Polymethyl Methacrylate-Based Smart Microfluidic Point-of-Care Testing of Prothrombin Time and International Normalized Ratio through Optical Detection.

The mechanical heart valve is a crucial solution for many patients. However, it cannot function on the state of blood as human tissue valves. Thus, people with mechanical valves are put under anticoagulant therapy. A good measurement of the state of blood and how long it takes blood to form clots is the prothrombin time (PT); moreover, it is an indicator of how well the anticoagulant therapy is, and of whether the response of the patient to the drug is as needed. For a more specific standardized measurement of coagulation time, an international normalized ratio (INR) is established. Clinical testing of INR and PT is relatively easy. However, it requires the patient to visit the clinic for evaluation purposes. Many techniques are therefore being developed to provide PT and INR self-testing devices. Unfortunately, those solutions are either inaccurate, complex, or expensive. The present work approaches the design of an anticoagulation self-monitoring device that is easy to use, accurate, and relatively inexpensive. Hence, a two-channel polymethyl methacrylate-based microfluidic point-of-care (POC) smart device has been developed. The Arduino based lab-on-a-chip device applies optical properties to a small amount of blood. The achieved accuracy is 96.7%.

Effect of an Elevated Preoperative International Normalized Ratio on Transfusion and Complications in Primary Total Hip Arthroplasty with the Enhanced Recovery after Surgery Protocol.

OBJECTIVE: To verify whether an elevated preoperative international normalized ratio (INR) increases transfusion and complications independently in primary total hip arthroplasty (THA) with the management of an enhanced recovery after surgery (EARS) protocol. METHODS: We retrospectively reviewed the database of adults who underwent primary THA between 2014 and 2018 by the same surgeon. A total of 552 patients were assigned into three groups by preoperative INR class: INR ≤ 0.9, 0.9 < INR < 1.0, and INR ≥ 1.0. We regarded transfusion within 90 days during the same hospitalization as the primary outcome. We also included perioperative blood loss, maximum Hb drop, postoperative anaemia requiring medicine, and length of hospital stay (LOS) during the same hospitalization in the study. Complications and reoperation at 90 days and mortality at 90 days and 12 months were also included in the study. Univariable analyses were utilized to compare baselines and outcomes among the three groups. Multivariate logistic regressions were used to adjust for differences at baseline among the groups. RESULTS: All patients had an INR < 1.5 preoperatively and were managed with the ERAS protocol. Among them, 93 (16.8%) patients had INR ≤ 0.9, 268 (48.6%) patients had 0.9 < INR < 1.0, and 191 (34.6%) patients had INR ≥ 1.0. In the univariable analyses, as the INR increased, the transfusion rates increased from 1.08% for INR ≤ 0.9, to 1.12% for 0.9 < INR < 1.0 and to 5.76% for INR ≥ 1.0 (P < 0.05). The overall complication rate increased from 10.8% for INR ≤ 0.9, to 16.4% for 0.9 < INR < 1.0, and to 22.5% for INR ≥ 1.0 (P < 0.05). The length of stay (LOS) in the INR ≥ 1.0 group was 5.7 ± 2.2 days, which was significantly longer than that in the INR ≤ 0.9 group (4.7 ± 1.6 days, P = 0.000) and 0.9 < INR < 1.0 group (5.1 ± 2.0 days, P = 0.007). No statistical significance was detected among the groups regarding blood loss, maximum Hb drop, or the incidence of postoperative anaemia that required medicine. There was no significant difference in reoperation or mortality among the groups. When controlling for demographic and comorbidity characteristics, there was no statistically significant difference in the odds of transfusion during the same hospitalization or overall complications at 90 days among the groups (P > 0.05). CONCLUSIONS: Elevated preoperative INR cannot increase transfusion or complication rates independently in primary THA with the management of the ERAS protocol. With the improvement in the ERAS protocol and the use of tranexamic acid (TXA), an INR < 1.5 is still a conventional safe threshold for THA surgery.

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression.

OBJECTIVES: D-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19. METHODS: A literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468). RESULTS: Thirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 â€‹% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 â€‹% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 â€‹% confidence interval, CI 0.42 to 0.77; p â€‹< â€‹0.001). There was extreme between-study heterogeneity (I2 â€‹= â€‹90.2 â€‹%; p â€‹< â€‹0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p â€‹= â€‹0.048) and D-dimer (p â€‹= â€‹0.001). CONCLUSIONS: Prolonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.

INR and not bilirubin levels predict postoperative morbidity in patients with malignant obstructive jaundice.

BACKGROUND: There are no established predictors for deciding between upfront surgery and PBD in pancreatic head malignancy. Once PBD is present, the ideal drainage-time remains elusive. The aim was, to identify predictors in jaundiced patients and ideal PBD-duration. METHODS: Analysis of 304 patients with pancreatic head malignancy (56% with PBD, n = 170) undergoing pancreaticoduodenectomy was performed. Postoperative morbidity and survival were analyzed. RESULTS: Postoperative complications increased after PBD (98.2% vs. 88.8%; p < 0.001). Patients with PBD received more postoperative antibiotics (42.4% vs. 21.6%; p < 0.001) and wound infections were increased (21.4% vs. 9.4%; p = 0.006). INR predicted postoperative morbidity (p = 0.026), whereas serum-bilirubin (p = 0.708), leucocytes (p = 0.158) and MELD-score (p = 0.444) had no impact. Complications were not different between long (>4 weeks) and short (<4 weeks) PBD-duration (p = 0.608). No life-threatening complications (CDIV + V) occurred after long drainage (0.0% vs. 8.9%; p = 0.028) and long-term survival was not compromised. CONCLUSIONS: INR is a suitable predictor for postoperative outcome, while serum-bilirubin levels had no predictive value. The INR can help deciding between PBD and upfront surgery. If PBD is inevitable, drainage duration of >4 weeks reduced major complications. CATEGORY: Clinical study.

The Association of International Normalized Ratio with Postoperative Complications in Revision Total Knee Arthroplasty.

The purpose of this study was to examine the relationship between elevated preoperative international normalized ratio (INR) and (1) mortality, (2) postoperative bleeding, and (3) other postoperative complications in a national cohort of patients who underwent revision total knee arthroplasty (rTKA). The American College of Surgeons National Surgical Quality Improvement Program was queried for rTKA procedures conducted between 2006 and 2017. Cohorts were based on INR ranges: <1, 1 < INR ≤ 1.25, 1.25 < INR ≤ 1.5, and >1.5. Univariate/multivariate statistics were calculated to analyze associations between INR value and designated covariates. These statistics were additionally applied to optimal cutoff values of INR calculated using a receiver operating characteristics curve. The final cohort consisted of 1,676 patients. Progressively higher INR values were associated with an increased risk of mortality within 30 days (p < 0.006), bleeding requiring transfusion (p < 0.001), sepsis (p < 0.001), return to the operating room (Odds Ratio [OR], p = 0.011), reintubation (p < 0.001), pneumonia (p < 0.001), failure to wean from mechanical ventilation ≤48 hours (p < 0.001), acute renal failure (p = 0.001), and hospital length of stay (LOS). Statistically significant associations were similarly seen when calculated optimal INR values were used. Optimal INR turn point was found to be associated with a significant increased risk of long LOS (optimal INR = 1.03, OR: 1.7, 95% confidence interval [CI]: 1.33-2.18; p < 0.001) and a significant decreased risk of bleeding requiring transfusion (INR = 1.005, OR: 0.732, 95% CI: 0.681-0.786; p < 0.001). High preoperative INR values were independently and significantly associated with an increased risk of multiple postoperative complications. Current guidelines for INR <1.5 should be reassessed for patients undergoing rTKA.

Coagulation Profile as a Significant Risk Factor for Short-Term Complications and Mortality after Anterior Cervical Discectomy and Fusion.

BACKGROUND: Cervical degenerative disc disease is the most common indication for anterior cervical discectomy and fusion. Given the possible complications, patients are stratified before anterior cervical discectomy and fusion by preoperative risk factors to optimize treatment. One preoperative factor is a patient's coagulation profile. METHODS: The American College of Surgeons-National Surgical Quality Improvement Database was used to identify patient preoperative coagulation profile and postoperative complications. By generating binary logistic regression models, each of the 4 abnormal coagulation categories (bleeding disorder, low platelet count, high partial thromboplastin time, and high international normalized ratio [INR]) were analyzed for their independent impact on increased risk for complications compared with the control cohort. RESULTS: A total of 61,977 patients were assessed. The most common abnormal coagulation was abnormal platelet count (n = 2149). The most common postoperative outcome was an extended length of hospital stay among patients with an abnormal coagulation profile relative to the control cohort. After multivariate analysis, patients with an abnormal INR (odds ratio, 2.2 [1.3-3.8]; P = 0.003) or abnormal platelet count (odds ratio, 1.5 [1.2-2.1]; P = 0.003) had a higher chance of having an extended length of hospital stay relative to patients having a normal coagulation profile. Having an abnormal INR was found to be associated with an increased risk for having "Any complication." CONCLUSIONS: Our results show significant differences in the incidence rates of a multitude of complications among the 5 groups based on univariate analysis. Patients with any abnormal coagulation disorder had increased rates of developing any complication or having an extended length of hospital stay.

Performance of the microINR Point-of-Care System: A Multicenter Clinical Trial.

INTRODUCTION: There are limited publications about the microINR point-of-care (POC) system (iLine Microsystems). The current microINR POC system was compared with the ACL TOP 500 laboratory analyzer (Instrumentation Laboratory) and with the CoaguChek XS POC system (Roche Diagnostics). METHODS: This study was performed at three United States medical centers. Sixty-eight nonanticoagulated normal donors and 245 warfarin anticoagulated patients were included. Testing was performed in duplicate using capillary blood samples for the POC systems and venous blood samples for the laboratory testing. Accuracy and imprecision were assessed. RESULTS: Comparing microINR to ACL revealed a correlation coefficient (r) of 0.973, a slope of 1.00 (95% confidence interval [CI], 0.97-1.03), and an intercept of 0.08 (95% CI, 0.04-0.15). When compared with the CoaguChek XS, r was 0.977 with a slope of 0.92 (95% CI, 0.89-0.94) and an intercept of 0.15 (95% CI, 0.08-0.19). Predicted bias values at international normalized ratio (INR) 2.0, 3.5, and 4.5 were ≤ 5% against both references. Agreement with ACL was 97, 95, and 100% for the INR ranges of < 2.0 ± 0.40, 2.0 to 4.5 ± 20%, and ≥ 4.5 ± 25%, respectively. Agreement for the combined INR ranges was 96% against ACL and > 96% against the CoaguChek XS. The coefficient of variation of the microINR was 5.03% for INR < 2.0 and 4.68% for the therapeutic INR range 2.0 to 3.5. CONCLUSION: The microINR results demonstrate adequate imprecision and accuracy to both ACL and CoaguChek XS. This indicates that monitoring INR by this microINR POC system is reliable and acceptable for the management of warfarin therapy.

The TRAAGIC score: early predictors of inpatient mortality in adult trauma patients

Background: Scoring systems are important in prognostication and decision-making in the management of trauma patients. However, they often include an extensive list of factors not easily recalled by clinicians on admission. Additionally, multivariable analyses examining predictors of mortality in these patients is lacking. This study aimed to develop and validate a mortality prediction score for adult trauma inpatients. The intention was to create a scoring tool that could be easily remembered and implemented by clinicians. Methods: This is a retrospective analysis of 5175 adult trauma patients treated at a level 1 trauma centre in Hamilton, Ontario, from 2002 to 2013. For derivation of the score, logistic regression was applied to data collected from 2002 to 2006 to identify potential predictors. Variables with p ≤ 0.10 identified from univariable analysis were entered in the multivariable logistic regression. Statistical significance was set at a value of 0.05. The prediction performance of the score was then assessed and validated on data for trauma patients treated from 2007 to 2013. The discrimination ability and calibration of the validation model were assessed. Frequencies, odds ratios with 95% confidence intervals (CIs) and C-statistics were reported. Results: The TRAAGIC prediction score (transfusion, age, airway, hyperglycemia, international normalized ratio, creatinine) showed a C-index of 0.85 (95% CI 0.83­0.87) in the derivation cohort. The TRAAGIC score had high discrimination and good calibration when applied to the validation cohort. Conclusion: The TRAAGIC score is an easily remembered and straightforward toolthat can reasonably predict inpatient mortality for adult trauma patients.

Contexte: Les systèmes de classification sont importants pour le pronostic et le processus décisionnel relatifs à la prise en charge des patients de traumatologie. Par contre, ces systèmes incluent souvent une longue liste de facteurs dont les cliniciens peuvent difficilement se rappeler quand un patient est admis. De plus, on déplore l'absence d'analyses multivariées sur les prédicteurs de mortalité chez ces patients. La présente étude visait à concevoir et valider un score de prédiction de la mortalité pour les polytraumatisés adultes hospitalisés. L'intention était de créer pour les médecins un outil de classification facile à retenir et simple à utiliser. Méthodes: Il s'agit d'une analyse rétrospective de 5175 polytraumatisés adultes traités dans un centre de traumatologie de niveau 1 de Hamilton, en Ontario, de 2002 à 2013. Le score est dérivé de l'analyse de régression logistique appliquée aux données recueillies de 2002 à 2006 pour dégager les prédicteurs potentiels. Les variables identifiées à partir d'analyses univariées dont p ≤ 0,10 ont été incluses dans l'analyse de régression logistique multivariée. La portée statistique a été fixée à 0,05. Le rendement prédictif du score a alors été évalué et validé pour les polytraumatisés traités de 2007 à 2013. On a évalué le pouvoir discriminant et l'étalonnage du modèle de validation, et on a fait état des fréquences, des rapports des cotes avec intervalles de confiance (IC) de 95 % et de la statistique C. Résultats: Le score de prédiction TRAAGIC (transfusion, âge, voies aériennes, hyperglycémie, ratio international normalisé, créatinine) a produit un indice de concordance de 0,85 (IC de 95 % 0,83­0,87) dans la cohorte de dérivation. Le score TRAAGIC s'est révélé doté d'un important pouvoir discriminant et d'un bon étalonnage lorsqu'on l'a appliqué à la cohorte de validation. Conclusion: Le score TRAAGIC est un outil facile à retenir et simple à utiliser qui permet de prédire raisonnablement le risque de mortalité chez les polytraumatisés adultes hospitalisés.

Tigecycline versus INR increase; more than expected?

Objectives: The aim of the study was to investigate the frequency of tigecycline-associated INR abnormality.Methods: Patients who were hospitalized between June and September 2016 and treated with tigecycline including therapy were extracted from hospital database and retrospectively reviewed. INR values at the beginning and end of treatment were compared.Results: A total of 79 patients who received tigecycline were identified by analyzing the hospital database. Nineteen patients were excluded from the study since INR was not measured at the beginning and/or end of treatment. In 55 of the 60 patients, INR levels were within normal limits (0.9-1.2) at the beginning of treatment while 19 of these 55 (34,5%) had prolonged INR after treatment. Prolongation was found to be mild (1.01-1.25 x ULN-upper limit of normal) in 12 of 19 patients, moderate (1.26-1.5 x ULN) in six and severe (1.51-3.0 x ULN) in one. In 10 of 19 patients, tigecycline was stopped, and the INR values normalized. There was no difference in INR abnormality rate between tigecycline monotherapy versus combination therapy receiving cases (19/27-33% vs. 10/33-30% p:1).Conclusion: These data show that INR prolongation may develop as common as 34.6% during tigecycline therapy. Regular INR follow-up may be beneficial in cases receiving tigecycline.

Revisiting the International Normalized Ratio Threshold for Bleeding Risk and Mortality in Primary Total Hip Arthroplasty: A National Surgical Quality Improvement Program Analysis of 17,567 Patients.

BACKGROUND: Efforts to identify preoperative risk factors for primary total hip arthroplasty have amplified with its increasing incidence. The international normalized ratio (INR) is 1 measure that may influence postoperative outcomes. This study of a national database assessed whether there exists an association between preoperative INR and postoperative bleeding and mortality among patients who underwent primary total hip arthroplasty. METHODS: We retrospectively analyzed 17,567 adult patients who underwent primary total hip arthroplasty in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) between 2005 and 2016. Patients were stratified by preoperative INR into 4 groups: INR <1.0, 1.0 to <1.25, 1.25 to <1.5, and ≥1.5. Bleeding necessitating transfusion was the primary outcome, and secondary outcomes included mortality, infection, and readmission. Multivariable logistic regressions controlled for baseline differences. RESULTS: Among the patients who underwent total hip arthroplasty, 20.5% had INR <1.0, 73.6% had INR 1.0 to <1.25, 4.2% had INR 1.25 to <1.5, and 1.8% had INR ≥1.5. Mortality increased incrementally from 0.3% for INR <1.0 to 4.9% for INR ≥1.5 (p < 0.001), and bleeding risk increased from 13.2% for INR <1.0 to 29.3% for INR ≥1.5 (p < 0.001). After adjustment, bleeding risk was increased for INR 1.25 to <1.5 (odds ratio [OR], 1.55 [95% confidence interval (CI), 1.26 to 1.92]) and INR ≥1.5 (OR, 1.55 [95% CI, 1.15 to 2.08]) compared with INR <1.0. The only group associated with increased mortality was INR ≥1.5 (OR, 2.69 [95% CI, 1.07 to 6.76]). The length of stay significantly increased with increasing INR, from 3.6 to 6.3 days (p < 0.001). CONCLUSIONS: This study found a significant, independent effect between increased preoperative INR and increased bleeding and mortality. Bleeding risk becomes evident at INR ≥1.25, and those patients with INR ≥1.5 are at significantly increased risk of mortality. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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.

Predictors of Warfarin Time in Therapeutic Range after Continuous-Flow Left Ventricular Assist Device.

INTRODUCTION: Patients with a continuous-flow left ventricular assist device (CF-LVAD) require anticoagulation with a vitamin K antagonist to prevent thromboembolic events. Fluctuations in the international normalized ratio are associated with both increased thrombotic and bleeding episodes. To date, risk factors for low time in therapeutic range (TTR) among ambulatory patients with a CF-LVAD have not been explored. METHODS: A retrospective single-center analysis of 121 patients implanted with a CF-LVAD was performed. International normalized ratios were systematically recorded from the initial postdischarge outpatient visit to 12 months of time on the device. Risk factors for low TTR were evaluated using a multivariable linear regression analysis. Each of the 21 independent variables was entered into a stepwise regression designed to minimize the Akaike information criteria. RESULTS: In the multivariable analysis, the model output revealed that every 1-year increase in age was associated with a 0.4% increase in TTR (p=0.008), and every 1 mile further from clinic was associated with a 0.08% increase in TTR (p=0.03). Female sex was associated with a 10.1% decrease in TTR (p=0.04), type 2 diabetes was associated with an 11.5% decrease in TTR (p=0.006), and prior warfarin use was associated with an 8.3% decrease in TTR (p=0.03). CONCLUSION: In CF-LVAD recipients receiving warfarin, increasing age and distance from clinic are independent predictors of higher TTR. Female sex, type 2 diabetes, and prior warfarin use are independent predictors of lower TTR.

Transjugular Liver Biopsy: Safe Even in Patients With Severe Coagulopathies and Multiple Biopsies.

OBJECTIVES: To investigate the safety profile and diagnostic efficacy of transjugular liver biopsy (TJLB), with a focus on patients with severe coagulopathies and with multiple biopsies. METHODS: Clinical, laboratory, and demographic information was collected on 1,321 TJLBs in 932 patients (mean age 43.5 ± 23.2 years) performed between January 2009 and May 2017 to determine the diagnostic success rate and incidence of both major and minor complications in the 3-day and 30-day period post-biopsies. These outcomes were also analyzed for severely coagulopathic patients and a subgroup of patients who underwent multiple biopsies. RESULTS: The overall success rate (diagnostic yield) of the TJLB procedure was 97.7% (1,291/1,321). Overall, the major and minor complication rates were 1.0% (13/1,321) and 9.5% (126/1,321), respectively. In patients with multiple biopsies, the overall complication rate was similar to the entire study cohort, which was 10.4% (57/550). Patients were also stratified according to the platelet counts of 0-50, 51-100, 101-200, 201-300 and >300 × 10 platelets/µL. The overall complication rates were 8.0% (10/124), 11.6% (36/310), 9.9% (54/547), 11.9% (28/235), and 14.3% (11/77), respectively, and these were not statistically significant from each other. Patients were also stratified by international normalized ratio into 0-1, 1.1-2, 2.1-3, and >3. The overall complication rates of these patients were 8.0% (19/237), 11.8% (113/954), 16.3% (7/43), and 0% (0/9), respectively, and were not statistically significant from each other. DISCUSSION: TJLB is a highly efficacious, well-tolerated and safe procedure. It can be safely performed multiple times in the same patient or in critically ill, severely coagulopathic patients with no significant increase in the rate of complication while maintaining an extremely favorable diagnostic yield.

Relationship Between Anticoagulant Medication Adherence and Satisfaction in Patients With Stroke.

AIM: The aim of this study was to investigate the accuracy of the self-reported measure of adherence and the relation between adherence to warfarin use, demographic and clinical variables, and the satisfaction with the treatment in patients affected by stroke. METHODS: This is a correlational, quantitative, and cross-sectional study, carried out in the outpatient clinics of a public university hospital from October 2017 to April 2018. Sociodemographic and clinical data were collected through interviews and hospital charts, as well as by applying the Measurement of Treatment Adherence (MTA) and the Duke Anticoagulation Satisfaction Scale, in their Brazilian versions. Results of the international normalized ratio (INR) were collected. Measurements of accuracy of the MTA scale were calculated in relation to the INR classification. RESULTS: Of 99 patients (55.6% male with a mean age of 58.6 years), 57.6% presented with therapeutic INR values and 75.8% of the patients were adherent to the oral anticoagulant therapy according to the MTA. The accuracy analysis of the measurement provided by the MTA scale in relation to the INR classification showed a sensitivity of 77.2% and a specificity of 26.2%. The patients' satisfaction with the treatment was high. The Duke Anticoagulation Satisfaction Scale had an average total score of 46.4, with the dimension impact in the field having the highest score (20.3). CONCLUSION: Stroke patients were adherent and satisfied with the oral anticoagulant therapy. The MTA had good sensitivity and poor specificity. Sociodemographic and clinical characteristics identified were not associated with adherence and satisfaction with treatment.

Massive transfusion in upper gastrointestinal bleeding: a new scoring system.

Background: Massive transfusion in patients with upper gastrointestinal bleeding (UGIB) was not investigated. We developed a new scoring system to predict massive transfusion and to enhance care and early resource mobilization. Methods: Massive transfusion was defined as transfusion with ≥10 units of red blood cells within the first 24 h. Data were extracted from a 10-year, six-hospital database. Logistic regression was applied to derive a risk score for massive transfusion using data from 2006 to 2010, in 24,736 patients (developmental cohort). The score was then validated using data from 2011 to 2015 in 27,449 patients (validation cohort). Area under the receiver operating characteristic (AUROC) curve was performed to assess prediction accuracy. Results: Five characteristics were independently associated (p < .001) with massive transfusion: presence of band-form cells among white blood cells (band form >0), international normalized ratio (INR) >1.5, pulse >100 beats per minute or systolic blood pressure <100 mmHg (shock), haemoglobin <8.0 g/dL and endoscopic therapy. The new scoring system successfully discriminated well between UGIB patients requiring massive transfusion and those who did not in both cohorts (AUROC: 0.831, 95%CI: 0.827-0.836; AUROC: 0.822, 95% CI: 0.817-0.826, respectively). Conclusions: The new scoring system predicts massive transfusion requirement in patients with UGIB well. Key messages Massive transfusion is a life-saving management in massive upper gastrointestinal bleeding. How to identify patients requiring massive transfusion in upper gastrointestinal bleeding is poorly documented. Approximately 3.9% of upper gastrointestinal bleeding patients require massive transfusion. A new scoring system is developed to identify patients requiring massive transfusion with high accuracy.

Differences in Warfarin Pharmacodynamics and Predictors of Response Among Three Racial Populations.

BACKGROUND: Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown. METHODS: Using population PK/PD analysis, we attempted to identify predictors of S-warfarin clearance [CL(S)] and half maximal effective concentration (EC50) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients. RESULTS: Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. 243 and 234 mL/h, p < 0.01). EC50 showed a greater racial difference than CL(S) [1.03, 1.70 and 2.76 µg/mL for Asian, White and African American patients, respectively, p < 0.01). Significant predictors of INR included demographic/clinical (age, body weight, creatinine clearance and sex) and genotypic (CYP2C9*3,*8 and VKORC1 -1639G>A) factors, as well as African American ethnicity. In all three racial groups, genetic predictors of INR appeared to have greater influence than demographic/clinical predictors. Both CL(S) and EC50 contributed to the over-anticoagulation response to warfarin. Patients having VKORC1 -1639 G>A and/or factors associated with reduced CYP2C9 activity were more likely to have an INR ≥ 4. CONCLUSIONS: Although there were contrasting racial differences in CL(S) and EC50 that impacted on the INR, the racial difference in EC50 was greater than that for CL(S), thus explaining the higher warfarin requirement for African American patients.

Time-driven activity-based cost analysis for outpatient anticoagulation therapy: direct costs in a primary care setting with optimal performance.

OBJECTIVES: To determine how overall cost of anticoagulation therapy for warfarin compares with that of Novel Oral Anticoagulants (NOACs). Also, to demonstrate a scientific, comprehensive, and an analytical approach to estimate direct costs involved in monitoring and management of anticoagulation therapy for outpatients in an academic primary care clinic setting, post-initiation of therapy. METHODS: A population-based cross-sectional study was conducted in conjunction with observations of patient care processes between August 2014 and January 2015. The study was conducted in an academic primary care outpatient setting at Mayo Clinic's warfarin anticoagulation clinic, Rochester, MN. The anticoagulation clinic serves patients 18 years of age or older in Warfarin therapy management, for any indication, after referral from the patient's primary care provider. The study included anticoagulation clinic enrollment data on a population of 5,526 patients. Time-Driven Activity-Based Costing (TDABC) technique was applied. Detailed process flow maps which showed process steps for all the anticoagulation program components and care continuum phases were created. Staff roles associated with each of the process steps were identified and displayed on the maps. Process times and costs were captured and analyzed. The main outcome was direct cost of monitoring and management of anticoagulation therapy, post-initiation of therapy. RESULTS: The cost of warfarin management for patients who display unstable International Normalized Ratio (INR) is more than three times those who display stable INR over time. (Comparator to distinguish stability: Frequency of point-of-care visits needed by patients.) For complex anticoagulation patients, total cost of medication and monitoring for warfarin anticoagulation therapy is similar to that for NOACs. CONCLUSION: Despite warfarin being significantly less expensive to purchase than NOACs, overall warfarin management incurs higher costs due to laboratory monitoring and provider time than NOACs. NOAC treatment, therefore, may not be more expensive than warfarin therapy management for complex anticoagulation patients.

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

BACKGROUND: 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. DESIGN: Prospective cohort study. SETTING: Regular medical care. PARTICIPANTS: Information on 2011 individuals receiving vitamin K antagonists was available for analysis from the prospective multicenter thrombEVAL study. MEASUREMENTS: 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. RESULTS: 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%. CONCLUSIONS: 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.

[Evaluation of the quality of long-term anticoagulation therapy with antivitamin-K in atrial fibrillation]. / Évaluation de la qualité de l'anticoagulation au long cours par antivitamine-K dans la fibrillation auriculaire.

AIM: To assess the quality of long-term anticoagulation therapy with antivitamin-K in patients with atrial fibrillation by measuring the TTR and to determine the factors associated with a good TTR. PATIENTS AND METHODS: This is an observational study conducted over a period of three years (from January 2013 until December 2015) in the outpatient clinic of cardiology of Farhat Hached hospital of Sousse, Tunisia. Pre-established individual plugs were used for data collection. The data analysis was performed using the SPSS Software, version 20. RESULTS: Overall, 200 patients were eligible. Half of the patients did not know the risks of AVK and 29.1% were unaware of their interest. The average TTR was 57.3±18.2%. Good control of anticoagulation was obtained in 24.5% of patients. Those with a≥70% were more autonomous, observant, of urban origin, living in Sousse and Kairouan, with good knowledge about AVK and having a small left atrium. The factors associated negatively with TTR were hypertension, diabetes, old AF, hematological diseases, high number of medications taken daily and the presence of mitral insufficiency, mitral valve replacement, a tricuspid insufficiency or a tricuspid plasty. CONCLUSION: The quality of AVK anticoagulation in AF patients is insufficient. Improving this indicator would reduce the morbidity and mortality associated with AVK treatment.