Subtherapeutic International Normalized Ratio Research Articles

Antiphospholipid Antibody Syndrome (APS) Pediatric Patient Outcomes on Warfarin

Background: Antiphospholipid antibody syndrome (APS) is an acquired thromboembolism (TE) risk factor and places patients at very high risk of recurrent TE. APS diagnosis requires venous (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or arterial thromboembolism and laboratory diagnosis including persistently positive lupus anticoagulant (LA) or elevated anticardiolipin (aCL) and/or beta 2 glycoprotein I (B2GPI) antibodies tested 12 weeks apart. Vitamin K antagonist (warfarin) is the standard of care anticoagulant to reduce risk of TE recurrence in APS patients. Warfarin is dosed based on the International Normalized Ratio (INR) with established therapeutic ranges for optimal efficacy and safety. The reported time in therapeutic range (TTR) varies greatly across specialties with an average TTR of 50-55%. However, it is often difficult to maintain target INR in APS. Furthermore, there is limited data evaluating pediatric patients with APS and their TTR on warfarin and outcomes. Aim: To evaluate the relationship of APS status to TTR and outcomes of patients < 21 years of age with APS who are on warfarin anticoagulation. Methods: This was a single center analysis of APS patients between July 2019 and May 2022 who were enrolled in a multi-center prospective study of pediatric patients on warfarin therapy, eKITE (electronic KidClot Thrombophilia Education). The study included an online learning series regarding warfarin management. Home INR meters and test strips were provided to all patients to perform INR testing. INR values were reported by patients and recorded. Demographic and clinical data was extracted from the electronic medical record, target INR was set by the treating provider, and TTR was calculated as a surrogate for safe, effective warfarin management. Results: Nine patients (n=9) with APS were identified for this analysis, mean age 16.7 years (range 12-19 years). Demographic and laboratory findings are summarized in Table 1. Most patients had secondary APS due to systemic lupus erythematous (SLE) 78% (n=7) and 22% (n=2) had other primary diagnoses. APS antibody status included single positive in 67% (n=6), double positive in 22% (n=2), and triple positive in 11% (n=1). More specifically, APS criteria were met by persistently elevated LA in 78% (n=7), aCL IgM in 22% (n=2) with overall mean aCL IgM of 34.4 MPL^ (range 9.9-127.9), B2GPI IgG in 11% (n=1) with overall mean B2GPI IgG SGU* of 13.1 (range 0.9-63.3), and B2GPI IgM in 22% (n=2) with overall B2GPI IgM mean of 32.5 SGU (range 3.3-190.9). At time of presentation 67% (n=6) of patients had DVT, 44% (n=4) had PE, 11% (n=1) had arterial TE, and 22% (n=2) presented with DVT & PE. Mean TTR for all patients was 56%. TTR for single positive APS was 66%, double positive APS 39%, and triple positive APS 33%. TTR for secondary APS (SLE) and non-SLE diagnoses was 53% and 68% respectively. Mean dose changes were 11 (range 0-48) with one single positive LA patient requiring 48 dose changes, and two patients with single positive LA not requiring any dose changes. Two patients (22%) developed recurrent clot. One triple positive APS patient developed two DVTs and one non-SLE patient developed recurrent arterial TE. Three patients (33%) had minor bleeding events including mild epistaxis and hematemesis not requiring intervention. One patient (11%) had a major bleeding event, hemoperitoneum from pseudoaneurysm extravasation, while resuming warfarin during post-operative period, and required takeback surgery with sub-therapeutic INR 1.5 at the time of event. Conclusion: The mean TTR for pediatric patients with APS is similar to what is reported in other populations despite the challenge of managing warfarin in this group where the INR may be affected by primary disease modifying medications or disease flares. The risk of recurrent TE remains high in APS patients. Home INR monitors are a safe and effective strategy in managing warfarin anticoagulation in APS patients, reducing time and laboratory monitoring burden for frequent dose changes, which ultimately improves quality of life.Optimizing TTR is important to decrease risk of recurrent TE or bleeding in these high risk APS patients.

Anticoagulation Bridging in Patients With Left Ventricular Assist Device: A Regional Analysis of HeartMate 3 Recipients.

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.

Incidence of Prosthetic Valvular Thrombosis in Rheumatic Heart Valve Diseases and Risk Factors for Mortality: Experience from a Tertiary Care Center with Review of Management Options

Background Prosthetic valve thrombosis bears significant risks of morbidity and mortality. In our study, we explore the risk factors associated with thrombolysis for thrombosis of prosthetic valves of the heart. Materials and Methods This is a hospital-based cross-sectional study with 60 patients with valve replacement between 25 and 60 years. Using an organized questionnaire we have obtained data on sociodemographic, behavioral risk factors, and previous history of other medical conditions. Results and Discussion The incidence of prosthetic valve thrombosis was 4% ( n = 60). The prevalence of aortic valve thrombosis was found to be 3.4% and mitral valve thrombosis was 5.2%. The mean age group of the study population was 30 ± 10 years. The incidence was highest (31%) in the 30–40 years age group. Aortic valve thrombosis was the most common ( n = 48, 80%). The overall mortality was 38% ( n = 23). The mortality rate due to Aortic valve and Mitral valvar thrombosis was 41.06% ( n = 20) and 20% ( n = 3), respectively. Sub-therapeutic international normalized ratio (INR) was noted in 86% ( n = 52) patients and drug non-compliance was 70% ( n = 42). All patients underwent thrombolysis, considering the higher severity of functional class. The risk factors significant for mortality were previous history of valve thrombosis, subtherapeutic INR and aortic valve. Conclusions Aoretic valve prosthetic valve thrombosis was the most common and the overall mortality was higher in women. High mortality was observed in the cohort. Previous history of thrombosis and subtherapeutic INR is an important risk factor for mortality.

Dicloxacillin-Warfarin Drug-Drug Interaction - A Register-Based Study and In Vitro Investigations in 3D Spheroid Primary Human Hepatocytes.

Dicloxacillin is used to treat staphylococcal infections and we have previously shown that dicloxacillin is an inducer of cytochrome P450 enzymes (CYPs). Here, we employed a translational approach to investigate the effect of a treatment with dicloxacillin on warfarin efficacy in Danish registries. Furthermore, we assessed dicloxacillin as an inducer of CYPs in vitro. We conducted a register-based study and analyzed international normalized ratio (INR) levels in chronic warfarin users before and after short- and long-term use of dicloxacillin (n=1023) and flucloxacillin (n=123). Induction of CYPs were investigated in a novel liver model of 3D spheroid primary human hepatocytes (PHHs) at the level of mRNA, and protein and enzyme activity. Short- and long-term dicloxacillin treatments decreased INR levels by -0.65 (95% CI: -0.57 to -0.74) and -0.76 (95% CI: -0.50 to -1.02), respectively. More than 90% of individuals experienced subtherapeutic INR levels (below 2) after long-term dicloxacillin treatment. Flucloxacillin decreased INR levels by -0.37 (95% CI: -0.14 to -0.60). In 3D spheroid PHHs, the maximal induction of CYP3A4 mRNA, protein and enzyme activity by dicloxacillin were 4.9-, 2.9- and 2.4-fold, respectively. Dicloxacillin also induced CYP2C9 mRNA by 1.7-fold. Dicloxacillin induces CYP enzymes and reduces the clinical efficacy of warfarin in patients. This effect is substantially exacerbated during long-term treatment with dicloxacillin. The in vitro results corroborated this drug-drug interaction and correlated to the clinical findings. Caution is warranted for warfarin patients that initiate dicloxacillin or flucloxacillin, especially for a long-term treatment of endocarditis.

Medication adverse events in the ambulatory setting: A mixed-methods analysis.

To characterize ambulatory care adverse drug events reported to the Collaborative Healthcare Patient Safety Organization (CHPSO), a network of 400 hospitals across the United States, and identify addressable contributing factors. We abstracted deidentified ambulatory care CHPSO reports compiled from May 2012 to October 2018 that included medication-related adverse events to identify implicated medications and contributing factors. We dual-coded 20% of the sample. We quantitatively calculated co-occurring frequent item sets of contributing factors and then applied a qualitative thematic analysis of co-occurring sets of contributing factors for each drug class using an inductive analytic approach to develop formal themes. Of 1,244 events in the sample, 208 were medication related. The most commonly implicated medication classes were anticoagulants (n = 97, or 46% of events), antibiotics (n = 24, 11%), hypoglycemics (n = 19, 9%), and opioids (n = 17, 8%). For anticoagulants, timely follow-up on supratherapeutic international normalized ratio (INR) values occurred before the development of symptoms. Incident reports citing antibiotics often described prescribing errors and failure to review clinical contraindications. Reports citing hypoglycemic drugs described low blood sugar events due to a lack of patient education or communication. Reports citing opioids described drug-drug interactions, commonly involving benzodiazepines. Ambulatory care prescribing clinicians and community pharmacists have the potential to mitigate harm related to anticoagulants, antibiotics, hypoglycemics, and opioids. Recommendations include increased follow-up for subtherapeutic INRs, improved medical record integration and chart review for antibiotic prescriptions, enhanced patient education regarding hypoglycemics, and alerts to dissuade coprescription of opioids and benzodiazepines.

Pharmacist-Managed Anticoagulation Services for Warfarin Management in Tertiary Hospitals: The Egyptian Experience

Background: Warfarin is widely regarded as the main anticoagulant in lowering the risk of thromboembolism. This study used indicators to compare pharmacist-managed anticoagulation services, using a well-prepared protocol, with physician-managed anticoagulation services. Methods: A retrospective prospective pilot study was conducted to compare patient outcomes before and after transitioning patients to pharmacist-managed anticoagulation services, comparing the proportion of those with therapeutic international normalized ratio (INR), subtherapeutic INR, and supratherapeutic INR, as well as their bleeding occurrences as indicators of assuring quality care. Results: A significant improvement in anticoagulation management was noted in the transition to pharmacist-managed anticoagulation services. The proportion of those with subtherapeutic INR decreased from 61.8% to 11.8% (p &lt; 0.001), those with supratherapeutic INR decreased from 20.6% to 2.9% (p &lt; 0.001), those with therapeutic INR increased from 17.6% to 85.3% (p &lt; 0.001), and the occurrence of bleeding decreased from 11.8% to 0.0%, without significant difference in warfarin doses (median from 4 before the transition to 5 after); in addition, the time to reach therapeutic INR decreased from 12-24 weeks to 2-8 weeks after transitioning to pharmacist-managed anticoagulation services. Conclusion: Pharmacist-managed anticoagulation services are considered safer and more effective than physician-managed anticoagulation services alone in terms of patients’ adherence and satisfaction, which provide an excellent opportunity for quality assurance care.

Association between time to therapeutic INR and length of stay following mechanical heart valve surgery

Warfarin is the only oral anticoagulant approved for use following mechanical valve surgery (MeVS). Patients may experience prolonged hospital length of stay (LOS) following MeVS awaiting an appropriate warfarin effect. We aimed to determine whether an association exists between time to achieve the first therapeutic international normalized ratio (INR) and LOS following MeVS. Retrospective single center cohort study. We included consecutive adult patients undergoing elective MeVS from 2013 to 2018. Landmark analyses and multivariable regression with time-updated INR were used to estimate the association between time to therapeutic INR (TTI) and LOS. Among 384 patients (median age: 51 years, interquartile range [IQR]: 41-57; 58.3% male), the median TTI was 4 days (IQR: 2-5). Thirty seven percent of patients were discharged with a subtherapeutic INR, many on bridging anticoagulation or with an INR close to target. Those achieving therapeutic INR had an increased rate of hospital discharge (adjusted hazard ratio: 2.17; 95% confidence interval: 1.71-2.76; p < .0001). Attainment of a therapeutic INR anytime between postoperative Days 4 and 13 was significantly associated with a shorter LOS. Prolonged time to achieve a therapeutic INR was independently associated with prolonged LOS. Future strategies aimed at improving attainment of therapeutic INR following MeVS may reduce hospital LOS.

Drive-up INR testing and phone-based consultations service during COVID-19 pandemic in a pharmacist-lead anticoagulation clinic in Qatar: Monitoring, clinical, resource utilization, and patient- oriented outcomes.

BackgroundCoronavirus disease 2019 (COVID‐19) pandemic has resulted in unprecedented pressure on healthcare systems and led to widespread utilization of telemedicine or telehealth services. Combined with teleclinics, using drive‐up fingerstick International normalized ratio (INR) testing was recommended to decrease exposure risk of anticoagulation patients.ObjectiveTo evaluate the impact of transitioning from clinic‐based anticoagulation management services to drive‐up and phone‐based services during COVID‐19 pandemic in Qatar.MethodsThe study comprised of two components: a retrospective cohort study of all eligible patients who attended anticoagulation clinic over 1‐year period (6 months before and 6 months after service transition) and a cross‐sectional survey of eligible patients who agreed to provide data about their satisfaction with the new service. Monitoring parameters, clinical outcomes, and resource utilization related to warfarin therapy were compared before and after service transition. Patients' experience was explored through a structured survey.ResultsThere was no statistically significant difference between clinic‐based and phone‐based anticoagulation services in mean time and number of visits within therapeutic range (P = .67; P = .06 respectively); mean number of extreme subtherapeutic and supratherapeutic INR values (P = .32 and P = .34, respectively); incidence of thromboembolic complications and warfarin related hospitalization. There was one reported bleeding and one emergency visit (0.9%) in the phone‐based group vs none in the clinic‐based group. Frequency of INR testing and compliance to attending clinics appointments declined significantly (P = .002; P = .001, respectively). Overall, patients were highly satisfied with the new service. The majority of patients found it better (51.6%) or just as good as the traditional service (44.5%). Patients who preferred the new service were significantly younger than their counterparts (P = .005).ConclusionThe service of drive‐up INR testing and phone‐based consultations was shown to be comparable to traditional anticoagulation service, a finding that supports maintaining such services as part of the new normal after the pandemic is over.

Gastrointestinal Bleeding, International Normalized Ratio, and Subsequent Risk of Recurrent Thromboembolic Events among Left Ventricular Assist Device Patients

Purpose Patients have an increased risk of gastrointestinal bleeding (GIB) and thromboembolic events (TE) after left ventricular assist device (LVAD) implantation. We hypothesized that GIB in LVAD recipients leads to low international normalized ratio (INR) values that may predispose to increased risk of TE. Methods This study included 410 patients in the University of Rochester Medical Center LVAD Database who were implanted between 2008 and 2020 (mean age 56 ± 13 years, 80% male, 84% white). Longitudinal data on INR was categorized as therapeutic (2-3), sub-therapeutic ( 3). A TE event was defined as device malfunction, confirmed or suspected pump thrombosis, ischemic stroke, transient ischemic attack, venous thromboembolism, or arterial non-CNS thromboembolism. The primary outcome was recurrent TE. The Anderson-Gill recurrent regression analysis was used to obtain hazard ratios and confidence intervals. Results During median follow-up of 2.07 years 83 (20%) patients had TE. After multivariate adjustment, GIB was associated with a 28% increased likelihood for subsequent sub-therapeutic INR values ( Conclusion Our findings suggest that the occurrence of GIB following LVAD implantation may predispose to increased risk of recurrent TE through sub-therapeutic INR values. INR

Effectiveness of the Alfalfa App in Warfarin Therapy Management for Patients Undergoing Venous Thrombosis Prevention and Treatment: Cohort Study.

BackgroundOver the years, the internet has enabled considerable progress in the management of chronic diseases, especially hypertension and diabetes. It also provides novel opportunities in online anticoagulation management. Nevertheless, there is insufficient evidence regarding the effectiveness of online anticoagulation management.ObjectiveThis study explored the effectiveness and safety of warfarin management via the Alfalfa app, so as to provide evidence in support of anticoagulant management through online services.MethodsIn this retrospective, observational cohort study, 824 patients were included. In the offline group, patients went to the hospital clinic for warfarin management. In the Alfalfa app group, patients reported the dose of warfarin, current international normalized ratio (INR) value, and other related information through the Alfalfa app. Physicians or pharmacists used the app to adjust the dose of warfarin and determined the time for the next blood INR testing. Patients completed INR testing by point-of-care at home or hospital. The primary outcome of the study was the percentage of time in therapeutic range (TTR). Secondary outcomes included minor and major bleeding events, thrombotic events, warfarin-related emergency department visits, hospital admissions, and high INR values.ResultsThe TTR and percentage of INR values in the range were significantly higher in the Alfalfa app group than in the offline group (79.35% vs 52.38%, P<.001; 3314/4282, 77.39% vs 2005/4202, 47.72%, P<.001, respectively). Patients managed via the Alfalfa app had lower rates of subtherapeutic (172/4282, 4.02% vs 388/4202, 9.23%; P<.001), supratherapeutic (487/4282, 11.37% vs 882/4202, 20.99%; P<.001), and extreme subtherapeutic INR values (290/4282, 6.77% vs 910/4202, 21.66%; P<.001). Additionally, the Alfalfa app group had lower incidences of major bleeding (2/425, 0.5% vs 12/399, 3.0%; P=.005), warfarin-related emergency department visits (13/425, 3.1% vs 37/399, 9.3%; P<.001), and hospital admissions (1/425, 0.2% vs 12/399, 3.0%; P=.001) compared with the offline group. However, the Alfalfa app group had a higher incidence of minor bleeding than the offline group (45/425, 10.6% vs 20/399, 5.0%; P=.003). There were similar incidences in extreme supratherapeutic INR values (19/4282, 0.44% vs 17/4202, 0.40%; P=.78) and thromboembolic events (1/425, 0.2% vs 1/399, 0.3%; P=.53) between the two groups.ConclusionsWarfarin management is superior via the Alfalfa app than via offline services in terms of major bleeding events, warfarin-related emergency department visits, and hospital admissions.

Enoxaparin Use and Adverse Events in Outpatients With a Continuous Flow Left Ventricular Assist Device at a Single Institution

Background: Patients with left ventricular assist devices (LVADs) are anticoagulated with warfarin and may receive enoxaparin bridging for a subtherapeutic international normalized ratio (INR). There is no guideline regarding enoxaparin bridging in LVAD patients and a dosing strategy to ensure efficacy and safety is uncertain. Objective: The objective was to characterize the use of enoxaparin bridging for subtherapeutic INRs and its impact on thrombotic or major bleeding events (MBE) in patients with an LVAD. Methods: A retrospective review from 6/1/17 to 6/30/18 was performed. Patients with an LVAD were excluded if they had less than 60 days of outpatient anticoagulation or age <18 years old. Patients were divided into 2 cohorts based on enoxaparin exposure. MBE and thrombotic events were classified as related to enoxaparin if events occurred while receiving enoxaparin and up to 7 days or 30 days, respectively, after discontinuation. Results: Seventy-one LVAD patients met inclusion criteria and 50 patients received enoxaparin bridging. Therapeutic-dose enoxaparin was initiated at a mean INR of 1.8 for a mean duration of 2.8 days. In the enoxaparin exposure group, one MBE occurred 6 days after enoxaparin discontinuation, coinciding with an INR increase from 1.8 to 4.7. One thrombotic event occurred 2 days after enoxaparin discontinuation at an INR of 5.0. Conclusion: This institution’s bridging strategy of therapeutic-dose enoxaparin with a short duration has a low rate of bleeding and thrombotic events. Additional prospective studies of anticoagulation bridging based on characteristics such as type of LVAD device are warranted.

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR

IntroductionCurrent guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. MethodsPatients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. ResultsNo significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. ConclusionAdministration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.

Safety of thrombolytic therapy in patients with prosthetic heart valve thrombosis who have high international normalized ratio levels.

Prosthetic valve thrombosis (PVT) is a rare but life-threatening complication of heart valve replacement. Based on the current guidelines, the treatment of a large number of these patients could be performed through the administration of thrombolytic agents. In the present study, we aim to assess the safety of thrombolytic therapy in patients with PVT who have high international normalized ratio (INR) levels. In this study, we retrospectively analyzed outcomes of thrombolytic therapy in 65 PVT patients with different levels of INR at the time of fibrinolysis at a tertiary cardiac center. Mean age of patients was 51.6 ± 12.47 years. The tricuspid valve was the most common site of prosthetic valve thrombosis (64.6%). The Median (range) of INR was 2.1 (0.9-4.9). The majority of patients (50.8%) achieved a complete response following thrombolytic treatment. There were no cases of intracranial hemorrhage. Other major and minor bleedings occurred in 3 (4.6%) and 10 (15.4%) patients, respectively. No embolic stroke and systemic embolism were observed. We found no significant difference in the frequency of major (P-value = .809) and minor (P-value = .483) bleeding as well as response to thrombolytic therapy (P-value = .658) between patients with different levels of INR. Total administered dose of Streptokinase was also similar in PVT patients with or without major (P-value = .467) and minor (P-value = .221) bleeding complications. We concluded that there was no significant difference between PVT patients presenting with subtherapeutic and high INR levels who received thrombolytic treatments regarding both minor and major bleeding complications as well as response to thrombolysis.

Relationship between initial international normalized ratio and prognosis in patients with cardiogenic cerebral embolism

Cardiogenic cerebral embolism is one of the most common causes of ischemic stroke. In general, cardioembolic stroke is associated with more severe neurological deficits and higher early mortality, as well as a worse functional outcome. Oral anticoagulant (OAC) therapy could reduce the risk of stroke significantly. However, several limitations have led to it being underused, which raises the failure of anticoagulant therapy. This study aimed to investigate the patients with atrial fibrillation presented cardioembolic stroke who underwent OAC therapy, and to assess treatment efficacy, and outcomes, especially the international normalized ratio (INR) value in the acute phase. Clinical data of 306 patients with cardioembolic stroke and etiology of atrial fibrillation were retrospectively analyzed, and demographics, cardiovascular risk factors, embolic cardiopathy, CHADS2 and CHA2DS2-VASc score, HAS-BLED score, INR value, TOAST subtypes, OCSP classification, modified Rankin Scale (mRS) scores and prognosis were evaluated. The median score on the CHADS2 and CHA2DS2-VASc scales was 3 and 4, respectively; The median score on the HAS-BLED scale was 2. Only 33 patients (10.8%) were in therapeutic INR range at the onset of stroke. In the acute phase, 233 patients (76.1%) continued to use OAC therapy, and 73 patients were suspended. Eighteen patients (24.7%) resumed treatment after an average of 32 days. Thirty-nine of 251 survivors with nonvalvular atrial fibrillation were modified to novel oral anticoagulants (NOACs). At 3 months follow-up, patients with INR ≥1.7 had significantly better prognosis than those with INR <1.7, both in the percentage of patients with functional independence (78.9% vs. 41.2%) and in mortality (7.0% vs. 25.0%) (P<0.001). Patients presented cardioembolic stroke despite being treated with OAC, especially those with a subtherapeutic INR value, raises the failure of anticoagulant therapy. Despite the ineffectiveness of the OAC, the prognosis is better when the INR ≥1.7 at the initiation of the stroke.

Effect of Temporary Interruption of Warfarin Due to an Intervention on Downstream Time in Therapeutic Range in Patients With Atrial Fibrillation (from ORBIT AF)

The aim of this study was to quantify time in therapeutic range (TTR) before and after a temporary interruption of warfarin due to an intervention in the Outcomes Registry for Better Informed Treatment of atrial fibrillation (AF). AF patients on warfarin who had a temporary interruption followed by resumption were identified. A nonparametric method for estimating survival functions for interval censored data was used to examine the first therapeutic International Normalized Ratio (INR) after interruption. TTR was compared using Wilcoxon signed rank test. Cox proportional hazards model was used to investigate the association between TTR in the first 3 months after interruption and subsequent outcomes at 3 to 9 months. Of 9,749 AF patients, 71% were on warfarin. Over a median (IQR) follow-up of 2.6 (1.8 to 3.1) y, 33% of patients had a total of 3,022 temporary interruptions. The first therapeutic INR was recorded within 1 week in 35.0% (95% confidence interval 32.6% to 37.4%), 2 weeks in 54.6% (52.2% to 57.0%), 30 days in 70.0% (67.9% to 72.1%) and 90 days in 91.3% (90.0% to 92.5%) of patients. Compared with pre-interruption, TTR 3 months after interruption was significantly lower (61.1% [36.6% to 85.0%] vs 67.6% [50.0% to 81.3%], p <0.0001). A 10 unit increment in the TTR in the first 3 months after interruption was associated with a lower risk of major bleeding [Hazard ratio 0.91 (0.85 to 0.97), p = 0.005]. This association was noted in patients who received bridging anticoagulation, but not in those who did not. In conclusion, temporary interruption of warfarin is common, and nearly half of these patients had subtherapeutic INR after 2 weeks. Lower TTR in the first 3 months after interruption was associated with higher incidence of major bleeding in patients who received bridging anticoagulation.

Iliopsoas Hematoma in Warfarin Treatment: Case Report and Review of Literature

Iliopsoas hematoma is a rare complication in patients on warfarin and usually presents as lower abdominal, groin or thigh pain. The author presents a case of spontaneous iliopsoas hematoma in an 89-year-old female that was initially suspected to be a hip fracture. A review of 12 case reports on iliopsoas hematoma in patients on warfarin shows that the mean age of reported cases was 72 years. Patients present with lower abdominal, groin, flank or thigh pain (100%), lower extremity weakness and/or difficulty in walking (50%) and loss of or abnormal sensation in the lower extremity (17%). Forty two percent of the hematoma cases were in patients with therapeutic or sub-therapeutic international normalized ratio (INR). Iliopsoas hematoma should be considered in elderly patients on warfarin who present with lower abdominal or groin pain, even in patients with therapeutic or sub-therapeutic INR.

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.

Ischaemic stroke and transient ischaemic attack on anticoagulants: outcomes in the era of direct oral anticoagulants

Clinical and imaging characteristics of patients receiving direct oral anticoagulants presenting with transient ischaemic attack or stroke are lacking. A retrospective review of all patients who presented to a high-volume primary stroke centre with acute stroke symptoms while prescribed an oral anticoagulant between January 2012 and June 2017. Clinical, radiological characteristics and functional outcomes were examined. Anticoagulated patients diagnosed with stroke or transient ischaemic attack shared similar disease and outcome characteristics irrespective of anticoagulants used. One-third of warfarin patients with sub-therapeutic international normalised ratios were treated with thrombolytics but no direct oral anticoagulants level was performed in any of the patients, with only one treated by intravenous thrombolysis.

Relationship between silent cerebral infarcts and quality of anticoagulation in patients with prosthetic mitral valves.

Although patients with prosthetic heart valves have an increased risk of clinically overt cerebrovascular events, evidence for the risk of silent cerebral infarction (SCI) is scarce. Serum neuron-specific enolase (NSE) is suggested to be a valid biomarker that allows for the quantification of the degree of neuronal injury. We aimed to assess whether NSE is elevated as a marker of recent SCI in patients with a prosthetic mitral valve. We measured the NSE levels in 103 patients with a prosthetic mitral valve (PMV), admitted to our outpatient clinics for routine evaluation. International normalized ratio (INR) and time in target therapeutic range (TTR) were noted as anticoagulation quality measures. Most of the patients were females (58%), and a mean age was 65 years. NSE values of >12 ng/mL, suggesting a recent SCI, was detected in 25 patients (24%). NSE was negatively correlated with admission INR (r=-0.307, p=0.002). Multivariate analyses demonstrated subtherapeutic INR (INR <2.5) and suboptimal TTR as independent predictors of SCI [odds ratio (OR) 5.420; 95% confidence interval (CI) 1.589 to 18.483; p=0.007, and OR 4.149; 95% CI 1.019 to 16.949; p=0.047, respectively]. Being a current smoker (OR 10.798; 95% CI 2.520 to 46.272; p=0.001), large left atrium (OR 6.763; 95% CI 2.253 to 20.302; p=0.001), and not using aspirin (OR 10.526; 95% CI 1.298 to 83.333; p=0.027) were other independent predictors. Our data suggest that silent brain infarcts are very prevalent among patients with a PMV, as one fourth of them had the event during their routine outpatient visit. Poor quality of anticoagulation partly explains the increased prevalence.

Anticoagulation with Warfarin: Roles of Adherence, Social Support and Illness Perception.

This study was aimed to determine (1) the associations between adherence to warfarin, social support, perception of illness, and demographic factors on the quality of international normalized ratios (INRs); as well as (2) the relationship between the patients' scores in the Malaysian medication adherence scale (MALMAS) and their current INRs. This cross-sectional survey was conducted from November 2017 to January 2018 at the warfarin clinic of Jerantut Hospital, Malaysia. Some 58 participants were recruited, of whom 70.7% were diagnosed with atrial fibrillation (AF). Overall, 87.9% of the participants claimed adherence to their warfarin regimens. Patients with good-quality INR therapy were significantly older, had a higher median income and longer appointment durations. In terms of illness perception (IP), participants with good-quality INR therapyhad significantly lower scores in the identity, personal control, and consequence domains. Overall, the total scores for IP were significantly lower in the good-quality INR therapy. Meanwhile, the MALMAS scores were significantly lower in patients with sub-therapeutic current INR. However, there were no associations between warfarin adherence and perceived social support with current TTR. Monitoring of demographic factors and IP's domains is vital since they were associated with quality of INR therapy. Meanwhile, the occurrence of sub-therapeutic current INR should raise suspicion of poor adherence in these patients. Overall, IP and MALMAS are useful tools that should be integrated into the patient care protocols.