International Normalized Ratio Group Research Articles

The Effect of Serum Magnesium Level on Stable Anticoagulation in Patients Using Warfarin for Various Cardiac Indications.

Warfarin is a vitamin K antagonist agent that inhibits clotting factors used for long-term anticoagulation. Time in therapeutic range (TTR) in patients using warfarin is one of the primary treatment effectiveness requirements. We aim to investigate the relationship between serum magnesium levels, the international normalized ratio (INR) values, and TTR values in people using warfarin for various indications. Our study is a single-center, cross-sectional, and retrospective study that included 169 patients between 18 and 70 who used warfarin for various indications. Demographic data, biochemical analysis, and coagulation parameters, including TTR calculation, were evaluated for all patients. Those with a TTR value below 60 were defined as labile INR, and those with 60 and above as stable INR group and compared. The mean INR value was higher in the labile INR group than the stable INR group (3.7 ± 2.9, 3.2 ± 0.3, respectively; p = 0.030). The Mg values are significantly lower in the labile INR group than the stable group (1.8 ± 0.2mg/dL, 2.0 ± 0.1mg/dL, respectively; p < 0.001). In binary multivariate logistic regression analysis, magnesium value was the most influential INR stabilization factor (p < 0.001). As a result of our study, it was concluded that magnesium levels are an influential factor in stabilizing INR. We can state that we have contributed to the literature and can be a reference for future studies.

Clinical significance for combined coagulation indexes in epithelial ovarian cancer prognosis

BackgroundIncreasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC).MethodsA retrospective study was conducted on patients who underwent optimal tumor debulking followed by platinum-based chemotherapy at our institution. The predictive value of coagulation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for recurrence-free survival (RFS) and overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis.ResultsWe involved 482 EOC patients and followed up for 64 (range, 36–87) months. According to ROC curves, D-dimer and International normalized ratio (INR) had superior predictive value than other coagulation indexes, with area under curve (AUC) of 0.758 and 0.742. Patients were then stratified into three combined D-dimer and INR (DD-INR) groups based on the cut-off value of 0.97 mg/L and 0.86, respectively. Through regression analysis, we demonstrated that age (HR 1.273; 95%CI 1.048–2.047; p = 0.045), pathological grade (HR 1.419; 95% CI 1.102–2.491; p = 0.032), clinical stage (HR 2.038; 95%CI 1.284–3.768; p = 0.008), CA-125 (HR 1.426; 95%CI 1.103–1.894; p = 0.038) and DD-INR (HR 2.412; 95%CI 1.683–3.241; p = 0.009) were independent prognostic factors. Survival analysis showed that patients with higher DD-INR experienced poor survival (p = 0.0013 for RFS and p = 0.0068 for OS). Further subgroup analysis revealed that evaluated DD-INR was significantly associated with poor survival among patients with advanced stage (p = 0.0028 for RFS and p = 0.0180 for OS).ConclusionOur findings suggested that coagulation indexes, especially the combined DD-INR were promising biomarkers for prognosis stratification in EOC patients, especially those with advanced clinical stages.

Association of Preoperative Coagulability With Incidence and Extent of Portal Vein Tumor Thrombus and Survival Outcomes in Hepatocellular Carcinoma After Hepatectomy: A Large-Scale, Multicenter Study.

BackgroundOccurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR).MethodsPatients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method.ResultsThis study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P<0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P<0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P<0.001).ConclusionPreoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.

Precannulation International Normalized Ratio is Independently Associated With Mortality in Veno-Arterial Extracorporeal Membrane Oxygenation

To explore whether precannulation international normalized ratio (INR) is associated with in-hospital mortality in venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. A retrospective, observational cohort study. A quaternary care academic medical center. Patients with cardiogenic shock on VA-ECMO for >24 hours. None, observational study. A total of 188 patients who were on VA-ECMO were included over three years. Patients were stratified into three groups based on their pre-ECMO INR: INR <1.5, INR 1.5 to 1.8, and INR >1.8. For all patients, demographics, comorbidities, and ECMO details were recorded. The study's primary outcome was in-hospital mortality and secondary outcomes included major bleeding, minor bleeding, allogeneic transfusion, ischemic stroke, intracranial hemorrhage, acute renal failure, acute liver failure, gastrointestinal bleeding, intensive care unit and hospital lengths of stay. A multivariate logistic regression was used to determine whether precannulation INR was associated independently with in-hospital mortality. In-hospital mortality differed significantly by INR group (51.6% INR >1.8 v 42.3% INR 1.5-1.8 v 24.3% INR <1.5; p=0.004). In a multivariate logistic regression model, precannulation INR >1.8 was associated independently with an increased odds of mortality (odds ratio, 2.48; 95% confidence interval, 1.05-6.04) after controlling for sex, Survival after VA- ECMO score, and ECMO indication. An INR within 1.5 to 1.8 did not confer an increased mortality risk. An INR >1.8 before VA-ECMO cannulation is associated independently with in-hospital mortality. Precannulation INR should be considered by clinicians so that ECMO resources can be better allocated and risks of organ failure and intracranial hemorrhage can be better understood.

Incidence of Major Bleeding Associated with International Normalized Ratio Greater Than 4.0 in a Cohort of Mechanical Circulatory Support Device Patients

To study the frequency by which a significantly elevated international normalized ratio (INR) may be associated with a major bleeding event in mechanical circulatory support device (MCS) patients. A retrospective review of mechanical circulatory support device recipients was performed for the years 9/2013-5/2018. The incidence of significant bleeding was determined using the MOMENTUM 3 major adverse event bleeding definition. The incidence of bleeding within 30 days of an INR>4.0 was assessed. Sixty-Four MCS patients (36 Heartware, 18 Heartmate II, 7 Heartmate III, 3 total artificial heart) were reviewed for INR data over the study period. Only ten patients never had any INR values above 4.0. A total of 217 INR measurements were found to be greater than 4.0. There was a total of 56 major bleeding events in 33 patients during the study period. Eleven patients experienced 17 major bleeding events associated with INR>4.0, however 39 bleeds did not register an INR>4.0. The incidence of bleeding and high INR as measured by positive predictive value was 8.3% with a sensitivity of 0.306. The negative predictive value for freedom from bleeding with INR<4.0 was 99.5% with a specificity of 0.968. The average time to bleed after a measured INR>4.0 was 10.3 +/- 10.0 days. Both the bleeding and the non-bleeding groups had an average total number of INR values>4.0 for the study period of 3.9 +/- 3.5. There were 9 gastrointestinal bleeds (GIB), and 6 non GIBs that required transfusion, as well as 2 intracranial hemorrhages (ICH) in the elevated INR group. No bleeds within a month of an INR>4.0 group were fatal, whereas two ICHs in the INR<4.0 group were fatal. A single elevated INR>4.0 did not correlate strongly with an incidence of major bleeding in the subsequent 30 days. The amount of time to bleeding events after an elevated INR is also quite variable making the forecasting of potential bleeding difficult. Further study is warranted to improve our understanding of the link between the frequency, amount of time, and individual significance of supratherapeutic INR and bleeding complications.

Quality of Oral Anticoagulation with Vitamin K Antagonists in ‘Real-World’ Patients: Lessons from a Six Years Audit Study

Introduction: Among patients receiving vitamin K antagonists (VKA) therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. This requires regular monitoring and appropriate dose adjustment. It has been reported that anticoagulation clinics should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. Previously (in a study between September 2006 and June 2012), we have reported that patients with longer INR recall interval (4-8 weeks) showed no decrease of monitoring quality and that it would be safe to increase time between measurements. Aim: Since actual recommendations for improving TTR include shortening INR recall interval (Lip et al. 2018) we aimed to evaluate the quality of anticoagulation monitoring after having increased time between measurements beyond the 4-8 weeks recall interval. Methodology: We retrospectively analyzed 37931 appointments of 6 consecutive years (July 2012 to July 2018) corresponding to 1587 patients that are regularly followed up at an outpatient Anticoagulation Clinic of a central hospital under anticoagulation for at least 8 weeks, using TTR determined by Rosendaal method. Patients were divided according to target INR in three groups: Group 1 with target INR 2-3, including 1430 patients corresponding to 30743 appointments with mean age 69±15 years (mean±SD), majority (46.4%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 125 patients corresponding to 5439 appointments with mean age 67±12 years, majority (85.6%) with mechanical heart valves; Group 3 with target INR 3-4, including 32 patients corresponding to 1749 appointments with mean age 62±14 years, majority (62.5%) with antiphospholipid syndrome. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests and correlations were performed. Results: The 1587 patient population, 50.5% male, mean age of 68±17 years and 90.1% in Group 1, showed a mortality of 18%. A point-biserial correlation was run to determine the relationship between mortality and gender, age, INR group and diagnostic. Mortality was correlated with diagnosis (57.2% with AF) (rpb = -.071, n = 1587, p = .004), male gender (60%) (rpb = -.089, n = 1587, p &lt;.001) and age (75±12) (rpb = .175, n= 1587, p&lt;.001) but not with INR group (rpb = -.017, n = 1587, p = .499). Indeed, between groups mortality was not different [Χ2(2)=.492; p=.782; φ=.018] nor mean age [F(2, 1584)=2.588; p=.078; η2=.003], but gender distribution was unequal [Χ2(2)= 10.815; p=.004; φ=.083] with male predominating in Group 1 (51.9%) and female in Group 2 (60.8%) and 3 (65.6%). Patients in Group 1, corresponding to 90.1% of the total population, had TTR of 72%, patients in Group 2 had TTR of 69% and patients in Group 3 had TTR of 60%. Comparatively to the previous study (2006-2012), we noticed a significant decrease in patient population / appointments size (2087/ 61988) (p &lt;.001) with a decrease of TTR in Group 1 (1927 patients) (83%) and Group 2 (120 patients) (74%) but a TTR increase in Group 3 (40 patients) (54%) (p &lt;.001). Conclusions and Discussion: More than 90% of the population under VKA treatment showed effective TTR which may infer safety in increasing INR recall interval. The TTR decrease with a smaller population may be explained by the introduction of direct oral anticoagulants in patients with less comorbidities. The increase of TTR in patients with higher INR target suggests a better management of patients under VKA therapy that is actually the only choice for challenging patients. Disclosures No relevant conflicts of interest to declare.

Vitamin K antagonist has a higher impact than heparin in preventing circuit clotting in chronic haemodialysis patients.

BackgroundIn dialysis sessions, some data suggest that decreasing or even avoiding additional anticoagulation by heparin is possible among patients already treated with oral anticoagulation. However, the required dose of heparin may actually depend on the pre-dialysis international normalized ratio (INR), which varies from one session to another. The aim of our study was to determine the respective role of INR and heparin dosing in the risk of circuit clotting during chronic haemodialysis.Methods From early 2012 to July 2016, we analysed the totality of dialysis sessions performed at Brest University Hospital among haemodialysis patients treated by vitamin K antagonists (VKA). We established a prediction of circuit clotting on the basis of a simplified score obtained by combining INR and heparin dosing.ResultsIn total, 7184 dialysis sessions among chronic haemodialysis patients under VKA were identified, including 233 with clotting events. The mean INR without clotting events was 2.5 versus 1.8 with clotting events (P < 0.001). Frequencies of circuit clotting were different according to INR group (INR <2.0, INR 2.0–3.0, INR >3.0; P < 0.0001). The protective role of VKA was higher than heparin, as shown by discriminant factor analysis (P < 0.0001). Conclusion. Our study established a predictive model of thrombosis risk of dialysis circuits in patients treated by VKA for a given heparin dose and a given INR. This model shows a marginal contribution of heparin to protect against the risk of thrombosis compared with VKA. Moreover, heparin would not appear to be necessary for patients with an INR >2.2.

International Normalized Ratio (INR) is Comparable to MELD in Predicting Mortality after Cholecystectomy

Guidelines suggest targeting a preoperative international normalized ratio (INR) < 1.5. We examined and compared the predictive value of INR relative to the Model for End-Stage Liver Disease (MELD). We reviewed the American College of Surgeons NSQIP from 2005 to 2016 for adult patients undergoing open or laparoscopic cholecystectomy. Patients with a preoperative INR were stratified into groups: ≤1, >1 to ≤1.5, >1.5 to ≤2, and >2. Thirty day postoperative mortality was the primary outcome. Multivariable logistic regressions controlled for baseline differences. Of 58,177 cholecystectomy patients, 15.2 per cent had INR ≤ 1, 80.4 per cent had INR > 1 to ≤1.5, 3.7 per cent had INR > 1.5 to ≤2, and 0.7 per cent had INR > 2. Patients with INR > 2 were older and more likely to have diabetes and hypertension (P < 0.001). Multivariable regression demonstrated a stepwise increase in mortality for INR > 1 to ≤1.5 (odds ratio (OR) = 1.50 [1.10-2.05]), INR > 1.5 to ≤2 (OR = 2.96 [1.97-4.45]), and INR > 2 (OR = 3.21 [1.64-6.31]) relative to INR ≤ 1. C-statistic for INR (0.910) and MELD (0.906) models indicated a similar value in predicting mortality. INR groups also faced an incremental, increased risk of bleeding. Although unable to track preoperative correction of INR, this analysis identifies that INR remains an excellent predictor of postoperative mortality and bleeding after both open and laparoscopic cholecystectomies and is comparable to MELD.

Revisiting the International Normalized Ratio (INR) Threshold for Complications in Primary Total Knee Arthroplasty: An Analysis of 21,239 Cases.

Consensus guidelines recommend use of the international normalized ratio (INR) to predict the risk of perioperative bleeding in orthopaedic surgery. However, current recommendations for targeting an INR of <1.5 are based on studies across all surgical disciplines. This study examined the impact of the INR on perioperative bleeding, mortality, postoperative infections, length of hospital stay (LOS), and readmissions following primary total knee arthroplasty (TKA). We retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database for adult patients who underwent primary TKA from 2010 to 2016. Patients for whom an INR had been recorded within 1 day before the surgery were stratified and analyzed for perioperative bleeding, mortality within 30 days, deep wound and superficial infections, LOS, and readmissions. Multivariable regressions were utilized to adjust for differences in demographics and comorbidities among INR groups. Of 21,239 patients, 57.2% had an INR of ≤1.0; 38.1% had an INR of >1.0 to 1.25, 3.9% had an INR of >1.25 to 1.5, and 0.8% had an INR of >1.5. After adjustment, a progressively increased bleeding risk was found with an INR of >1.0 to 1.25 (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.07 to 1.31, p = 0.001), an INR of >1.25 to 1.5 (OR = 1.29, 95% CI = 1.02 to 1.63, p = 0.033), and an INR of >1.5 (OR = 2.02, 95% CI = 1.29 to 3.14, p = 0.002) relative to an INR of ≤1.0. Patients with an INR of >1.5 were at increased risk for infection (OR = 5.34, 95% CI = 2.45 to 11.68, p < 0.001), but only patients with an INR of >1.25 to 1.5 were at increased risk for mortality (OR = 3.37, 95% CI = 1.31 to 8.63, p = 0.011) relative to those with an INR of ≤1.0. Overall and TKA-related readmission rates and LOS were significantly increased for patients with an INR of >1.25 to 1.5 or an INR of >1.5. An INR of >1.25 to 1.5 was associated with increased bleeding, infection, and mortality rates following TKA, and an INR of >1.5 was associated with increased bleeding and infection rates. Current INR target recommendations in consensus guidelines should be reconsidered. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Prognostic Value of International Normalized Ratio in Ischemic Stroke Patients without Atrial Fibrillation or Anticoagulation Therapy.

Aim: The impact of international normalized ratio (INR) on prognosis after acute ischemic stroke without anticoagulation therapy is unclear. Herein, the association between baseline INR and stroke outcomes in patients without anticoagulation therapy was investigated.Methods: A total of 14,782 ischemic stroke patients from the China National Stroke Registry II were included in this analysis. The period of follow-up was 1 year after stroke onset. Multivariate logistic regression models were used to estimate the relationship between INR and stroke outcomes including all-cause death, recurrent stroke, composite end point, and poor functional outcome.Results: Of 14,782 patients with stroke, all-cause death occurred in 1080 (7.3%), recurrence stroke in 538 (3.9%), combined end point in 1319 (8.9%), and poor functional outcome in 3001 (20.3%). Compared with the medium INR group (0.9–1.1), the odds ratios with confidence intervals of 95% for the high INR group (> 1.1) were 1.58 (1.32–1.98) for all-cause death, 1.40 (1.10–1.79) for stroke recurrence, 1.52 (1.29–1.79) for combined end point, and 1.21 (1.06–1.39) for poor functional outcome. No association between low INR (< 0.9) and any stroke outcomes was found compared with the medium group.Conclusions: Increased admission INR was associated with adverse stroke outcomes among acute ischemic stroke patients without atrial fibrillation or anticoagulation therapy.

EVALUATION OF WARFARIN ORAL USED BY INTERNATIONAL NORMALIZED RATIO VALUE AND DETERMINATION FREQUENCY TO CARDIOVASCULAR PATIENT AT HAJI ADAM MALIK GENERAL HOSPITAL, MEDAN, INDONESIA

Objective: The objective of this research was to evaluate of warfarin oral used by value and determination frequency of international normalized ratio (INR).Methods: The data of cardiovascular patients were collected from medical records in Haji Adam Malik General Hospital, Medan, North Sumatera, Indonesia, in 2016. This study evaluated the data by retrospective study design. The sample study was selected by Slovin method from the population of medical record of cardiovascular patients who received warfarin therapy. The sample of population was divided based on how many times the INR was measured. The groups are no measurement, once a year, unregularly schedule, thrice a year, and every month. The data were analyzed by analysis of variant to evaluated association of INR values and groups of patients.Result: The total sample in this study was 90 patients based on Slovin formula. The percentage of patient who never gets INR checked was 18.89%, once a year was 32.2%, unregularly was 34.44%, thrice a year was 8.89%, and every month was 5.56%. The value of INR in groups was 0.00 ± 0.00 in never checked group, once in year was 1.18 ± 0.44, unregularly was 1.79 ± 1.00, once time in 3 months was 2.04 ± 0.73, and every month was 2.42 ± 0.91. The groups of patients with never evaluation of INR value were significantly different with the other groups (p≤0.05).Conclusion: The results obtained in this study indicated the majority patients group in case of warfarin oral used and evaluation of bleeding status were once checked in year and unregularly determination of INR value. The best condition, in this case, was the determination of INR value in every month caused the bleeding or coagulation status of patient can be evaluated.

Effect of Ramadan Fasting on the International Normalized Ratio in Patients with Mechanical Prosthetic Heart Valves

Background: Maintaining a therapeutic range of International Normalized Ratio (INR) in patients with mechanical prosthetic heart valves is of paramount importance. The effect of religious Fasting and altered lifestyle pattern during the Holy month of Ramadan on the INR stability has not been previously studied in the Saudi population. Objectives: We aimed to evaluate the effect of Ramadan fasting on the INR stability in patients using warfarin anticoagulation for mechanical prosthetic heart valves. Design: Data were extracted retrospectively from a specialized anticoagulation clinic electronic database and were anlysed in a case-control manner, where Ramadan INR of each study subject was compared to his/her own pre-Ramadan INR level. Setting: Prosthetic Valve Anticoagulation Clinic at King Abdul-Aziz Cardiac Center, Riyadh. Materials and methods: Using Point-Of-Care (POC) testing, the first INR level during Ramadan as compared to the average baseline INR readings over the last 3 months before Ramadan. The study was conducted between July 29th and August 20th, 2015, which corresponds to the month of Ramadan, 1436 Hejra Calendar. Several exclusion criteria were applied to minimize the effects of potential confounding factors. Main Outcome measures: Paired t-test was used to detect any statistically significant difference in the INR level between Ramadan and pre-Ramadan readings, in the overall study cohort and among pre-specified study subgroups. Results: One-hundred and fourteen (114) consecutive patients fulfilled the inclusion criteria. Mean age was 48.4±13.6 years and males constituted 58% of cases. Low target (INR: 2.0-3.0) and high target (INR: 2.5-3.5) therapeutic ranges represented 35% and 65% respectively. Mean INR level was 2.81 at baseline and 2.75 during Ramadan with no statistically significant difference between them (P=NS). Achieving the desired target INR level before Ramadan was feasible in 62.5% and 64.8% of the low and high INR target groups respectively. However, maintaining the desired INR level during Ramadan was feasible in 67.5% and 51.3% of the low and high target INR groups respectively (P= 0.07). Duration of anticoagulation, warfarin dose, and adherence scale did not contribute significantly to the primary outcome. Conclusion: Ramadan fasting and its associated lifestyle changes in the Saudi community may aggravate the INR fluctuations in warfarin-treated patients. During Ramadan, warfarin-treated patients are more prone to develop supra-therapeutic INR and therefore they deserve careful attention and closer INR monitoring.

On-X Valve: The Next Generation Aortic Valve.

The On-X valve is a newer generation mechanical bileaflet valve. Its key features include the use of pure pyrolytic carbon (devoid of silicon), a length-to-diameter ratio similar to a native valve, an inlet flared orifice, a leaflet opening up to 90 degrees, a shorter leaflet closing angle, a 2-point leaflet contact, and an actuated pivot. These features have translated into increased strength, improved valve hemodynamics, reduced hemolysis, and thrombogenicity. The 2014 American Heart Association/American College of Cardiology guidelines for the management of patients with valvular heart disease recommend an international normalized ratio (INR) of 2.5 (range, 2-3) in patients with a mechanical valve at the aortic position. However, based on the results of the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT), the Food and Drug Administration approved this valve in April 2015 in the aortic position with a lower INR goal of 1.5-2.0. This reduction in INR goals led to a statistically significant reduction in the combined endpoint of clots, bleeding events, and stroke rates with 9/patient-years for the lower INR group compared with 12/patient-years in the standard INR group. This review compares the currently available literature on the On-X valve with that of other contemporary valves.

Real-World Impact of Setting a Narrow International Normalized Ratio Target Range in the Management of Older Adult Patients on Warfarin

Elderly patients intrinsically have higher bleeding risks, deterring clinicians from prescribing them oral anticoagulants. Setting a narrow international normalized ratio (INR) target range might potentially mitigate some of these risks. This study sought to compare the outcomes of elderly patients who were assigned to either a narrow INR target range or the conventional INR target range in a real-world environment. This was a retrospective cohort study with the primary and secondary outcomes being the mean percentage time above INR 3.0 and the mean percentage time below INR 2.0 and the incidents of bleeding and thromboembolism associated with oral anticoagulant therapy, respectively. Patients and health care workers managing them had no prior knowledge of this study. Data of 150 patients with a narrow INR target range (2.0-2.5) and 164 patients with a conventional INR target range (2.0-3.0) were collected and analyzed. The narrow INR group had significantly higher underlying risks of bleeding than the conventional INR group. Patients in the narrow INR group had a significantly lower percentage time above INR 3.0 but no significant difference in the percentage time below INR 2.0. Adjusted incidence rate ratio (IRR) for bleeding events was significantly lower for the narrow INR group, while the adjusted IRR for thromboembolic events between both groups was similar. Patients assigned to a narrow INR target range in real-world practice spent a significantly lower amount of time below an INR of 3.0 compared to conventional INR target range with lower incidents of bleeding complications and no increase in subtherapeutic INRs.

Comorbidities against quality control of VKA therapy in non-valvular atrial fibrillation: a French national cross-sectional study.

BackgroundGiven the prevalence of non-valvular atrial fibrillation in the geriatric population, thromboembolic prevention by means of vitamin K antagonists (VKA) is one of the most frequent daily concerns of practitioners. The effectiveness and safety of treatment with VKA correlates directly with maximizing the time in therapeutic range, with an International Normalized Ratio (INR) of 2.0-3.0. The older population concentrates many of factors known to influence INR rate, particularly concomitant medications and concurrent medical conditions, also defined as comorbidities.ObjectiveDetermine whether a high burden on comorbidities, defined by a Charlson Comorbidity Index (CCI) of 3 or greater, is associated a lower quality of INR control.Study-DesignCross-sectional study.SettingsFrench geriatric care units nationwide.Participants2164 patients aged 80 and over and treated with vitamin K antagonists.MeasurementsComorbidities were assessed using the Charlson Comorbidity Index (CCI). The recorded data included age, sex, falls, kidney failure, hemorrhagic event, VKA treatment duration, and the number and type of concomitant medications. Quality of INR control, defined as time in therapeutic range (TTR), was assessed using the Rosendaal method.Results487 patients were identified the low-quality control of INR group. On multivariate logistic regression analysis, low-quality control of INR was independently associated with a CCI ≥3 (OR = 1.487; 95% CI [1.15; 1.91]). The other variables associated with low-quality control of INR were: hemorrhagic event (OR = 3.151; 95% CI [1.64; 6.07]), hospitalization (OR = 1.614, 95% CI [1.21; 2.14]).ConclusionAn elevated CCI score (≥3) was associated with low-quality control of INR in elderly patients treated with VKA. Further research is needed to corroborate this finding.

Warfarin associated intracerebral hemorrhage in Hong Kong Chinese

Objectives: Warfarin-associated intracerebral hemorrhage (WICH) is a serious neurological condition associated with significant mortality and morbidity. We aimed to study the clinical features and factors that predict clinical outcome of Chinese patients with WICH.Methods: Medical records of patients with spontaneous intracerebral hemorrhage (ICH) admitted to our hospital between July 2001 and June 2010 were reviewed and those with WICH were studied in detail retrospectively.Results: Fifty-one patients with WICH were studied. The mean age was 74·3 ± 10·5 years and 52·9% of the patients were female. The mean international normalized ratio (INR) on presentation was 2·9 ± 1·0. The median ICH volume was 23·3 (10·4–59·3) ml. The mortality rate at 3–6 months for WICH was 62·0%. Multivariate logistic analysis revealed that an initial ICH volume of > 20 ml (OR 34·4, P = 0·037) and presence of intraventricular hemorrhage (OR 22·9, P = 0·046) were independently associated with poor outcome. Supratherapeutic INR (INR > 3·0) on admission (P = 0·724) and complete correction of INR within 24 hours after admission (P = 0·486) were not independent predictors of poor outcome. The median ICH volumes did not differ between INR groups (18·2 (9·4–61·1) ml for INR ≤ 3 vs 27·3 (13·7–58·5) ml for INR > 3, P = 0·718). Neurological deterioration (ND) was documented in 19 (63·3%) of the 30 patients included in a smaller sub-cohort, and was associated with poor neurological outcome (OR 20·7, P = 0·027). Warfarin was resumed in 7 of the 20 survivors. There were two episodes of recurrent WICH and one episode of ischemic stroke during a mean follow-up duration of 5·4 years. In survivors who were not resumed on warfarin, there were two episodes of recurrent ICH and 12 episodes of ischemic vascular events (nine ischemic strokes) during a mean follow-up duration of 2·6 years.Conclusion: Warfarin-associated intracerebral hemorrhage is a very serious complication of warfarin therapy with high mortality and morbidity. Initial ICH volume, presence of intraventricular hemorrhage, and ND are independent predictors of clinical outcome.

INR reduction after prothrombin complex concentrate (Co-fact©) administration: comparison of INR outcomes in different patient categories at the emergency department

BackgroundCo-fact©, prothrombin complex concentrate, is used for restoring the international normalized ratio (INR) in patients on vitamin K antagonists (VKA) presenting with acute bleeding. In this prospective cohort study, we evaluated whether adequate INR values were reached in ED patients using the Sanquin (Federation of Dutch Thrombosis Services) treatment protocol.MethodsWe evaluated this protocol for two target INR groups: group 1, target INR ≤ 1.5 (for life-threatening bleeding/immediate intervention); group 2, target INR 1.6-2.1 (in cases of a minor urgent surgery or serious overdosing of anticoagulant). We specifically wanted to identify both under- and over-treated patients. Reversing VKA anticoagulation therapy to unnecessarily low INR values may involve thrombotic risks. Apart from this risk, the patient is also administered an excess amount of the drug. This means unnecessary costs and may present problems with restoring an anticoagulated state at a later time.ResultsIn our cohort, the Sanquin dosing protocol was followed for 45/60 patients. It appeared that out of the 41 patients in group 1 (target INR ≤ 1.5), 35 (85%) achieved the goal INR. This occurred more often than for the 19 patients in group 2 (target INR 1.6–2.1), where only 6 (32%) achieved the goal INR. Using the protocol resulted in a positive trend toward better INR reversal in group 1. In group 2, no relation between using the protocol and achieving the desired INR value was detected. Physicians ignoring the proposed dose of Co-fact© prescribed significantly less Co-fact© (even when correcting for patient weight). It appeared that patients in group 1 had a significantly lower baseline INR than patients in group 2. Group 2 patients, on the other hand, had a baseline INR > 7.5 in 53% of the cases.ConclusionIn our cohort, for most patients in INR group 2 treated with Co-fact©, the achieved INR value was outside the desired range of 1.6-2.1. The supra-therapeutic range of baseline INR in group 2 may have contributed to the different kind of bleeding witnessed in this patient group. Our results support the idea that treatment of patients on vitamin K antagonists with Co-fact© could benefit from a slightly different approach, taking into account the INR value to which the patient needs to be reversed.

Preoperative Low Dose Recombinant Activated Factor VII Effect during Liver Transplantation

Background: End stage liver disease patients are prone to coagulopathy and frequently require blood transfusion during transplantation. Methods: Prospective study (2008-2011) to investigate the effect of prophylactic intravenous administration of low dose recombinant activated factor VII (rFVIIa) (20 μ/kg) 30 min prior to surgery and repeated one hour later on Standard Coagulation Tests (SCTs), Rotational Thromboelastomery (ROTEM) and Blood Transfusion (BT) requirements during Living Donor Liver Transplantation (LDLT). SCT include Prothrombin Time (PT), International Normalized Ratio (INR) of prothrombin time, Activated Partial Thromboplastin Time (aPPT), fibrinogen and platelets blood levels. ROTEM include EXTEM and INTEM representing coagulation extrinsic and intrinsic pathways respectively, and FIBTEM for fibrinogen activity. Blood transfusion was guided by ROTEM parameters. Control group(C), n=25 and rFVII group, n=25 Results: Both groups preoperative MELD scores, ROTEM and SCTs were comparable (P>0.05). After initial dose to end of dissection, a reduction in INR and aPTTin rFVII group versus control were observed, associated with a reduction in clotting time (CT) and increased alpha angle in ROTEM (P 0.05). BT correlated positively with dissection time (r=0.7, p<0.01), but weakly with preoperative HB (r=-0.3, p<0.05). Conclusion: Low dose rFVII monitored by ROTEM improved coagulation and reduced BT requirements with no evidence of thromboembolic events. Dissection time was another important contributing factor.

Clinical Utility and Accuracy of Coaguchek® XS, a Reliable Alternative to Laboratory International Normalized Ratio Monitoring in Korean Patients With Atrial Fibrillation

Background and Objectives: To evaluate the accuracy and the clinical utility of the Coaguchek ® XS, a portable point-of-care coagulometer, compared to standard laboratory methods in Korean patients. Subjects and Methods: We included 107 patients with atrial fibrillation on long-term oral warfarin therapy. The prothrombin time as expressed by the international normalized ratio (INR) was measured by the portable Coaguchek ® XS system as well as standard laboratory methods. Agreement between the two methods was defined as a difference of less than 0.3 between the INR values. Results: The INR determined by the portable Coaguchek ® XS had excellent correlation with the values obtained by standard methods (r=0.984, p 3.0). There was a 91.6% agreement between the two methods. Only nine cases (8.4%) had a difference of more than 0.3; this was mainly noted in the high INR group. Conclusion: The portable self-testing of the INR by the Coaguchek ® XS might be a reliable

Frequency and effect of optimal anticoagulation before onset of ischaemic stroke in patients with known atrial fibrillation

The aims of the study were (i) to examine which antithrombotic therapy patients with known atrial fibrillation use at the point of time when they suffer an ischaemic stroke, (ii) to evaluate the effects of optimal antithrombotic treatment on outcome and severity of the stroke. Patients with known atrial fibrillation before onset of acute ischaemic stroke, and age >60 years were included. Antithrombotic therapy on admission was classified into four groups: no antithrombotic therapy, aspirin, sub-optimal anticoagulation (warfarin and international normalized ratio, INR<2.0) and optimal anticoagulation (warfarin and INR>or=2.0). modified Rankin Scale (mRS) 5 or 6 at day 7 poststroke. (i) death or discharge to a nursing home, (ii) death, (iii) stroke severity on admission assessed by Scandinavian Stroke Scale. A total of 394 patients were included. On admission 109 (28%) patients used no antithrombotic therapy, 169 (43%) aspirin, 52 (13%) warfarin and had an INR<2.0, and 64 (16%) used warfarin and had an INR>or=2.0. The proportion of patients with an mRS 5 or 6 and the corresponding odds ratios were: in the warfarin group with INR<2.0, 16 (31%), OR 3.1 (CI: 1.2-8.0), (P=0.019), in the group with no antithrombotic therapy 29 (27%), 2.5 (1.1-5.9), (P=0.034), and in the aspirin group 41(24%), 2.2 (1.0-5.1) (P=0.054), compared with the warfarin group with INR>or=2.0, where eight (13%) patients had a poor outcome. A significantly higher proportion of patients died or were discharged to a nursing home in the warfarin group with an INR<2.0 (P=0.014), in the aspirin group (P=0.018) and in the no-treatment group (P=0.035), compared with the warfarin group with an INR>or=2.0. No significant differences were found regarding death alone and stroke severity on admission. Few patients with known atrial fibrillation who suffer an ischaemic stroke receive optimal antithrombotic therapy prior to the onset of stroke. Optimal anticoagulation does not only reduce the risk of ischaemic stroke, but also appears to reduce death and severe dependency as well as the need for nursing home care, if an ischaemic stroke occurs.