboratories, the difference between Quick-type and Owren-type methods and the effect of using local INR calibration or not. In addition, we assessed the variation in INR results obtained for a single donation in comparison with a pool of several plasmas. Methods: A set of four different lyophilized plasma samples were distributed via national EQA organizations to participating laboratories for INR measurement. Results: Between-laboratory variation was lower in the Owren group than in the Quick group (on average: 6.7% vs. 8.1%, respectively). Differences in the mean INR value between the Owren and Quick group were relatively small (&lt;0.20 INR). Between-laboratory variation was lower after local INR calibration (CV: 6.7% vs. 8.6%). For laboratories performing local calibration, the between-laboratory variation was quite similar for the Owren and Quick group (on average: 6.5% and 6.7%, respectively). Clinically significant differences in INR results (difference in INR&gt;0.5) were observed between different reagents. No systematic significant differences in the between-laboratory variation for a single-plasma sample and a pooled plasma sample were observed. Conclusions: The comparability for laboratories using local calibration of their thromboplastin reagent is better than for laboratories not performing local calibration. Implementing local calibration is strongly recommended for the measurement of INR.