International Normalized Ratio Values Research Articles

Antithrombotic Treatment Prior to Intracerebral Hemorrhage: Analysis in the National Acute Stroke Israeli Registry

Background and PurposeIntracerebral hemorrhage (ICH) is the most disastrous stroke subtype. Prognosis is considered worse with prior antithrombotic treatment. Our aim was to evaluate the association of prior antithrombotic treatment on the radiological and clinical outcome after ICH in a subgroup of patients included in a national registry. MethodsBased on the National Acute Stroke Israeli (NASIS) registry during 2004, 2007, 2010, and 2013 (2-month periods), characteristics, volumetric parameters, and prognosis of a subgroup of patients with ICH were analyzed. ResultsAmong the 634 patients with ICH in the NASIS registry, 310 (49%) were not treated previously with antithrombotic medications, 232 (37%) were treated with an antiplatelet agent, and 92 (14.5%) patients were on oral anticoagulant therapy, of them 30 patients (33%) with an international normalised ratio (INR) value below 2, 33 (36%) patients with an INR value of 2-3, and 29 patients (31%) with an INR value above 3 upon admission. Patients with deep hemorrhage on prior anticoagulants treatment had the highest probability for poor outcome at hospital discharge. Patients with low bleeding volume (0-30 cm3), were likely to have admission National Institute of Health Stroke Scale < 10 (62%), while those with higher volumes (30-59 cm3 and > 60 cm3), had only 16.7% and 14.3% chance, respectively. We did not observe a significant difference between prior antithrombotic treatment and functional outcome at discharge, yet prior anticoagulant treatment was associated with higher long-term mortality rates. ConclusionsOur findings, based on a national registry, support the high mortality and poor outcome of anticoagulant related ICH.

International Normalized Ratio and Mortality Risk in Acute Heart Failure and Nonvalvular Atrial Fibrillation Patients Receiving Vitamin K Antagonists.

Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up. In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality. During a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years' follow-up: -0.50; 95%CI, -0.77 to -0.23 years; P < .001; and -0.40; 95%CI, -0.70 to -0.11 years; P = .007, respectively, compared with INR 2-3. In acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk.

Point-of-care coagulation testing for reducing in-hospital delay in thrombolysis

Background: The confirmation of prothrombin time international normalized ratio by a central laboratory often delays intravenous thrombolysis in patients with acute ischemic stroke. Objectives: We investigated the feasibility, reliability, and usefulness of point-of-care determination of prothrombin time international normalized ratio for stroke thrombolysis. Methods: Among 312 patients with ischemic stroke, 202 who arrived at the emergency room within 4.5 h of stroke onset were enrolled in the study. Patients with lost orders for point-of-care testing for the prothrombin time international normalized ratio or central laboratory testing for the prothrombin time international normalized ratio (n = 47) were excluded. We compared international normalized ratio values and the time interval from arrival to the report of test results (door-to-international normalized ratio time) between point-of-care testing for the prothrombin time international normalized ratio and central laboratory testing for the prothrombin time international normalized ratio. In patients who underwent thrombolysis, we compared the time interval from arrival to thrombolysis (door-to-needle time) between the current study population and historic cohort at our center. Results: In the 155 patients included in the study, the median door-to-international normalized ratio time was 9.0 min (interquartile range, 5.0–12.0 min) for point-of-care testing for the prothrombin time international normalized ratio and 46.0 min (interquartile range, 38.0–55.0 min) for central laboratory testing for the prothrombin time international normalized ratio (p &lt; 0.001). The intraclass correlation coefficient between point-of-care testing for the prothrombin time international normalized ratio and central laboratory testing for the prothrombin time international normalized ratio was 0.975 (95% confidence interval: 0.966–0.982). Forty-nine of the 155 patients underwent intravenous thrombolysis. The door-to-needle time was significantly decreased after implementation of point-of-care testing for the prothrombin time international normalized ratio (median, 23.0 min; interquartile range, 16.0–29.8 vs median, 46.0 min; interquartile range, 33.5–50.5 min). Conclusion: Utilization of point-of-care testing for the prothrombin time international normalized ratio was feasible in the management of patients with acute ischemic stroke. Point-of-care testing for the prothrombin time international normalized ratio was quick and reliable and had a pivotal role in expediting thrombolysis.

Elevated International Normalized Ratio Is Associated With Ruptured Aneurysms.

Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.

Effects of cigarette smoking on coagulation screening tests and platelet counts in a Sudanese male adults population.

Objectives:To study the effects of heavy cigarette smoking on coagulation (CGG) screening tests and platelet counts (PLTs) in a Sudanese male adults population.Methods:A case control study was conducted at both Kosti and Gabalein towns, Sudan, during October 2016 to May 2017. A 100 adult cigarette smokers were selected and another 100 matched non-smokers were selected as healthy controls. Blood samples were collected in trisodium citrate anti-coagulant for prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR), analyzed using standard methods (co-agulometer machine) and Ethylenediaminetetraacetic acid for the platelet counts, using an automated haematology analyzer (Sysmex, Tokoyo, Japan).Results:The results showed that the mean platelet counts were significantly lower in the smokers (183x103/cmm±64x103/cmm) versus (244x103/cmm±38x103/cmm) in non-smokers, (p<0.000). Pearson correlation analysis suggested a weak negative correlation between platelet counts with the duration of smoking (r= -0.289, p<0.004) and the age of the smokers (r= -0.238, p<0.017). The mean PT and INR were also significantly lower in smokers (12.9±1.2 seconds) compared with the non-smokers (13.7±1.04 seconds, p<0.000), for PT and (0.95±0.09 versus 1.01±0.08, p<0.000) for INR. In contrast, PTT had no significant variation in smokers (30.5±3.8 seconds) and the non-smokers (37.9±4.6 seconds). A p-value>0.05 was considered significant.Conclusion:Cigarette smokers tend to have lower platelet counts, shorter PT, and INR values, compared to non-smokers. Therefore, smoking might be associated with bleeding disorders but further investigations are needed.

Noradrenaline for reverting hepatorenal syndrome: a prospective, observational, single-center study.

ObjectiveTo evaluate the effectiveness of noradrenaline for the treatment of hepatorenal syndrome (HRS).BackgroundHRS represents the development of renal failure in cirrhotic patients. The standard treatment for HRS is terlipressin, which, as opposed to noradrenaline, is more expensive and less accessible in most tertiary care centers.Patients and methodsThirty consecutive patients with HRS type 1 received noradrenaline (1–4.0 mg/hour) and albumin for 14 days. The parameters recorded were: serum creatinine levels, creatinine clearance, mean arterial pressure (MAP), urine output, and serum sodium levels evaluated at baseline and on treatment days 1, 3, 7, and 14.ResultsMost patients achieved serum creatinine levels <1.5 mg/dL and were considered responders (22/30, 73%), whereas eight patients (27%) were nonresponders. At baseline, responders and nonresponders differed only regarding initial bilirubin levels and international normalized ratio values. Treatment duration was 7.5±3.2 days. Responders experienced a significant (p<0.05) decrease in serum creatinine levels (from 3.26±0.48 to 1.28±0.14 mg/dL), as well as a significant increase (p<0.05) in creatinine clearance (from 21±4.1 to 67.7±12.1 mL/min), urine output (from 583±41.1 to 1163±105 mL/day), MAP (from 79.2±2.94 to 93.9±2.34 mmHg), and serum sodium levels (from 125±2.01 to 132.3±1.39 mEq/L). In nonresponders, the MAP increased, but serum creatinine levels also increased, reflecting a decrease in creatinine clearance and urine output, with no significant change in serum sodium levels over the duration of the treatment.ConclusionIn most patients, noradrenaline treatment induced systemic vasoconstriction resulting in HRS reversal, with acceptable safety, in agreement with previously reported outcomes of terlipressin treatment.

Outcomes Among Patients With Atrial Fibrillation and Appropriate Anticoagulation Control

BackgroundAtrial fibrillation (AF) patients on a vitamin K antagonist (VKA) with time in therapeutic range (TTR) ≥70% are not recommended to switch to a direct oral anticoagulant according to guidelines. ObjectivesThis study sought to assess future TTR and risk of stroke/thromboembolism and major bleeding among AF patients on VKA with TTR ≥70%. MethodsThe authors used Danish nationwide registries to identify AF patients on VKA from 1997 to 2011 with available international normalized ratio values. Patients were included 6 months after VKA initiation, divided according to TTR, and followed for 12 months after inclusion. Cox proportional hazard models estimated hazard ratios (HRs). TTR was examined both as a baseline variable and as a time-dependent covariate in the Cox models. ResultsOf the 4,772 included AF patients still on VKA 6 months after initiation, 1,691 (35.4%) had a TTR ≥70%, and 3,081 (65.6%) had a TTR <70%. Among patients with prior TTR ≥70% still on treatment 12 months after inclusion, only 513 (55.7%) still had a TTR ≥70%. Compared with prior TTR ≥70%, prior TTR <70% was not associated with a higher risk of stroke/thromboembolism (HR: 1.14; 95% confidence interval [CI]: 0.77 to 1.70) or major bleeding (HR: 1.12; 95% CI: 0.84 to 1.49). When the authors estimated TTR time-dependently during follow-up, TTR <70% was associated with an increased risk of stroke/thromboembolism (HR: 1.91; 95% CI: 1.30 to 2.82) and major bleeding (HR: 1.34; 95% CI: 1.02 to 1.76). ConclusionsAmong AF patients on VKA, almost one-half of patients with prior TTR ≥70% had TTR <70% during the following year. Prior TTR ≥70% per se had limited long-term prognostic value.

Renal Dysfunction Affects Anticoagulation Control With Warfarin and Outcomes in Japanese Elderly Patients With Non-Valvular Atrial Fibrillation.

It is unclear whether renal dysfunction affects warfarin control in patients with non-valvular atrial fibrillation (NVAF). Methods and Results: Using a dataset from the J-RHYTHM Registry, time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, and creatinine clearance (CrCl) were determined in elderly patients aged ≥70 years. Target INR values were 1.6-2.6 following Japanese guidelines. Incidences of thromboembolism, major hemorrhage, and all-cause death were determined over 2 years. Of 7,406 NVAF patients enrolled in the registry, 2,782 elderly patients (mean age, 75 years) had data for CrCl measured at baseline and TTR. TTR values were lower in the lower CrCl groups (P<0.001 for trend). CrCl <30 mL/min was independently associated with TTR <65% (odds ratio, 1.49; 95% confidence interval, 1.13-1.95; P=0.004). In the multivariate analysis, TTR <65% was independently associated with thromboembolism (hazard ratio, 2.26; 95% confidence interval, 1.37-3.72; P=0.001), but CrCl was not (CrCl <30 mL/min, 1.68, 0.41-6.85, P=0.473). However, CrCl <30 mL/min and TTR <65% were independently associated with all-cause death (5.32, 1.56-18.18, P=0.008 and 1.60, 1.07-2.38, P=0.022, respectively) and the composite event (thromboembolism, major hemorrhage and all-cause death) (2.03, 1.10-3.76, P=0.024 and 1.58, 1.22-2.04, P=0.001, respectively). Elderly NVAF patients with renal dysfunction had poor warfarin control, which was associated with higher risk of thromboembolism and all-cause death.

How to Generate a More Accurate Laboratory-Based International Normalized Ratio: Solutions to Obtaining or Verifying the Mean Normal Prothrombin Time and International Sensitivity Index.

Although the landscape of anticoagulation therapy is evolving, vitamin K antagonists (VKAs) such as warfarin remain an anticoagulant of choice for many clinicians and their patients. Nevertheless, management of VKA therapy remains challenging, largely because of patient variability and drug and food interactions; thus, VKA dosing has to be personalized. This is achieved by regular monitoring using a test called the prothrombin time (PT), mathematically converted to an international normalized ratio (INR). The INR system is meant to harmonize laboratory test results by taking into account reagent and instrumentation variability that is otherwise expected to give rise to variable PT values, but which should accordingly lead to less variable INR values. Of clinical importance, too low an INR is suggestive of increased thrombotic risk and typically means the VKA dose should be increased, whereas too high an INR is suggestive of increased bleeding risk and typically means the VKA dose should be temporarily withheld and/or decreased. However, evidence continues to show that variability in INR values between laboratories remains unacceptably high. Given that modern instrumentation provides for robust analytical values-meaning highly reproducible intralaboratory clotting times or PTs in this case-the most likely cause of high INR variability is inconsistency in the INR test components-meaning the MNPT (mean normal PT) and ISI (international sensitivity index) values used by laboratories to generate a given INR. In other words, there are doubts as to the accuracy of some INR values because there are corresponding doubts about the accuracy of MNPT and/or ISI values that have been assigned by some laboratories for their reagent/instrument combination. The current report is intended to provide some solutions around the problems of inaccurate INRs, ISIs, and MNPTs, thus aiming to drive laboratory INRs closer to "truth," and thus promote better patient management. The novel strategies include a primary process of transference to obtain/verify MNPT and/or ISI values for a new reagent using an existing reagent as reference, and a secondary process whereby external quality assessment data can be used to correct bias or existing errors in assigned MNPT and/or ISI values.

Clinical Outcomes of Telemonitoring for Patients on Warfarin after Discharge from Hospital.

Objective To evaluate the impact of telephone follow-up service on clinical outcomes in patients on warfarin when discharged from hospital. Methods This randomized controlled trial was conducted at a general hospital in Thailand. Patients aged ≥20 years who were prescribed warfarin when discharged were eligible to participate in this study. They were randomly allocated, using a computer generated random number, to receive either telephone follow-up intervention or usual care. Participants in the intervention group received telephone follow-up by hospital pharmacists for three months. During each telephone call, pharmacists performed medicine use reviews and addressed any problems identified. Key Findings A total of 50 patients participated in this study. The proportion of international normalized ratio (INR) values in the target range for the telephone follow-up group (36/79, 45.6%) was higher than that in the usual care group (19/79, 24.1%), p=0.005. The mean time in the therapeutic range (TTR) in the telephone follow-up group was also higher than that in the usual care group (49.8±34.3 versus 28.0±27.5, p=0.017). All patients in the usual care group experienced one or more out-of-range INR values (25/25, 100%) compared to 21 out of 25 (84%) in the telephone follow-up group, p=0.037. There was no difference between the two groups in the incidence of complications or adverse events associated with warfarin. Conclusions The telephone follow-up service in recently discharged patients helps them achieve and maintain their INR target. This anticoagulant supportive service should be promoted to patients receiving warfarin therapy after discharge. This trial is registered with TCTR20180614006 (Thai Clinical Trials Registry).

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

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

Neither Time in Therapeutic Range nor Most Recent International Normalized Ratio (INR) Correlate with Adverse Events in Patients Supported by Continuous-Flow Left Ventricular Assist Devices

Introduction Continuous-Flow Left Ventricular Assist Devices (CFLVADs) improve mortality and quality of life in end-stage cardiomyopathy patients. Adverse events however remain high. Hypothesis We hypothesize time in therapeutic range (TTR) correlates with adverse events compared to most recent INR. Methods The study group comprised of patients who suffered suspected/confirmed pump thrombosis, stroke or major bleeding event as defined by INTERMACS after ≥ 1 month at home with ≥ 1 month of INR values. Controls (CON) had at least 3 months of INR values after being home for 1 month from LVAD implant and who did not experience any adverse events (AE). Standard statistical methods were employed as indicated: Chi-square, Fishers Exact test, two-sample t-test, Wilcoxon Rank sum test, One way ANOVA and Kruskal Wallis Analysis. Patients with multiple adverse events were excluded. Results From June 2010 - December 2016, 132 patients underwent CFLVAD implantation at our institution who met entry criteria. Mean age was 57±13 yrs and 106 (80%) were male. Seventy-seven (58%) were implanted as bridge to transplant (BTT). There was no statistically significant difference in TTR (p=0.39, Table 1 ) or most recent INR (p=0.33, Table 2 ) prior to AE. Patients who suffered AEs were older than those who did not (59.3± 12 vs. 54.4±14.3 yrs, p=0.04). There was no association of AEs when stratified by gender, LVAD indication, LVAD device type, race, BMI or hospital length of stay (p=ns). Conclusions Neither time in therapeutic range nor most recent INR correlated with major bleeding, neurological dysfunction or pump thrombosis in CFLVAD patients in this analysis. Further investigation beyond strict INR control and anticoagulation is needed to reduce adverse events in this patient population.

Comparative effectiveness evaluation of the improved and conventional perioperative antithrombotic therapy in patients with acute calculous cholecystitis and concomitant ischemic heart disease

The aim — to evaluate the efficacy of improved perioperative antithrombotic therapy in patients who underwent laparoscopic cholecystectomy for acute calculous cholecystitis (ACH) with concomitant ischemic heart disease (IHD).Materials and methods. 168 patients with ACH and IHD who received anticoagulant (ACT) or antiplatelet therapy (APT) before admission to the surgical department of the hospital in Kyiv took part in the study. The comparison group included 95 patients who underwent conventional perioperative antithrombotic therapy, the main group included 73 patients who had bridging therapy according to the developed algorithms. Groups of patients were representative by the functional class of heart failure, angina class, severity and histological form of ACH, the frequency of ACT and APT variants. The target points of the study were the frequency of International Normalized Ratio (INR) therapeutic value achieving or bleeding time (BT) by Lee‑White in the preoperative and early postoperative period and the frequency of hemorrhagic complications.Results and discussion. Immediately before the operation in patients assigned to the main group, the mean INR values were greater than in the comparison group: 2.93 ± 0.18 versus 1.96 ± 0.18. The target values of INR &gt; 2 in the main group were in 18 (90 %) of 20 patients who received warfarin prior to admission, and 11 (52.4 %) of 21 in the comparison group (p = 0.008). Target values of BT &gt; 12 min in the main group were in 48 (90.6 %) of 53 patients who received APT before admission, in the comparison group — in 46 (62.2 %) of 74 (p = 0.001). Statistically significant differences between groups relative to the proportion of patients with therapeutic values of INR and BT were found on the first 3 and 4 days of the postoperative period, respectively. Increased bleeding of the tissues (the bed of the gallbladder), in which stable haemostasis required more than 10 minutes, was observed in 19 (26.0 %) patients in the main group and 20 (21.1 %) in the comparison group (p = 0.449). The need for a tamponade of the gallbladder bed arose respectively in 13 (17.8 %) and 11 (11.6 %) patients (p = 0.253). A decrease in haemoglobin level below 100 g/l, but not lower than 86 g/L, was noted in 4 and 6 patients (all p &lt; 0.05).Conclusions. The improved algorithm of bridging therapy in patients with ACH and concomitant IHD demonstrated a statistically significant increase in the proportion of patients with the target values of the prophylaxis of thromboembolism in the perioperative period (in comparison with the conventional approach) without significant haemorrhagic complications, as in the case of taking anticoagulant or antiplatelet drugs in anamnesis.

Traumatic and spontaneous intracranial hemorrhage in atrial fibrillation patients on warfarin.

Intracranial hemorrhage is the most devastating complication in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC). It can be either spontaneous or caused by head trauma. We sought to address the prevalence, clinical characteristics, and prognosis of traumatic and spontaneous intracranial hemorrhages in AF patients on OAC. Multicenter FibStroke registry of 5,629 patients identified 592 intracranial hemorrhages during warfarin treatment between 2003 and 2012. A large proportion (40%) of intracranial hemorrhages were traumatic. Of these, 64% were subdural hemorrhages (SDHs) and 20% intracerebral hemorrhages (ICHs). With respect to the spontaneous hemorrhages, 25% were SDHs and 67% ICHs. Patients with traumatic hemorrhage were older (81 vs 78 years, p = 0.01) and more often had congestive heart failure (30% vs 16%, p < 0.01) and anemia (7% vs 3%, p = 0.03) compared to patients with spontaneous hemorrhage. Admission international normalized ratio (INR) values (2.7 vs 2.7, p = 0.79), as well as CHA2DS2-VASc (median 4 vs 4, p = 0.08) and HAS-BLED (median 2 vs 2, p = 0.05) scores, were similar between the groups. The 30-day mortality after traumatic hemorrhage was significantly lower than after spontaneous hemorrhage (25% vs 36%, p < 0.01). A significant proportion of intracranial hemorrhages in anticoagulated AF patients were traumatic. Traumatic hemorrhages were predominantly SDHs and less often fatal when compared to spontaneous hemorrhages, which were mainly ICHs. Admission INR values as well as CHA2DS2-VASc and HAS-BLED scores were similar in patients with spontaneous and traumatic intracranial hemorrhage. NCT02146040.

Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants undergoing minor oral surgery or dental extractions.

Individuals on continuous treatment with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) are at increased risk of bleeding complications during and after oral or dental procedures. Anticoagulant treatment is preferably continued at the same dose, since dose reduction or discontinuation of treatment is associated with an increased risk of thromboembolism. The use of haemostatic measures during or after the procedure (or both) could enable continuation of the oral anticoagulant treatment. We aimed to assess the efficacy of antifibrinolytic agents for preventing bleeding complications in people on oral anticoagulants undergoing minor oral surgery or dental extractions. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and the Cochrane Library. Additional searches were performed using ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), the CINAHL database of nursing and allied health services, the open access ProQuest dissertation database, papers and reports from the American College of Clinical Pharmacy (ACCP) and abstract books from annual scientific conferences.Date of last search: 04 January 2018. Randomised and quasi-randomised controlled trials in people on continuous treatment with VKAs or DOACs undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid (TXA) or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained from potentially relevant abstracts and two authors independently assessed these for inclusion based of the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. The quality of the evidence was assessed using GRADE. No eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures were identified.Three randomised trials and one quasi-randomised trial (follow-up in all was seven days) in people on continuous treatment with VKAs were included with a total of 253 participants (mean age 60 years). Two trials published in 1989 and 1993 compared the antifibrinolytic agent TXA with placebo in people using VKAs. Two other trials were published in 1999 and 2015 and compared TXA with gelatin sponge and sutures, and dry gauze compression, respectively. In all included trials, those who were treated with VKAs had international normalised ratio (INR) values within the therapeutic range and TXA was applied locally, not systemically.The two trials from 1989 and 1993 comparing TXA with placebo showed a statistically significant beneficial effect regarding the number of major postoperative bleeding episodes requiring intervention, with a pooled risk difference (RD) of -0.25 (95% confidence interval (CI) -0.36 to -0.14) (128 participants) (moderate-quality evidence). For the two trials that compared TXA with either gelatin sponge and sutures or with dry gauze compression, there was no difference between the TXA and the standard care group, RD 0.02 (95% CI -0.07 to 0.11) (125 participants) (moderate-quality evidence). The combined RD of all included trials was -0.13 (95% CI -0.30 to 0.05) (moderate-quality evidence). There were no side effects of antifibrinolytic therapy that required treatment withdrawal (128 participants) (moderate-quality evidence). Despite heterogeneity between trials with respect to the different haemostatic measures used in the control groups, the trials were comparable regarding design and baseline participant characteristics.Overall, we considered the risk of bias to be low in the trials comparing TXA with placebo and moderate in the trials comparing TXA with alternative haemostatic measures. Based on the results of this Cochrane Review, there seems to be a beneficial effect of locally applied TXA in preventing oral bleeding in people on continuous treatment with VKAs undergoing minor oral surgery or dental extractions. However, the small number of identified randomised controlled trials, the relatively small number of participants included in the trials and the differences in standard therapy and treatment regimens between trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in this population.We were unable to identify any eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures. Therefore, a beneficial effect of antifibrinolytic therapy can currently only be assumed based on data from the people using VKAs.

Extended International Normalized Ratio testing intervals for warfarin‐treated patients

Background A previous single-center randomized trial suggested that patients with stable International Normalized Ratio (INR) values could safely receive INR testing as infrequently as every 12 weeks. Objective To test the success of implementation of an extended INR testing interval for stable warfarin patients in a practice-based, multicenter collaborative of anticoagulation clinics. Methods At six anticoagulation clinics, patients were identified as being eligible for extended INR testing on the basis of prior INR value stability and minimal warfarin dose changes between 2014 and 2016. We assessed the frequency with which anticoagulation clinic providers recommended an extended INR testing interval (> 5 weeks) to eligible patients. We also explored safety outcomes for eligible patients, including next INR values, bleeding events, and emergency department visits. Results At least one eligible period for extended INR testing was identified in 890 of 3362 (26.5%) warfarin-treated patients. Overall, the use of extended INR testing in eligible patients increased from 41.8% in the first quarter of 2014 to 69.3% in the fourth quarter of 2016. The number of subsequent out-of-range next INR values were similar between eligible patients who did and did not have an extended INR testing interval (27.3% versus 28.4%, respectively). The numbers of major bleeding events were not different between the two groups, but rates of clinically relevant non-major bleeding (0.02 per 100 patient-years versus 0.09 per 100 patient-years) and emergency department visits (0.07 per 100 patient-years versus 0.19 per 100 patient-years) were lower for eligible patients with extended INR testing intervals than for those with non-extended INR testing intervals. Conclusions Extended INR testing for stable warfarin patients can be successfully and safely implemented in diverse, practice-based anticoagulation clinic settings.

Outcomes of warfarin therapy managed by pharmacists via hospital anticoagulation clinic versus online anticoagulation clinic

Background In response to the recognized difficulty in the management of patients on anticoagulation therapy, anticoagulation management services were developed in both hospital anticoagulation clinics (HACs) and an online anticoagulation clinic (OAC) by a pharmacist. Objective To compare monitoring outcomes and complications of warfarin therapy managed by pharmacists via hospitaloron-line. Setting The anticoagulation clinic of Fujian Medical University Union Hospital, China. Method A retrospective, observational cohort study was used to compare patients managed via hospital to those managed o-line between December 2015 and 2016. The primary outcome was the percentage of time in the therapeutic range (TTR). The secondary outcomes were the incidence rates of hemorrhagic events, thrombotic events and extreme international normalized ratio (INR) values. Results A total of 152 patients were evaluated; 70 patients managed in a HAC were compared to 82 patients managed via an OAC. There were no significant differences in the TTR (78.9 vs. 74.0%, P = 0.393) and adverse events [major bleeding events (0 vs. 1.2%, P = 1.000), minor bleeding events (10.0 vs. 9.8%, P = 0.960), thromboembolic events (0 vs. 0%, P = 1.000), warfarin-related emergency visits (2.9 vs. 3.7%, P = 1.000)], warfarin-related hospital admissions (0 vs. 1.2%, P = 1.000), and the incidence of subtherapeutic (3.0 vs. 3.8%, P = 0.148), and extreme total (8.4 vs. 5.8%, P = 0.135), between the groups managed via HAC and OAC. Patients managed in the HAC were more stable on warfarin, with a higher percentage of INR values within the target therapeutic range (80.2 vs. 71.9%, P = 0.005) and a lower incidence of supratherapeutic INR values (8.4 vs. 18.5%, P = 0.001) compared to patients managed via OAC. Conclusion The management of oral anticoagulation therapyon-line yielded similar clinical outcomes compared to that achieved by managementvia the hospital, although the incidence of supra-therapeutic INR values was increased.

Razón internacional normalizada y mortalidad de los pacientes con insuficiencia cardiaca y fibrilación auricular tratados con antagonistas de la vitamina K

Introduction and objectivesHeart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up. MethodsIn this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality. ResultsDuring a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years’ follow-up: –0.50; 95%CI, –0.77 to –0.23 years; P < .001; and –0.40; 95%CI, –0.70 to –0.11 years; P = .007, respectively, compared with INR 2-3. ConclusionsIn acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk.

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

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

Time in Therapeutic Range of Oral Vitamin K Antagonists in Hospitalized Elderly Patients.

Oral vitamin K antagonists (VKAs) are commonly used in older adults. To ensure the efficiency and safety of these drugs, the international normalized ratio (INR) must be monitored. The time in therapeutic range (TTR) is an internationally recommendedassessment of the anticoagulation quality. Our study aimed to assess the TTR of VKAs in a hospitalized geriatric population and identify factors associated with low TTR. This was a multicenter retrospective study of data from 1899 patients with a mean age of 87 years between 2013 and 2015 in the geriatric units of four French hospitals. The data collection consisted of 2450 VKA prescriptions. We excluded prescriptions with a duration of < 7days, monitoring with fewer than two INR values and patients with prosthetic heart valves. TTR was assessed using the Rosendaal method. Factors associated with a low TTR (<50%) were assessed using a non-parametric method. The mean TTR observed in this population was 42.6%. The TTR was <50% for 62.5% of the patients included in this study. Significant associations were found between TTR < 50% and aspartate transaminase (AST), alkaline phosphatase (ALT), thyroid-stimulating hormone (TSH), prescription duration, fluconazole instauration, hemoglobin, and C-reactive protein (CRP). Both our results and those in the literature indicate that TTR in geriatric populations is lower than that in the general population. Most patients had an insufficient TTR, exposing them to an increased risk of thromboembolic and hemorrhagic events. These data provide a perspective on poor-quality anticoagulation and illustrates the difficulty of using VKAs in geriatric patients.