International Normalized Ratio Values Research Articles

Time in Therapeutic Range for Dialysis Patients on Warfarin: Determination and the Effect of Dietary Intervention

This study aimed to identify the time in therapeutic range (TTR) for dialysis patients on warfarin, and improve TTR with dietary review and intervention of interacting foods. We identified 151 patients undergoing hemodialysis in two units who were being treated with warfarin from January 1, 2010, through February 1, 2018, who were included in the overall TTR study. Of these, 15 patients were available to undergo the dietary intervention. International normalized ratio values were collected retrospectively for all eligible hemodialysis patients, and TTR was calculated for each period in which the patient was on hemodialysis. Patients who were available and agreed to the intervention underwent targeted dietician review of interacting foods, and their TTR post-treatment was calculated. The median (interquartile range [IQR]) TTR was 44 (IQR, 29 to 53) % among the 151 patients. Among the 15 patients who underwent the intervention, median (IQR) TTR was 52 (IQR, 32 to 56) pre-intervention and 51 (IQR, 38 to 69) post-intervention (P=0.53). TTR for dialysis patients is low in this overall cohort despite patients being seen at an integrated health care system. Focused improvement projects such as dietary review of interacting foods may help increase a patient's TTR.

Evaluation of dosing and safety outcomes of low-dose prophylactic warfarin in children after cardiothoracic surgery.

Prophylactic warfarin with an International Normalized Ratio (INR) goal of 1.5 to 2.0 is one antithrombotic therapy utilized in children after cardiothoracic surgery (CTS); published sources suggest a dose of 0.1 mg/kg per day to achieve this goal. However, few studies have evaluated dosing in this population. The purpose of this study was to evaluate dosing and safety outcomes in children receiving warfarin after CTS. A descriptive, retrospective review was conducted to evaluate warfarin dosing and INR outcomes in patients 18 years of age or younger who underwent CTS and received prophylactic warfarin with an INR goal of 1.5 to 2.0 from January 2014 through December 2018. The primary objective was to determine the median initial warfarin dose. Secondary objectives included identifying the percentage of documented INR values that were outside the therapeutic range, the percentage of patients with therapeutic INRs at discharge, and the 30-day readmission rate. Twenty-six patients were included in the review. The median initial warfarin dosage was 0.07 mg/kg/d (interquartile range [IQR], 0.05-0.10 mg/kg/d). Of the total of 177 INR values collected during the entire study period, 67 (37.9%) were therapeutic, 64 (36.2%) were subtherapeutic, and 46 (26.0%) were supratherapeutic. Eighteen patients (69.2%) had at least 1 supratherapeutic INR at any point during the study period, most frequently on days 2 through 4 of therapy. At discharge, 11 patients (42.3%) had therapeutic INRs. Four patients (15.4%) were readmitted within 30 days, with bleeding documented in 2 patients during their readmission. The majority of patients received an initial warfarin dose less than that specified in published recommendations but still had a supratherapeutic INR at least once during the study period. When initiating warfarin after CTS, a dosage of <0.1 mg/kg per day and frequent monitoring may be needed to achieve an INR goal of 1.5 to 2.0.

Thromboelastography as a tool for monitoring blood coagulation dysfunction after adequate fluid resuscitation can predict poor outcomes in patients with septic shock.

Coagulation abnormalities are universal in patients with septic shock and likely play a key role in multiple organ dysfunction syndrome. Early diagnosis and management of sepsis-induced coagulopathy can influence the outcome. Thromboelastography (TEG) can effectively distinguish hypercoagulability and hypocoagulability in patients with septic shock. TEG may be a useful tool to objectively evaluate the degree and risk of sepsis. A total of 76 adult patients with septic shock were enrolled and divided into four groups: patients with hypotension requiring vasopressor and serum lactate level >2 mmol/L (group A), patients with hypotension requiring vasopressor and serum lactate level ≤2 mmol/L (group B), patients with mean arterial pressure ≥65 mmHg and serum lactate level >2 mmol/L (group C), and patients with mean arterial pressure ≥65 mmHg and serum lactate level ≤2 mmol/L (group D) after adequate fluid resuscitation. TEG values were obtained at the emergency room and after 6 hours of adequate fluid resuscitation. Data on fibrinogen (FIB) levels, international normalized ratio (INR), activated partial thromboplastin time (aPTT), blood gas, platelet count, and D-dimers were also collected. The length of stay in the intensive care unit was 9.11 ± 5.36 days. Mortality rate was 6.58%. The values of reaction time, kinetics time, maximum amplitude, alpha angle, aPTT, INR, serum creatinine, FIB, and sepsis-related organ failure assessment (SOFA) score showed a significant differences. The results of the routine coagulation tests, blood gas volume, platelet count, procalcitonin level, D-dimer level, white blood cell count, creatinine level, disseminated intravascular coagulation score, SOFA score, and TEG values after adequate fluid resuscitation were significantly different between groups A and B, groups A and C, groups A and D, groups B and D, and groups C and D. TEG is helpful in predicting the severity of sepsis and outcome of patients.

How to manage catheter-related right atrial thrombosis: Our conservative approach.

Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut epidemiological data are available. Catheter-related right atrial thrombosis is often asymptomatic; however, it can lead to serious complications and death. We report seven catheter-related right atrial thrombosis events occurred in five hemodialysis patients; two recurrences following primary treatment are included in the report, all of them managed with a conservative approach without catheter removal. Systemic anticoagulation (vitamin K antagonists), having a well-defined target of International Normalized Ratio of 2.5-3.0, combined with urokinase as a locking solution at the end of each hemodialysis session were the therapeutic strategy used in all patients. After the first month, the anticoagulation target was reduced to an International Normalized Ratio value of 1.5-2.0 and urokinase to a weekly administration. After sixth months, when no thrombus was identified at transthoracic echocardiographic examinations, the treatment was stopped. No bleeding complications were reported. The combination therapy here described is safe, quick, and effective, achieving the goal of not removing catheters.

Quality of anticoagulant therapy and the incidence of in‐stent thrombosis after venous stenting

BackgroundIn patients with a venous outflow obstruction following iliofemoral deep vein thrombosis stenting of the venous tract to prevent or alleviate postthrombotic syndrome is applied with increasing frequency. The impact of the quality of anticoagulant therapy with vitamin K antagonists (VKAs) on the development of in‐stent thrombosis is currently unknown. ObjectivesTo determine the association between the quality of postinterventional VKA treatment and the occurrence of in‐stent thrombosis. MethodsSeventy‐nine patients with iliofemoral and/or caval venous stent placement for obstruction of the venous outflow were included in this study. All patients received postinterventional VKA. The quality of VKA anticoagulant therapy was expressed as the time within therapeutic range (TTR) calculated using the linear interpolation method and as the proportion of International Normalized Ratio (INR) values < 2.0. In‐stent thrombosis was assessed by the use of duplex ultrasound. Survival analysis (Kaplan‐Meier curves, Cox regression) was used to analyze the data. ResultsIn‐stent thrombosis developed in 16 patients (20.3%). The total population had a mean TTR of 64.0% (±19.0) and a mean proportion of INR values < 2.0 of 11.6% (±12.0). Overall, a TTR < 49.9% was associated with an increased risk of in‐stent thrombosis. The multivariable adjusted analysis showed a hazard ratio (HR) of 0.96 (95% confidence interval [CI], 0.92‐0.99; P = .02) per 1% increase in TTR. The proportion of INR values < 2.0 had no significant association with the occurrence of in‐stent thrombosis: HR 0.98 (95% CI, 0.91‐1.06; P = .66). ConclusionsWe conclude that the quality of anticoagulant treatment reflected in the TTR following a venous stenting procedure is an important independent determinant for the risk of in‐stent thrombosis. The role of anticoagulant treatment for the prevention of in‐stent thrombosis following stenting procedures therefore merits further research.

COVID‐19 associated coagulopathy and thromboembolic disease: Commentary on an interim expert guidance

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the causative pathogen of a new infectious disease, COVID-19, that first occurred in late December 2019 in the city of Wuhan in Hubei Province, China. It has since spread globally, resulting in a WHO declared pandemic, with as yet (17/4/20) more than two million confirmed cases and about 150.000 confirmed deaths. As for every new disease, clinicians, hospitals and governments struggle to find optimal clinical and public health measures to contain its spread and burden. For this, information from scientific research is crucial and fortunately we see a rapidly accumulating output of studies.

Plasma Warfarin Level and International Normalized Ratio do not Correlate with Bleeding Events in Indonesian Patients of Minangkabau Ethnicity with Atrial Fibrillation

BACKGROUND: Warfarin is the mainstay of anticoagulant therapy to prevent thromboembolism in atrial fibrillation (AF). It has a narrow therapeutic window, rendering monitoring prothrombin time necessary using the international normalized ratio (INR). However, INR value is not always correlated with the clinical risk of bleeding.&#x0D; AIM: We aimed to monitor plasma warfarin concentration and to analyze its correlation with bleeding events in Indonesian patients of Minangkabau ethnicity with AF.&#x0D; METHODS: We consecutively recruited outpatients with AF from January to November 2017 at a tertiary hospital in West Sumatera, Indonesia. At the time of the study, patients had received at least 5 weeks of warfarin. Their characteristics were obtained from medical records, and INR data were collected. Warfarin plasma concentration was analyzed using high-performance liquid chromatography.&#x0D; RESULTS: There were a total of 45 patients (25 males and 20 females; mean age 54.6 years). The number of patients with INR value lower than, within, and higher than target value (2.0–3.0) was 25, 12, and 8, respectively. Half of the patients (n = 23; 51.1%) had subtherapeutic plasma warfarin levels and nearly half (n = 20; 44.4%) of the patients had therapeutic plasma warfarin levels. INR value was not significantly correlated with plasma warfarin level (r = 0.273; p = 0.07). Bleeding events occurred in 14 patients. INR value was not significantly different (p = 0.12), while the plasma warfarin level was marginally significantly different (p = 0.05) between those with bleeding and no bleeding events.&#x0D; CONCLUSION: Neither warfarin plasma concentration nor INR was correlated with bleeding events in Indonesian patients of Minangkabau ethnicity with AF.

Risk of Cardiovascular Events and Mortality Among Elderly Patients With Reduced GFR Receiving Direct Oral Anticoagulants

Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs). Population-based retrospective cohort study. All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to2016. DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m2). The primary outcome was a compositeof a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization. High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression. 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m2. No interaction was detected for the outcome of hemorrhage. Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power. DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

Comparing therapy outcomes of patients before and after enrolling in an anticoagulation self‐testing program

AbstractPurposePatients managed by the Froedtert &amp; the Medical College of Wisconsin (F&amp;MCW) Anticoagulation Clinics (ACC) have three monitoring options: face‐to‐face management, telephone management, or self‐testing management with limited clinician interaction only when International Normalized Ratios (INRs) are out of range or when clinically appropriate. To investigate if F&amp;MCW ACC's current method of less frequent interaction for self‐testing is safe and effective, the purpose of this study was to determine if patients taking warfarin who were previously managed either face‐to‐face or via telephone call in the F&amp;MCW ACC can be as effectively managed while self‐testing at home.MethodsThis pre‐post study analyzed data from face‐to‐face or telephone call anticoagulation management 6 months before and after each patient's self‐testing teach‐visit date. The primary outcome was the patients' time in therapeutic range (TTR) for INR values before and after enrolling in the self‐testing program. Secondary outcomes were the number of major bleeding and thromboembolic events and the number of INRs greater than 5.0 before and after transitioning to INR self‐testing. Patients served as their own control group for all outcomes of this study.ResultsThe mean (standard deviation [SD]) TTR for subjects 6 months before and after transitioning to self‐testing was 69.9% (20.9) and 73.2% (18.0), respectively, demonstrating a statistically significant increase in TTR of 3.3% (25.4) with self‐testing (P = .047). Thirty‐six critical values occurred in the 6 months before self‐testing and 24 occurred in the 6 months after transitioning to self‐testing (P = .23). Additionally, four major bleeding and thromboembolic events occurred in four different patients in the 6 months after transitioning to self‐testing (P = .13).ConclusionsF&amp;MCW ACC's model for self‐testing management of every 2‐week self‐tests and limited clinician interaction demonstrates statistically significant improvements in TTR after patients transitioned to self‐testing. There was no statistically significant increase in adverse events following this transition.

Top-down and bottom-up approaches for the estimation of measurement uncertainty in coagulation assays

The assessment of measurement uncertainty (MU) in clinical laboratories is essential to the reliable interpretation of results in clinical laboratories. However, despite the introduction of various methods for the expression of uncertainty in measurement, the MUs of coagulation tests have not been extensively studied. The aim of this study was to quantify the MU of various coagulation assays according to international guidelines and to report an expected confidence in the quality of coagulation assays. We selected activated partial thromboplastin time, international normalized ratio (INR), protein C/S, antithrombin, fibrinogen, and Factor V/VIII/X to quantify the MUs of two coagulation testing systems: ACL TOP 750 CTS (Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). We used international standards and interlaboratory comparison results in accordance with international guidelines in a top-down approach to the assessment of MU. For INR, MU was estimated in a bottom-up approach using reference thromboplastin and certified plasmas. Top-down approaches resulted in MUs between 3.3% and 21.3% for each measurand. In the bottom-up approach, MUs of INR values ranged from 10.9% to 26.4% and showed an upward trend as INR increased. In this study, we were successful in quantifying MU of coagulation assays using practical methods. Our results demonstrated that top-down and bottom-up approaches were adequate for coagulation assays. However, some assays showed significant biases against international standards; therefore, standardization would be necessary to ensure more reliable patient results.

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.

A Novel LC-MS/MS Assay for Quantification of Des-carboxy Prothrombin and Characterization of Warfarin-Induced Changes.

Warfarin is a narrow therapeutic index anticoagulant drug and its use is associated with infrequent but significant adverse bleeding events. The international normalized ratio (INR) is the most commonly used biomarker to monitor and titrate warfarin therapy. However, INR is derived from a functional assay, which determines clotting efficiency at the time of measurement and is susceptible to technical variability. Protein induced by vitamin K antagonist‐II (PIVKA‐II) has been suggested as a biomarker of long‐term vitamin K status, providing mechanistic insights about variation in the functional assay. However, the currently available antibody‐based PIVKA‐II assay does not inform on the position and number of des‐carboxylation sites in prothrombin. The assay presented in this paper provides simultaneous quantification of carboxy and des‐carboxy prothrombin that are essential for monitoring early changes in INR and, thus, serves as the superior tool for managing warfarin therapy. Additionally, this assay permits the quantification of total prothrombin level, which is affected by warfarin treatment. Prothrombin recovery from plasma was 95% and the liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) assay was linear (r 2 = 0.98) with a dynamic range of 1–100 µg/mL. The assay interday precision was within 20%. A des‐carboxy peptide of prothrombin (GNLER) was negatively correlated with active prothrombin (Pearson r = 0.99, P < 0.0001), whereas its association was positively linked with INR values (Pearson r = 0.75, P < 0.015). This novel LC‐MS/MS assay for active and inactive prothrombin quantification can be applied to titrate anticoagulant therapy and to monitor the impact of diseases, such as hepatocellular carcinoma on clotting physiology.

The Effect of Nurse Home-Support Program on Self-Management of Patients Receiving Oral Anticoagulation (Warfarin) Therapy.

AimWarfarin, which is widely used for preventing thromboembolic events, can cause major and minor side effects. The aim of this trial is to evaluate the effect of nurse home-support program on self-management of patients receiving warfarin therapy.MethodA randomized, controlled trial was conducted using 36 selected and eligible patients who had 12-month home-visit follow-ups. The bleeding risk score, potential and preventable warfarin-related complications, patients’ self-management behaviors, and anticoagulation satisfaction were examined. Data analyses were performed using parametric and nonparametric tests, split-plot analysis of variance, multiple regression analysis, and Bland and Altman plots test.ResultsThe bleeding risk score was an effective variable for assessing patient satisfaction (p<0.05). The self-management group demonstrated decreased bleeding risk at the end of the trial. The Duke Anticoagulation Satisfaction Scale mean score represents a statistically significant improvement in the self-management group (p<0.05). Patients’ self-management behaviors improved significantly in the self-management group compared to the control group (p<0.05). The number of international normalized ratio values within the target range was significantly higher in the self-management group (174/432) than in the control group (82/432). The self-management group showed significant reductions in both thromboembolic events.ConclusionThis trial demonstrated evidence that use of nursing home care is effective in developing self-management behaviors, improving patient satisfaction, and preventing complications in patients receiving warfarin therapy. This model could be easily adopted and implemented by home care services and health organizations.

Sofosbuvir/ledipasvir in treatment of HCV infected Egyptian patients with decompensated liver cirrhosis Child Pugh class (B)

Abstract Background The main goal of anti-HCV therapy in patients with decompensated (Child-Pugh B) cirrhosis not on a transplant waiting list is to achieve improvement in liver function and survival. Several studies have demonstrated acceptably high SVR rates, equivalent in Child-Pugh B patients, in individuals with decompensated cirrhosis, together with an effect of therapeutic viral clearance on liver function, with significant improvements in bilirubin, albumin and international normalized ratio values and, as a result, in MELD and Child-Pugh scores in one-third to half of patients. Similar results were reported in real-world studies. Patients with Child-Pugh B cirrhosis benefited more from viral clearance in terms of adverse event-free survival at 15 months than those with Child-Pugh C cirrhosis. Aim of the Work Assessment of the safety &amp; efficacy of sofosbuvir/ ledipasvir in infected naïve and experienced HCV Egyptian patients with decompensated liver disease. Patients and Method This study was conducted on 100 patients with HCV related decompensated liver disease who presented to the hepatology outpatient clinic in El Agouza Police hospital and were evaluated according to the inclusion and exclusion criteria. Conclusion Ledipasvir/sofosbuvir is effective and safe in the treatment of HCV decompensated patients Child Pugh B. MELD and Child scores significantly improved with HCV treatment in decompensated patients Recommendations Longer follow up with assessment of the need for liver transplantation or HCC development is important. Larger number of patients is required.

4:03 PM Abstract No. 362 To screen or not to screen: can we accurately limit the preoperative testing of coagulation status in patients undergoing placement of tunneled central venous catheter to only those that need it?

To determine if the preoperative screening and evaluation of coagulation status in patients undergoing placement of a tunneled central venous catheter, as reflected by the platelet count and the calculated International Normalized Ratio (INR), can be accurately limited to specific patients based upon known risk factors and relevant past medical history in accordance with the recommendations set forth in the updated SIR Guidelines for the Periprocedural Management of Bleeding Risk. We conducted a retrospective analysis of tunneled central venous catheter placements performed by interventional radiology in both the ambulatory and inpatient setting at a single institution over a 12-month period between August 1st, 2018 and July 31st, 2019. The preoperative platelet and INR values were compiled from the electronic medical record. Any encountered platelet or INR abnormalities (platelet count < 20 x 109/L, INR > 3.0) were then cross-referenced to the relevant patient medical history to determine the etiology of the coagulation deficit. A total of 578 tunneled central venous catheters (142 ports, 103 permacaths, 16 Hickman catheters, 317 Powerline catheters) were placed during the study period. Coagulation testing was performed within 3 days or 30 days of the procedure (inpatient vs. ambulatory setting, respectively) in accordance with current departmental protocol. Of the 578 tunneled catheter placements, 1 patient (0.17%) demonstrated an INR value above the threshold limit and 12 patients (2.1%) possessed a platelet count below the recommended transfusion threshold. The laboratory abnormalities in all cases were easily explained: the elevated INR was secondary to Coumadin therapy for atrial fibrillation and the thrombocytopenia was related to a hematologic malignancy in every instance. The presence of a coagulation deficit in a patient undergoing a tunneled central venous catheter placement is rare and, when encountered, explained by a review of the relevant past medical history. These findings support the updated Periprocedural Guidelines for low bleeding risk procedures recommending preoperative laboratory screening only in patients with relevant risk factors.

Understanding risk factors and predictors for stroke subtypes in the ENDURANCE trials

Stroke is a devastating morbidity associated with left ventricular assist device (LVAD) support. We report a comprehensive analysis of stroke subtypes in the ENDURANCE destination therapy (DT) and ENDURANCE Supplemental (DT2) trials. Patients in the combined HeartWare LVAD (HVAD) cohorts of the DT and DT2 trials were included. Neurologic events included ischemic stroke (ischemic cerebrovascular accident [ICVA]), hemorrhagic stroke (hemorrhagic cerebrovascular accident [HCVA]), and transient ischemic attack (TIA). Peri-operative strokes were defined as occurring within 2 weeks of the implant. A total of 604 patients received an HVAD in the DT (n = 296) and DT2 (n = 308) trials. Over 2 years, 178 (29.5%) had at least 1 cerebrovascular accident (CVA). Forty-four (7.3%) had HCVAs, 116 (19.2%) had ICVAs, and 44 (7.3%) had TIAs. Thirty (5.0%) had peri-operative stroke. In multivariable analysis, sub-therapeutic international normalized ratio (INR) values were independently associated with peri-operative stroke. Supra- and/or sub-therapeutic INR values, peripheral vascular disease, and presence of left ventricular thrombus were independently associated with ICVA. No aspirin and supra- and/or sub-therapeutic INR values were independently associated with TIA. No aspirin, supra- and/or sub-therapeutic INR values, and prior stroke and/or TIA were associated with HCVA. In further analysis, mean arterial pressure (MAP) was higher in the ICVA (86.8mmHg, p = 0.0024) and TIA (88.8mmHg, p<0.0001) groups, but not in HCVA, than in the No-CVA group (81.4mmHg). Time in therapeutic range for INR was 65.3% for the No-CVA group, 62.9% (p = 0.59) for HCVA, 65.1% (p = 0.97) for ICVA, and 63.2% (p = 0.62) for TIA. Supra- and sub-therapeutic INR values at the time of CVA were associated with all stroke subtypes >14 days post-implant. MAP was higher among those with ICVA and TIA but not with HCVA compared to without CVA. Our study demonstrates the challenges of anti-thrombotic therapy and blood pressure management in LVAD population.

Laparoscopic cholecystectomy in patients with liver cirrhosis: 8 years experience in a tertiary center. A retrospective cohort study.

BackgroundWith improved laparoscopic techniques, experience, and availability of newer tools and instruments like ultrasonic shears; laparoscopic cholecystectomy (LC) became a feasible option in cirrhotic patients, the aim of this study was to analyze the outcome of LC in cirrhotic patients. Methods: We retrospectively analyzed 213 cirrhotic patients underwent LC, in the period from 2011 to 2019; the overall male/female ratio was 114/99. Results: The most frequent Child-Turcotte-Pugh (CTP) score was A, The most frequent cause of cirrhosis was hepatitis C virus (HCV), while biliary colic was the most frequent presentation. The harmonic device was used in 39.9% of patients, with a significant correlation between it and lower operative bleeding, lower blood and plasma transfusion rates, higher operative adhesions rates, lower conversion to open surgery and 30-day complication rates, shorter operative time and post-operative hospital stays where operative adhesions and times were independently correlated. The 30-day morbidity and mortality were 22.1% and 2.3% respectively while overall survival was 91.5%, higher CTP, and model for end-stage liver disease (MELD) scores, higher mean international normalization ratio (INR) value, lower mean platelet count, higher operative bleeding, higher blood, and plasma transfusion rates, longer mean operative time and postoperative hospital stays were significantly correlated with all conversion to open surgery, 30-day morbidities and mortalities. Conclusion: LC can be safely performed in cirrhotic patients. However, higher CTP and MELD scores, operative bleeding, more blood and plasma transfusion units, longer operative time, lower platelet count, and higher INR values are predictors of poor outcome that can be improved by proper patient selection and meticulous peri-operative care and by using Harmonic scalpel shears.

Comparison of prothrombin time and international normalized ratio values using point-of-care system with a standardized laboratory method in patients on long-term oral anticoagulation – A prospective study

Background: In our country, methods of prothrombin time (PT) and international normalized ratio (INR) testing have not been standardized across various centers. Often, we find disparity in INR values from different laboratories, posing a challenge to make an appropriate clinical decision. Objective: The objective of the study was to compare and correlate the PT/INR values using a point-of-care (POC) system with standardized laboratory (SL) testing and to evaluate the efficiency of the POC system in monitoring patients. Methods: We have prospectively compared PT/INR values between a commercially available POC, CoaguChek XS System, Roche, and SL testing in 205 patients and 353 samples from July 2017 to April 2018. Results: The overall strong correlation between POC PT/INR values and simultaneous standard laboratory values was noted. The overall coefficient of correlation among the two groups was 0.919 (P = 0.001) for INR values. In INR range of 2–3.5, the values correlated well with a coefficient of correlation, 0.756 (P = 0.001). In INR range 4. Conclusions: In this comparison study, statistical analysis yielded a good correlation between POC PT/INR values and SL values in therapeutic and subtherapeutic range. POC testing is a good alternative to SL testing. If widely available, POC testing may enable patient self-testing and self-monitoring. In our experience, POC testing had added benefits in emergency settings. However, clinicians and laboratory professionals should be aware of the occasional disagreement between POC INR and standard laboratory INR values.

Quality of anticoagulation with warfarin in rural Chhattisgarh, India

Background & objectives:In most of rural India, warfarin is the only oral anticoagulant available. Among patients taking warfarin, there is a strong association between poor control of the international normalized ratio (INR) and adverse events. This study was aimed to quantify INR control in a secondary healthcare system in rural Chhattisgarh, India.Methods:The INR data were retrospectively obtained from all patients taking warfarin during 2014-2016 at a secondary healthcare system in rural Chhattisgarh, India. Patients attending the clinic had their INR checked at the hospital laboratory and their warfarin dose adjusted by a physician on the same day. The time in therapeutic range (TTR) was calculated for patients who had at least two INR visits.Results:The 249 patients had 2839 INR visits. Their median age was 46 yr, and the median body mass index was 17.7 kg/m2. They lived a median distance of 78 km (2-3 h of travel) from the hospital. The median INR was 1.7 for a target INR of 2.0-3.0 (n=221) and 2.1 for a target of 2.5-3.5 (n=28). The median TTR was 13.0 per cent, and INR was subtherapeutic 66.0 per cent of the time. Distance from the hospital was not correlated with TTR.Interpretation & conclusions:INR values were subtherapeutic two-thirds of the time, and TTR values were poor regardless of distance from the health centre. Future studies should be done to identify interventions to improve INR control.

Pharmacokinetics of Dexmedetomidine in Infants and Children After Orthotopic Liver Transplantation.

Dexmedetomidine (DEX) is a sedative and analgesic medication that is frequently used postoperatively in children after liver transplantation. Hepatic dysfunction, including alterations in drug clearance, is common immediately after liver transplantation. However, the pharmacokinetics (PK) of DEX in this population is unknown. The objective of this study was to determine the PK profile of DEX in children after liver transplantation. This was a single-center, open-label PK study of DEX administered as an intravenous loading dose of 0.5 μg/kg followed by a continuous infusion of 0.5 μg/kg/h. Twenty subjects, 1 month to 18 years of age, who were admitted to the pediatric intensive care unit after liver transplantation were enrolled. Whole blood was collected and analyzed for DEX concentration using a dried blood spot method. Nonlinear mixed-effects modeling was used to characterize the population PK of DEX. DEX PK was best described by a 2-compartment model with first-order elimination. A typical child after liver transplantation with an international normalized ratio (INR) of 1.8 was found to have a whole blood DEX clearance of 52 L/h (95% confidence interval [CI], 31-73 L/h). In addition, intercompartmental clearance was 246 L/h (95% CI, 139-391 L/h), central volume of distribution was 186 L/70 kg (95% CI, 140-301 L/70 kg), and peripheral volume of distribution was 203 L (95% CI, 123-338 L). Interindividual variability ranged from 11% to 111% for all parameters. Clearance was not found to be associated with weight but was found to be inversely proportional to INR. An increase in INR to 3.2 resulted in a 50% decrease in DEX clearance. Weight was linearly correlated with central volume of distribution. All other covariates, including age, ischemic time, total bilirubin, and alanine aminotransferase, were not found to be significant predictors of DEX disposition. Children who received DEX after liver transplantation have large variability in clearance, which was not found to be associated with weight but is influenced by underlying liver function, as reflected by INR. In this population, titration of DEX dosing to clinical effect may be important because weight-based dosing is poorly associated with blood concentrations. More attention to quality of DEX sedation may be warranted when INR values are changing.