Minor Bleeding Events Research Articles

Warfarin and food, herbal or dietary supplement interactions: A systematic review.

To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin. A systematic literature review was performed on 5 databases from inception up to 31 December 2019. These interactions were classified depending on the likelihood of interaction and supporting evidences. A total of 149 articles describing 78 herbs, food or dietary supplements were reported to interact with warfarin. These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics. Twenty unique herb and dietary supplements also reported to result in minor bleeding events, such as purpura and gum bleeding as well as major events such as intracranial bleeding that led to death. While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs. These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St. John's Wort, sushi and smoking tobacco. Patients should be counselled to continue to seek advice from their healthcare professionals when starting any new herbs, food or supplement.

Factors associated with bleeding events in patients on rivaroxaban for non-valvular atrial fibrillation: A real-world experience

BackgroundRivaroxaban is a direct oral anticoagulant (DOAC) approved for the treatment of non-valvular atrial fibrillation (NVAF). Data related to the risk factors associated with rivaroxaban-induced bleeding in patients with NVAF remain scarce in the community setting. We sought to investigate these bleeding risk factors in a racially diverse patient population. MethodsWe conducted a single-center, retrospective study based on a chart review of patients who received rivaroxaban from our outpatient pharmacy from January 2015 to April 2018 for NVAF. Any reported bleeding event (BE) was recorded as either major or minor bleeding event. Demographic and clinical data were collected and analyzed. ResultsOf the 327 patients included in our analysis, 105 (32%) were female, and the mean age was 62 ± 12 years. Among the included patients, 176 (54%) patients were black, 71 (22%) were white, 51 (15.6%) were Hispanic, 13 (4%) were Asian, and 15 (4.6%) belonged to other races. 89 (27.2%) of the patients had co-prescription of aspirin. A total of 24 (7.3%) patients developed BE, out of which 9 (2.7%) patients had a major BE, and 15 (4.5%) patients had minor BE. Non-fatal gastrointestinal bleeding and epistaxis were the most common type of BE. On multivariable analysis, concurrent aspirin use (81 to 325 mg) (P = 0.03; odds ratio (OR) 2.60 [1.08–6.28]) and increasing age (P = 0.00; OR 1.06 [1.01–1.11]) were independent predictors of BE. ConclusionIn community practice, aspirin co-prescription is common among NVAF patients prescribed rivaroxaban. Increasing age and concurrent aspirin use are independent predictors of BE.

P469Minimally interrupted versus uninterrupted non-vitamin K anticoagulants for atrial fibrillation ablation. a meta-analysis of randomized controlled trials

Abstract Introduction More and more patients undergoing atrial fibrillation (AF) ablation are anticoagulated with direct oral anticoagulants (DOAC). In order to balance the peri-procedural risk of bleeding with the risk of stroke, an important clinical question is whether to continue an interrupted DOAC administration or minimal interrupt by skipping the last one or two doses before the procedure. Dealing with rare events, the randomized controlled trials (RCTs) looking at this question have not been sufficiently powered to give a definitive answer. Purpose To do a systematic review of the literature comparing an uninterrupted DOAC strategy to minimally interrupted (1-2 doses) strategy in the setting of AF ablation in terms of peri-procedural stroke and bleeding. Methods PubMed, EMBASE, and Cochrane databases were searched for RCTs comparing a strategy of uninterrupted versus minimally interrupted DOAC administration for atrial fibrillation ablation. The primary endpoint was a composite of clinically significant adverse events: ischemic stroke, transient ischemic attack (TIA), systemic embolism, and major or minor bleeding events. A random-effects meta-analysis was performed on the resulting trials. The systematic review protocol was pre-registered in the PROSPERO database. The study selection process followed the PRISMA statement. Results After checking and removing duplicates, 188 articles were screened by reading the title and abstract. 8 of them were selected for a full text screening. Because 3 were not randomized, finally, 5 RCTs met the inclusion criteria. A total of 1 769 patients were included in the meta-analysis, and the sample size of the individual RCTs ranged from 97 to 846 patients. The overall prevalence of paroxysmal AF varied from 54% to 100%. The mean age of patients ranged from 63,5 to 70 years, and 21,6% to 32,8% of the trial populations were women. Comorbidities, such as hypertension, dyslipidemia, and diabetes, were common. Most patients had CHA2DS2-VASc < 3; range from 1,7 to 2,7We found consistently low rates of strokes, TIAs, systemic embolisms and bleedings across all trials and both arms (RR = 0.98, 95% CI 0.69 – 1.38, I-squared = 0%, p = 0.874). Conclusion We found no evidence in favor of a difference between uninterrupted and interrupted administration of NOACs regarding the primary outcome of clinical thromboembolic and bleeding. Abstract Figure. Meta-analysis of the primary outcome

76Causes, safety and outcomes of switching from the Initial direct oral anticoagulant to another in patients with non-valvular atrial fibrillation from a single-center prospective study

Abstract Background Crossover between direct oral anticoagulants (DOACs) in real-life setting has been under investigated, with electronic registry-based study missing minor bleedings and minor ischemic events. The purpose of this study was to evaluate the switch from a DOAC to another DOAC, the reasons and the clinical events which happened after the switch. Methods Patients (pts) receiving first DOAC prescription at the Anticoagulation Center from February 2018 to September 2019 were consecutively included and followed. Causes of switch/dosage change as well as events or adverse events not leading to switch were registered. Results Overall, 300 pts were included, mean age 79.3 ± 8.5, male 53.7% (n = 161). 220 pts were received DOAC being naïve (70.7%), while 88 (29.3%) transitioned from vitamin K antagonists. Mean follow-up was 1.5 years from first DOAC prescription. Most prescribed DOACs was rivaroxaban (n = 107), followed by apixaban (n = 82), edoxaban (n = 59) and dabigatran (n = 52). No significant differences in age, gender, CHA2DS2VASc or HASBLED score was detected. Throughout follow-up, 61 patients (20.3%) needed changes in anticoagulation regimen. 24 patients changed DOAC dosage (8%), while 40 patients changed anticoagulants (13.3%), 39 switched from DOAC to another DOAC, 1 from DOAC to warfarin. Annual DOAC-to-DOAC switching rate was 15.0% (95%CI 10.8-20.3). Prevalence of switch varied across DOACs: 28.8% of pts taking dabigatran switched vs 11.0%, 10.2% and 9.3% of those taking apixaban, edoxaban and rivaroxaban respectively (p < 0.05). Apixaban was the most commonly preferred DOAC after switch, with 43% of pts receiving it after crossover. Causes of switch included minor bleeding (n = 15), major bleeding (n = 3), non-cardiovascular adverse events (n = 14), drug interaction or surgery (n = 4), renal function worsening (n = 2) and low compliance (n = 1). Comparative risk analysis revealed that prescription of dabigatran was associated with a 3-fold increase in risk of switching treatment (OR 3.59, 95%CI 2.09-6.19) compared to other DOACs. Apixaban, rivaroxaban and edoxaban seemed to have similar profile in terms of long-term adherence to treatment . Cox regression analysis, taking into account age, weight, CHA2DS2VASc and HASBLED scores, revealed significant differences in temporal distribution of crossover, with pts in dabigatran more likely to change treatment (HR 2.5, p < 0.05). After switching, 34 out of 39 pts remained free from cardiovascular events and non-cardiovascular adverse events. One pt had minor bleeding, only 1 had major (non-fatal) bleeding, and none reported compliance issues. Non-cardiovascular adverse events completely resolved after switch . Conclusion Minor bleeding and non cardiovascular adverse events are the most common causes of switch, which has a rate as high as 15% year. Crossover between DOACs seems safe, and might therefore be considered after minor bleeding and non-cardiovascular adverse events

Slightly elevated international normalized ratio predicts bleeding episodes in patients treated with direct oral anticoagulants

IntroductionPatients treated with direct oral anticoagulants (DOACs) are at increased bleeding risk. It is therefore of increasing interest to identify predictors of bleeding episodes to increase safety during treatment with DOACs.MethodsThis retrospective cohort study systematically reviewed medical records of 235 patients treated with either apixaban, rivaroxaban or dabigatran for non-valvular atrial fibrillation or venous thromboembolism and collected data on the international normalized ratio (INR) and all bleeding episodes.ResultsINR ≥ 1.5 was significantly associated with increased risk of minor and major bleeding events in patients treated with direct factor Xa inhibitors. This association was not present in patients treated with dabigatran. However, a high negative predictive value was identified for INR < 1.5 for all drugs. The relative risks of bleeding episodes in patients with INR ≥ 1.5 and INR < 1.5 were 5.1 and 0.20, respectively.ConclusionsOur results demonstrate a strong correlation between INR and risk of bleeding episodes during DOAC treatment. INR < 1.5 was a strong negative predictor for low bleeding risk independent of indication or choice of drug, and INR ≥ 1.5 was associated with increased risk of bleeding episodes in patients treated with direct factor Xa-inhibitors.

Real-world use of emicizumab in patients with haemophilia A: Bleeding outcomes and surgical procedures.

Emicizumab is a recombinant humanized bispecific antibody that bridges factor IXa and factor X to mimic the cofactor function of factor VIII. It is approved to prevent bleeding in patients with haemophilia A (HA). Outside of clinical trials, there is limited data on outcomes of patients treated with emicizumab, particularly in children without inhibitors. To report our experience treating patients with emicizumab, including (a) bleeding rates pre and postemicizumab, (b) peri-procedural management and outcomes and (c) serious drug-related adverse events. Multicentre observational study in patients with HA who started emicizumab prior to 15 May 2019. Data collection continued until 15 October 2019 and included demographics, disease history, bleeding events, invasive procedures, thrombotic events and death. Annualized bleeding rates (ABR) prior to emicizumab were compared to postemicizumab. Ninety-three patients (including three females)met inclusion criteria, 19 with an active inhibitor. Median age was 8.6years; patients <12years without inhibitors (n=49) accounted for the majority. ABR dropped from 4.4 (inhibitors) and 1.6 (non-inhibitors) to 0.4 (both groups) on emicizumab, P=.0012 and .0025, respectively. There were 28 minor (21 port removals) and two major procedures. Three patients received 1-2 doses of unplanned factor postoperatively to treat minor bleeding events. No patient discontinued therapy, and there were no thrombotic events or deaths. Our favourable clinical experience with emicizumab is similar to that reported in the clinical trials. Notably, this is the largest cohort of patients <12years without inhibitors treated with emicizumab.

Impact of bleeding events after percutaneous coronary intervention in patients on hemodialysis.

Coronary artery disease is common in patients on dialysis; there is a high rate of bleeding events after percutaneous coronary intervention (PCI) in such patients. We investigated the impact of bleeding events after PCI on mortality in patients on hemodialysis. We included 386 consecutive hemodialysis patients who underwent PCI using a drug-eluting stent (DES) between September 2004 and December 2017 in our hospital, and investigated the impact of bleeding events on all-cause mortality after PCI. Bleeding events were assessed by the Thrombolysis in Myocardial Infarction (TIMI) bleeding definition within 24months after PCI. A total of 42 patients experienced bleeding events. Of these, 30 patients (71.4%) had TIMI major bleeding events and 12 patients (28.6%) had TIMI minor bleeding events. Patients with bleeding events had significantly higher mortality than patients without bleeding events (survival rate, 55.1% vs 81.5%, log-rank: p < 0.001). These results suggest that bleeding events after PCI with a DES are notably associated with all-cause mortality among patients on hemodialysis. This is the first report about relationship between bleeding events and mortality to focus on patients on hemodialysis.

Periprocedural Direct Oral Anticoagulant Management: The RA-ACOD Prospective, Multicenter Real-World Registry.

Introduction There is scarce real-world experience regarding direct oral anticoagulants (DOACs) perioperative management. No study before has linked bridging therapy or DOAC-free time (pre-plus postoperative time without DOAC) with outcome. The aim of this study was to investigate real-world management and outcomes. Methods RA-ACOD is a prospective, observational, multicenter registry of adult patients on DOAC treatment requiring surgery. Primary outcomes were thrombotic and hemorrhagic complications. Follow-up was immediate postoperative (24–48 hours) and 30 days. Statistics were performed using a univariate and multivariate analysis. Data are presented as odds ratios (ORs [95% confidence interval]). Results From 26 Spanish hospitals, 901 patients were analyzed (53.5% major surgeries): 322 on apixaban, 304 on rivaroxaban, 267 on dabigatran, 8 on edoxaban. Fourteen (1.6%) patients suffered a thrombotic event, related to preoperative DOAC withdrawal (OR: 1.57 [1.03–2.4]) and DOAC-free time longer than 6 days (OR: 5.42 [1.18–26]). Minor bleeding events were described in 76 (8.4%) patients, with higher incidence for dabigatran (12.7%) versus other DOACs (6.6%). Major bleeding events occurred in 17 (1.9%) patients. Bridging therapy was used in 315 (35%) patients. It was associated with minor (OR: 2.57 [1.3–5.07]) and major (OR: 4.2 [1.4–12.3]) bleeding events, without decreasing thrombotic events. Conclusion This study offers real-world data on perioperative DOAC management and outcomes in a large prospective sample size to date with a high percentage of major surgery. Short-term preprocedural DOAC interruption depending on the drug, hemorrhagic risk, and renal function, without bridging therapy and a reduced DOAC-free time, seems the safest practice.

Safety and Feasibility of Home INR Monitoring for Outpatient Ventricular Assist Device Support in Children

The use of intracorporeal continuous flow (CF) ventricular assist devices- namely the Heartware™ HVAD™- has expanded dramatically in the children, with many being discharged home. We sought to evaluate the feasibility and outcomes of children discharged home with point of care (POC) INR monitors for their warfarin anticoagulation management. This is a retrospective single center review of all pediatric patients, aged ≤19 years at time of implantation, who were discharged home for longer than 1 week. Efficacy of warfarin anticoagulation and outcomes were evaluated in those with home POC monitors as compared to children who went to laboratory. Between November 11, 2012 and January 1, 2018, a total of 12 patients, 33% female, aged median 14.5 years (range 10-18 years), weighing median 65.8kg (range 18.0-89.5 kg) were discharged home or to rehab with HeartWare as a bridge to transplantation. Underlying diagnosis included dilated cardiomyopathy in 67% (n=8), arrhythmogenic right ventricular dysplasia (ARVD) in 8% (n=1), and biventricular congenital heart disease (CHD) in 25% (n=3).Two patients were discharged to rehab before returning home. All patients were discharged with Coagucheck XS™ POC INR machines, with goal INR of 2-3 in first 3 patients (23%) and goal INR of 2.5-3.5 in later 10 patients. There were a median number of INR tests of 27 (range 1-99) at home, over the course of a median 185 days (25-625) outpatient VAD support days. Overall median time in the therapeutic range(TTR) was 62.1%(range 20.0-70.7%). There was 100% adherence to clinician recommended INR testing at home. There was 4 bridging events with low molecular weight heparin for sub-therapeutic INR. There were no pump thrombosis or other thrombotic events. There were no major bleeding or clinically relevant non major bleeding events. Epistaxis was the most common minor bleeding event that was mitigated by dose reductions and preventative strategies. All patients were bridged to transplantation with no mortality. Use if home POC INR machines in children with intracorporeal VADs, in the outpatient setting was associated with 100% adherence to recommended testing regime. Despite low TTR, there was no major bleeding or thrombotic events.

83 Multicenter Evaluation of the Use of Nebulized Heparin for Inhalation Injury (HIHI2 Study)

Abstract Introduction Inhalation injury (IHI) causes significant morbidity and mortality secondary to local compromise of the respiratory system as well as systemic effects limiting perfusion and oxygenation. Nebulized heparin reduces fibrin cast formation and duration of mechanical ventilation in patients with IHI. To date, no study has compared both dosing strategies of 5,000 and 10,000 units to a matched control group. The objective of this study is to compare heparin 5,000 and 10,000 units to a historical control and determine which dosing strategy improves lung function and decreases mechanical ventilation duration. Methods This multicenter, retrospective, case-control study included adult patients with bronchoscopy-confirmed IHI. Each control patient, matched according to age and percent of total body surface area (TBSA), was matched to a patient who received 5,000 units and a patient who received 10,000 units of nebulized heparin, according to each institution’s inhalation injury protocol. Patients were excluded if they were pregnant, incarcerated, died within 72 hours of admission, terminally weaned for reasons other than burn or IHI, had a documented allergy to heparin or history of heparin-induced thrombocytopenia, history of pulmonary hemorrhage within 3 months, or history of a clinically important bleeding disorder. The primary endpoint of the study was total duration of mechanical ventilation (excluding patients who died or were not extubated). Secondary endpoints included 28-day mortality, ventilator-free days in the first 28 days, difference in lung injury scores, length of hospitalization, incidence of bronchoscopy, incidence of ventilator-associated pneumonia, and rate of bleeding events. Results Thirty-five matched patient trios met inclusion criteria. Groups were well-matched for age (p=0.975) and TBSA (p=0.855). When excluding patients who died or were never extubated, patients who received nebulized heparin, either 5,000 or 10,000 units, had 8–11 less days on the ventilator compared to controls (p=0.001). Mortality ranged from 3–14% overall, and no statistical difference was observed between groups. No major or minor bleeding events related to nebulized heparin were reported. Conclusions Mechanical ventilation days were significantly decreased in patients who received 5,000 or 10,000 units of nebulized heparin. There was no statistically significant difference in mortality between groups, supporting that either 5,000 units or 10,000 units of nebulized heparin should be used in IHI treatment. Applicability of Research to Practice To our knowledge, no previously published studies have simultaneously compared dosing strategies of 5,000 and 10,000 units to a control group. These results support the use of nebulized heparin for IHI to reduce the duration of mechanical ventilation.

3:36 PM Abstract No. 203 Safety and efficacy of percutaneous computed tomography–guided transplant pancreas biopsy

Percutaneous computed tomographic (CT)-guided biopsy is a minimally invasive alternative to open biopsy, not frequently described in the literature. The purpose is to describe and assess technique, complications, and diagnostic yield of CT-guided percutaneous transplant pancreas biopsy. This is a single institution retrospective review of 75 patients (47 women, 28 men, mean age 47) who underwent CT-guided transplant pancreas biopsy (n = 149) between April 2005 and October 2018.Three cases (2%) were aborted due to inadequate safe percutaneous approach. Biopsy results were classified based on final pathology as diagnostic (with the subcategory partially diagnostic used if the sample was adequate for the diagnosis of cell mediated rejection, but not humoral rejection) and nondiagnostic. Diagnostic yield and complication rates were evaluated. 149 percutaneous CT-guided biopsies of transplant pancreas were performed. 98% (n =143) of the biopsies used 17/18 Gauge coaxial core biopsy system, and 2% (n = 3) used a 19/20 Gauge coaxial device. On-site pathologic touch prep assessment was utilized for 91% of biopsies. Diagnostic tissue was obtained 94% of the time, of which 9% were considered partially diagnostic. 6% of the samples were deemed non-diagnostic. Of the diagnostic biopsies, 7 (51%) were positive for rejection (24% grade I, 16% grade II, 4% grade III, and 7% chronic) and 49% were negative for rejection. On-site pathologic touch prep did not appear to have an effect on sample adequacy (P = 0.9) nor did the number of cores (P =.28) or graft location (P = 1.0). The most common complication was minor bleeding (9%), pancreatitis (1%) and sedation related adverse events (1%); there was 1 moderate complication (hemorrhage requiring overnight observation), and no major complications. No significant difference in the INR (P = 0.68) or platelet count (P = 0.07) between patients who had bleeding complications and those who did not have bleeding complications. Image-guided percutaneous CT-guided transplant pancreas biopsies have high diagnostic yield with low complication rates.

Different unfractionated heparin doses for preventing arterial thrombosis in children undergoing cardiac catheterization.

The role of cardiac catheterization in pediatrics has progressed significantly over the last two decades, evolving from a primary diagnostic tool to a primary treatment modality in children with congenital heart disease. Vascular complications, particularly arterial thrombosis, are among the most common unwanted post-cardiac catheterization events. In 1974, unfractionated heparin proved to be superior to placebo in decreasing the incidence of arterial thrombosis in pediatric patients. However, the optimal dose of unfractionated heparin to be utilized in this setting remains a matter of controversy. This is an update of the review first published in 2014. To evaluate the use of low-dose (< 100 units/kg) versus high-dose (≥ 100 units/kg) unfractionated heparin administered as an intravenous bolus at the time of initiation of cardiac catheterization (that is, immediately after arterial puncture), with or without subsequent heparin maintenance doses, for the prevention of post-procedural arterial thrombosis in children. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 15 October 2019. We planned to undertake reference checking of identified trials to identify additional studies. No language restrictions were applied. We included randomized or quasi-randomized trials that compared low dose to high dose unfractionated heparin administered prior to cardiac catheterization. We selected studies conducted in children aged 0 to 18 years. The first screening of potentially eligible studies was conducted by one of the authors (MLA). The second screening, risk of bias assessment and data extraction were independently conducted by two authors (MLA, LRB). Outcomes (thrombotic events, bleeding complications, other complications) were treated as dichotomous variables. The effect measures used were risk ratio (RR), risk difference (RD) and number needed to treat (NNT), with 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. We identified no new studies for inclusion in this review. In total, two studies with a total of 492 participants were included. We had concerns about risk of bias for one of the two studies. The certainty of the evidence for our key outcomes was downgraded to moderate due to risk of bias concerns and imprecision. The confidence interval for the risk of arterial thrombotic events was compatible with benefits of either high or low unfractionated heparin dose regimens (RR low-dose versus high-dose 1.06, 95% CI 0.58 to 1.92). Only one of the studies reported the frequency of bleeding events and found no clear difference in the incidence of major or minor bleeding events between arms (RR low-dose versus high-dose 2.96, 95% CI 0.12 to 71.34 for major bleeding events; RR low-dose versus high-dose 1.38, 95% CI 0.46 to 4.13 for minor bleeding). This study also reported on the incidence of deep vein thrombosis when comparing the high versus low dose of heparin and reported a non-significant difference (RR low-dose versus high-dose 0.34, 95% CI 0.01 to 8.28). The other study lacked information about bleeding. Additional side effects of heparin other than bleeding events were not reported in either of the studies. Due to the limitations of the current evidence, small number of included studies, and lack of details reported in one study, we are unable to determine the effects of different dosing regimens of unfractionated heparin for the prevention of vascular thrombosis during cardiac catheterization in children. Further adequately powered, randomized clinical trials are needed.

Evaluation of the efficacy and safety of apixaban and rivaroxaban in cancer patients receiving concomitant active anti-neoplastic therapy at an outpatient cancer setting.

Venous thromboembolism is a common complication among cancer patients with an estimated risk of 20%. American Society of Clinical Oncology guidelines recommend direct oral anticoagulants for long-term anticoagulation but caution the use of direct oral anticoagulants because of drug-drug interactions with antineoplastic therapies. The clinical impact of these drug-drug interactions is yet to be studied in clinical trials. This study aims to evaluate the effect of the drug-drug interactions on venous thromboembolism recurrence and bleeding. This is a retrospective cohort study that included cancer patients with venous thromboembolism receiving apixaban or rivaroxaban with antineoplastic therapy. The impact of the drug-drug interaction was determined by its effect on the rates of venous thromboembolism recurrence and bleeding in patients with a drug-drug interaction compared to patients with no drug-drug interaction. The primary composite endpoint of venous thromboembolism recurrence and bleeding events occurred in 65% versus 62% of patients in drug-drug interaction and non-drug-drug interaction groups accordingly. There was a higher rate of venous thromboembolism recurrence and minor bleeding events with anti-mitotic microtubule inhibitors and a higher rate of minor bleeding events with hormonal therapy and alkylating agents. Among the drug-drug interaction group, there were no major bleeding events reported with mild drug-drug interactions when compared to moderate-to-severe drug-drug interactions. There was no difference in time to venous thromboembolism recurrence between rivaroxaban and apixaban. Due to small sample size, our study results could not confirm a higher risk of bleeding or venous thromboembolism recurrence with the drug-drug interactions. Further prospective study is warranted, but clinicians should be aware of these drug-drug interactions and identify them using available literature.

Safety of dabigatran etexilate for the secondary prevention of venous thromboembolism in children

AbstractThis open-label, single-arm, prospective cohort trial is the first phase 3 safety study to describe outcomes in children treated with dabigatran etexilate for secondary venous thromboembolism (VTE) prevention. Eligible children aged 12 to <18 years (age stratum 1), 2 to <12 years (stratum 2), and >3 months to <2 years (stratum 3) had an objectively confirmed diagnosis of VTE treated with standard of care (SOC) for ≥3 months, or had completed dabigatran or SOC treatment in the DIVERSITY trial (NCT01895777) and had an unresolved clinical thrombosis risk factor requiring further anticoagulation. Children received dabigatran for up to 12 months, or less if the identified VTE clinical risk factor resolved. Primary end points included VTE recurrence, bleeding events, and mortality at 6 and 12 months. Overall, 203 children received dabigatran, with median exposure being 36.3 weeks (range, 0-57 weeks); 171 of 203 (84.2%) and 32 of 203 (15.8%) took capsules and pellets, respectively. Overall, 2 of 203 children (1.0%) experienced on-treatment VTE recurrence, and 3 of 203 (1.5%) experienced major bleeding events, with 2 (1.0%) reporting clinically relevant nonmajor bleeding events, and 37 (18.2%) minor bleeding events. There were no on-treatment deaths. On-treatment postthrombotic syndrome was reported for 2 of 162 children (1.2%) who had deep vein thrombosis or central-line thrombosis as their most recent VTE. Pharmacokinetic/pharmacodynamic relationships of dabigatran were similar to those in adult VTE patients. In summary, dabigatran showed a favorable safety profile for secondary VTE prevention in children aged from >3 months to <18 years with persistent VTE risk factor(s). This trial was registered at www.clinicaltrials.gov as #NCT02197416.

Persistence, effectiveness and safety of dabigatran in "real-world" Chinese patients with nonvalvular atrial fibrillation.

The purpose of this study is to provide detailed data on treatment persistence and clinical outcomes in Chinese patients with nonvalvular atrial fibrillation (NVAF). A single-center retrospective observational study was conducted. A total of 26,663 NVAF patients were enrolled from January 1, 2014 to December 31, 2017, clinical information of whom were from inpatient and outpatients data system was collected. The 1-year treatment persistence rates of 11,350 dabigatran users were 24.5% in 2014, 36.6% in 2015, 37.7% in 2016 and 51.8% in 2017. The predominant reason of non-persistence patients was the cost of treatment. Incidence rates of all-cause death, ischemic stroke and embolism were 1.99/100 person-years, 2.56/100 person-years and 0.77/100 person-years, respectively. Incidence rates of minor bleeding events, intracranial hemorrhage and gastrointestinal hemorrhage were 10.05/100 person-years, 0.51/100 person-years and 0.85/100 person-years, respectively. In conclusion, it is of importance for Chinese clinicians to know about these information because dabigatran is a relatively new drug in China. Compared with other reported data, patients of this study have (1) lower dabigatran persistence and lower incident rates of all-cause death, systemic embolism, minor bleeding events and gastrointestinal hemorrhage and (2) higher incident rates of ischemic stroke and intracranial hemorrhage.

Light anti-thrombotic regimen for prevention of device thrombosis and/or thrombotic complications after interatrial shunts device-based closure

AimsThe optimal antiplatelet therapy after atrial septal defect (ASD) or patent foramen ovale device closure (PFO) remain to be established. We evaluated the safety and effectiveness of 6-month 100 mg Aspirin (ASA) regimen in the very long-term follow up after intracardiac echocardiography (ICE) –aided interatrial shunt closure in a large retrospective cohort. MethodsSingle-center retrospective analysis which included medical and instrumental data of 789 consecutive patients referred to our institution over a 15 years period due interatrial shunt catheter-based closure. ResultsFinally, 734 patients were included in the analysis (mean age 46.1 ± 14.6 years, 398 females): ASD and PFO closure were successfully performed in 281 and 453 patients, respectively. Over the follow-up period, no major bleeding events were observed while the rate of minor bleeding events was 0.9%. Tolerance problems were detected in 3.4% of cases (n==28). In 11 patients (1.5%) an abnormal complete blood count was detected and monitored up to normalization. On a mean follow –up of 10.3 ± 3.0 years (range 1–15), 10 patients (1.36%) had a persistent moderate shunt 12 months after closure and maintained Aspirin 100 mg life-long, whereas the remaining 724 suspended the treatment after 6 months. Device thrombosis in ASD and PFO groups were 0% and 0.2%, respectively. A cerebral ischemic event occurred in 0.4% of the entire cohort. ConclusionsA regimen of 100 mg of ASA for six months after ASD/PFO closure appeared to be both safe and effective in preventing device thrombosis and major bleedings.

Safety and Efficacy of Direct Oral Anticoagulant Therapy in Patients With Cancer

Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with malignancy. The currently available guidelines have shown greater support for utilization of low-molecular-weight heparin (LMWH) over direct oral anticoagulants (DOACs) in cancer-associated VTE. Current data on the safety and efficacy of DOAC therapy in patients with cancer are lacking. Objective: To evaluate the safety and efficacy of the use of DOACs compared to LMWH in patients with cancer. Methods: A retrospective review of outpatient records was completed to identify patients with documented cancer diagnosis and either a DOAC or LMWH as a listed medication. Patients were excluded if they had atrial fibrillation, valvular disease, antiphospholipid antibody syndrome, current pregnancy, body mass index (BMI) >40 kg/m2 or weight >120 kg, severe renal or hepatic impairment, or were on concomitant therapy with a significant interacting medication. The primary outcome was frequency of VTE recurrence, and secondary outcomes included the frequency of major and minor bleeding and other thrombotic events. Results: One hundred fifty-six patients were included in the study population, 78 in both the DOAC and LMWH groups. Venous thromboembolism recurrence occurred in 5 (6.4%) patients in the DOAC group and 8 (10.3%) patients in the LMWH group (P = .39). There was no significant difference in major or minor bleeding or other thrombotic events between the 2 groups. Conclusion: The frequency of VTE recurrence was similar between DOACs and LMWH in patients with cancer. DOACs may be an alternative agent to LMWH for the prevention of recurrent VTE in patients with cancer.

Nursing Care Practices for Patients With Pulmonary Embolism Undergoing Treatment With Ultrasound-Assisted Thrombolysis: An Integrative Review.

Pulmonary embolism (PE) remains a common and life-threatening event. The use of ultrasound-assisted thrombolysis (USAT) for the delivery of thrombolytic agents to the clot has developed in the last 10 years. A search yielded no evidence-based practice guidelines for the nursing care of the patient with PE during and post USAT treatment and specifically when using the EKOS machine. The objective of this integrative review was to explore the literature and web for any information on the use of USAT for adults with PE both during and post treatment. Our goal was to examine nurse-specific practices to develop appropriate protocols. We conducted a search of PubMed, Web of Science, EBSCOhost, CINAHL, Google Scholar, and Google for any guidelines, observational studies, or experimental studies using USAT for PE in adults. Nurse authors independently reviewed the articles using a standardized data coding form. Information abstracted included sample and setting characteristics, access characteristics, medication, sheath removal, compression, and bleeding events. Twenty-two articles, published in 2008-2019, met the eligibility criteria. Most studies were small retrospective studies at single sites. Variation existed on the clinician, the clinical area for placement, the amount and duration of delivery of medication, and where care was provided during the infusion. Few studies noted sheath removal or compression procedures. Fifteen studies reported 1 fatal, 12 major, 4 moderate, and 36 minor bleeding events at the catheter insertion sites. There is lack of sufficient information for the development of nursing practice guidelines for this new technology.

Is there a cardiovascular protective effect of aspirin in chronic kidney disease patients? A systematic review and meta-analysis.

To perform a systematic review and meta-analysis to evaluate the cardiovascular prevention effect of aspirin among patients with chronic kidney disease (CKD). A comprehensive literature search was conducted in Embase, PubMed, and Cochrane library (up to March 2019) without language limitations. Randomized control trials (RCT) and observational studies that met the inclusion and exclusion criteria were included. Two reviewers independently extracted data, and evaluated study quality using modified Jadad score for RCTs and Newcastle-Ottawa Scale for observational study. A meta-analysis was conducted in the Stata 15.0 software using the DerSimonian and Laird random-effects model. 1768 references were identified from literature searching. Four RCTs and four cohort studies that reported the cardiovascular prevention outcome of aspirin in CKD patients (38,341 participants) were included in this review. The pooled data revealed that aspirin had no significant prevention effect on cardiovascular events among CKD patients (RR = 0.96, 95% CI, 0.59-1.13). There was also no significant reduction in cardiovascular mortality and all-cause mortality. Although we found no significant increased risk in major bleeding events, there was a statistically significant increased risk of minor bleeding events (RR = 2.57, 95% CI, 1.60-4.13) and renal events (RR = 1.30, 95% CI, 1.02-1.65) for aspirin use. Our review indicated that aspirin use in CKD patients had no prevention effect on cardiovascular events and no statistically significant reduction in risk of cardiovascular or all-cause mortality, with a significant increased risk of minor bleeding and renal events.

Post-treatment Antiplatelet Therapy Reduces Risk for Delayed Cerebral Ischemia due to Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) has a strong impact on outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). Positive effect of antiplatelet therapy on DCI rates has been supposed upon smaller SAH series. To analyze the benefit/risk profile of antiplatelet use in SAH patients. This retrospective case-control study was based on institutional observational cohort with 994 SAH patients treated between January 2003 and June 2016. The individuals with postcoiling antiplatelet therapy (aspirin with/without clopidogrel) were compared to a control group without antiplatelet therapy. Occurrence of DCI, major/minor bleeding events in the follow-up computed tomography scans, and favorable outcome at 6 mo after SAH (modified Rankin scale<3) were compared in both groups. Of 580 patients in the final analysis, 329 patients received post-treatment antiplatelet medication. There were no significant differences between the compared groups with regard to basic outcome confounders. Aspirin use was independently associated with reduced DCI risk (P<.001, adjusted odds ratio=0.41, 95% confidence interval 0.24-0.65) and favorable outcome (P=.02, adjusted odds ratio=1.78, 95% confidence interval 1.06-2.98). Regarding bleeding complications, aspirin was associated only with minor bleeding events (P=.02 vs P=.51 for major bleeding events). Regular administration of aspirin might have a positive impact on DCI risk and outcome of SAH patients, without increasing the risk for clinically relevant bleeding events. In our SAH cohort, dual antiplatelet therapy showed no additional benefit on DCI risk, but increased the likelihood of major bleeding events.