Bleeding Criteria Research Articles

Anticoagulation for Distal Lower-extremity Deep Venous Thromboses.

Deep venous thrombosis (DVT) has an incidence of 45 to 117 per 100,000 person-years.1 Distal DVT, defined as a venous thrombosis isolated to the calf veins, comprises one-third to one-half of all DVTs.2 However, the treatment of distal DVTs is more controversial with significant variations in practice with regard to decisions on anticoagulation.3.

Prevalence of the Academic Research Consortium for High Bleeding Risk Criteria and Prognostic Value of a Simplified Definition.

The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria have been suggested as the standard definition of HBR. However, the prevalence of individual criteria and their prognostic value for long-term bleeding events after percutaneous coronary intervention are scarcely studied. The study population comprised 1,193 patients treated with everolimus-eluting stents between 2010 and 2011. Data on all 17 major and minor criteria of the ARC-HBR definition were retrospectively collected, and applied to this study population. Major bleeding was defined as the occurrence of a BARC type 3 or 5 bleeding event. A simplified definition was developed by excluding the low-frequency criterion, and the prognostic value was assessed by a receiver-operating characteristic curve. Mean follow-up was 2,996±433 days and there were 656 HBR patients (55.0%). The cumulative incidence of major bleeding was significantly higher in the HBR group than in the non-HBR group (16.2% vs. 5.7% at 8 years, P<0.001). The frequencies of 6 of the 17 criteria were less than 1%. The prognostic value of the simplified definition made by excluding these 6 criteria for major bleeding was comparable to that of the original (c-statistic=0.598 and 0.600, P=0.08). Some risk criteria of the ARC-HBR definition are observed infrequently. Our simplified definition identified patients with long-term bleeding risk as successfully as the original definition.

Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study establishing diagnostic criteria and prognostic importance

BackgroundWe aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. MethodsThis was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. ResultsOf 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin <70 g L−1, transfusion of ≥1 unit of red blood cells, or that was judged to be the cause of death. Bleeding independently associated with mortality after noncardiac surgery occurred in 17.3% of patients (2782). Death occurred in 5.8% of patients with BIMS (161/2782), 1.3% (39/3028) who met bleeding screening criteria but not BIMS criteria, and 1.1% (115/10 269) without bleeding. BIMS was associated with mortality (adjusted hazard ratio: 1.87; 95% confidence interval: 1.42–2.47). We estimated the proportion of 30-day postoperative deaths potentially attributable to BIMS to be 20.1–31.9%. ConclusionsBleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin <70 g L−1, blood transfusion, or that is judged to be the cause of death, is common and may account for a quarter of deaths after noncardiac surgery. Clinical trial registrationNCT00512109.

Preoperative prediction of Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study

BackgroundDiagnostic criteria for Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS) have been defined as bleeding that leads to a postoperative haemoglobin <70 g L−1, leads to blood transfusion, or is judged to be the direct cause of death. Preoperative prediction guides for BIMS can facilitate informed consent and planning of perioperative care. MethodsIn a prospective cohort study of 16 079 participants aged ≥45 yr having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011, 17.3% (2782) experienced BIMS. An electronic risk calculator for BIMS was developed and internally validated by logistic regression with bootstrapping, and further simplified to a risk index. Decision curve analysis assessed the potential utility of each prediction guide compared with a strategy of identifying risk of BIMS based on preoperative haemoglobin <120 g L−1. ResultsWith information about the type of surgery, preoperative haemoglobin, age, sex, functional status, kidney function, history of high-risk coronary artery disease, and active cancer, the risk calculator accurately predicted BIMS (bias-corrected C-statistic, 0.84; 95% confidence interval, 0.837–0.852). A simplified index based on preoperative haemoglobin <120 g L−1, open surgery, and high-risk surgery also predicted BIMS, but less accurately (C-statistic, 0.787; 95% confidence interval, 0.779–0.796). Both prediction guides could improve decision making compared with knowledge of haemoglobin <120 g L−1 alone. ConclusionsBIMS, defined as bleeding that leads to a postoperative haemoglobin <70 g L−1, leads to blood transfusion, or that is judged to be the direct cause of death, can be predicted by a simple risk index before surgery. Clinical trial registrationNCT00512109.

Safety and efficacy of anticoagulant monotherapy in atrial fibrillation and stable coronary artery disease: A systematic review and meta-analysis

BackgroundAdjunctive use of oral anticoagulant (OAC) and antiplatelet therapy (APT) in patients with stable coronary artery disease (CAD) and nonvalvular atrial fibrillation (AF) is a challenge of daily practice. MethodsA comprehensive literature search of databases was performed to identify studies comparing the safety and efficacy of OAC monotherapy and combined therapy (OAC plus single (S) APT). Events including major adverse cardiovascular events (MACE), all-cause mortality, stroke and major bleeding were analyzed. ResultsSeven articles comprising 11,070 subjects were identified. Combined therapy was associated with a significantly higher risk of major bleeding (pooled hazard ratio (HR) of 1.62, 95% CI 1.40–1.86, p=<0.0001) compared to the OAC monotherapy. There was no significant difference between the two comparison arms in terms of MACE (HR 1.14; 95% CI 0.97–1.34, p = 0.11), stroke (HR 1.05; 95% CI 0.77–1.43, p = 0.78) and all-cause mortality (HR 1.15; 95% CI 0.94–1.40, p = 0.16). Stratified analysis by inclusion of only patients with coronary stents attenuated the safety effect of monotherapy. Subgroup analysis based on the study design, type of OAC, major bleeding criteria and APT revealed findings consistent with the pooled HR. The combined therapy group had a 19% and 38% higher risk of MACE in studies with a history of MI (p = 0.03) and with the use of rivaroxaban (p = 0.02), respectively. ConclusionOAC monotherapy might have a lower incidence of major bleeding events with no higher overall risk of MACE, ischemic stroke and all-cause mortality compared to the combined therapy group.

Bleeding assessment and bleeding severity in thrombocytopenic patients undergoing invasive procedures.

Bleeding assessment and bleeding severity in thrombocytopenic patients undergoing invasive procedures.

Study of spectrum of endometrial pathology in patients with abnormal uterine bleeding and its clinicopathological correlation

Background: The term abnormal uterine bleeding (AUB) is defined as any bleeding from uterus not fulfilling the criteria of normal uterine bleeding in terms of frequency, duration and amount. AUB is one of the most common complaints in gynaecological OPDs resulting in endometrial sampling. Material and methods: The present study was conducted in SHKM Government Medical College Nalhar, Nuh, Haryana from January 2018 to November 2019 by Departments of Pathology and Gynaecology. One hundred eighty cases of AUB were included in the study. Endometrial samples such as endometrial biopsy, dilatation and curettage material (D&C), fractional curettage specimens and hysterectomy specimens were included in the study. Gross and microscopic features were studied. Results: The age group of patients in this study ranged from 20 to 67 years. Maximum numbers of cases (n=90) were in the age group of 40 to 49 years. Most common presenting complaint was menorrhagia (50.5%). Normal cyclical endometrium was found to be the commonest histopathological pattern with proliferative endometrium in 48.8% and secretory endometrium in 22.2% cases. On histopathology rest of the cases revealed disordered proliferative phase in 20(11.1%) cases, endometrial hyperplasia in 2(1.1%), chronic endometritis in 8(4.4%), granulomatous inflammation in 2(0.01%), senile cystic atrophy in 6(3.3%) and malignancy in 4(2.2%) cases. Conclusion: Disordered proliferative phase endometrium, hyperplasia and carcinoma endometrium are seen more commonly in perimenopausal and postmenopausal females. Hence, histopathological 3 examination should be considered mandatory in women above 40 years of age presenting with AUB to rule out any malignant pathology.

Efficacy and Safety of Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism

Background: Obesity is a well-known risk factor for venous thromboembolism (VTE), however, obese patients are under-represented in clinical trials (1;2). Four direct oral anticoagulants (DOACs) have been approved for the treatment of acute VTE (3-6), including the direct Factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the direct thrombin inhibitor, dabigatran. Given the lack of data in this population, it is unclear if DOACs can be used safely. Objectives: To evaluate the efficacy and safety of DOACs for the treatment of VTE in obese patients. Methods: We conducted a retrospective, single-centre cohort study in London (Canada) to compare the efficacy and safety of DOACs for the treatment of acute VTE in obese patients. We screened electronic and hard copy charts of adult patients referred to our thrombosis clinic for treatment of an objectively confirmed acute VTE between January 2012 and December 2017. Patients treated with DOACs or Warfarin were selected and followed from diagnosis of the index event until cessation of anticoagulation or up to 1 year. Our study population was analyzed by BMI (BMI ≥ 30 kg/m2versus &amp;lt; 30 kg/m2) and body weight (≥120 kg vs. &amp;lt;120 kg). Patients were excluded if they were on anticoagulation therapy for conditions other than VTE (e.g; atrial fibrillation), cancer-associated thrombosis, or missing data. The primary outcome measure was VTE recurrence during the anticoagulation treatment period and was defined according to the ISTH criteria (7). Our secondary outcome was the occurrence of bleeding events A bleeding event is defined as: a) Major Bleeding: bleed resulting in a hemoglobin drop of &amp;gt; 20 g/L, clinically overt and requiring more than 2 units of packed red blood cells, a hemorrhage requiring permanent cessation of anticoagulation and any retroperitoneal or intracranial hemorrhage; b) Minor Bleeding: bleed with no or little clinical significance, associated with no cost and does not require medical evaluation; and c) clinically significant non-major bleeding: does not fulfill criteria for major or minor bleeding but requires patients to be seek medical attention and/or minor procedures (8). Groups were compared using Chi-square or Fisher's exact test for categorical variables, as appropriate. The significance level was set at 0.05. Risk ratios (RR) and 95% confidence intervals (95% CI) for VTE recurrence and bleeding among DOAC groups and patients treated with Warfarin were analyzed by logistic regression. All statistical analyses were conducted using IBM SPSS Statistics version 25 (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). Results: Of 1143 potentially eligible patients, 777 fulfilled our inclusion criteria: 278 (35.8%) obese patients treated with DOACs, 266 (34.2%) non-obese patients on DOACS and 233 (30%) obese patients on Warfarin. Of the patients on DOACs, 80% (n= 436) were on rivaroxaban, while the remaining 20% were either on apixaban or edoxaban (n= 108). Among patients on DOACs VTE recurrence was observed in 2.1% (N=6) of patients with BMI ≥ 30 kg/m2 and 2.8% (N=2) of patients with 120 kg or more, with no differences in the risk of VTE recurrence (Table 1). The proportion of major bleeding events for patients on DOACs was 1.1% (N=3) for patients with BMI ≥ 30 kg/m2 and 1.4% (N=1) for patients with 120kg or more. There were no significant differences with respect to major and total bleeding risk (Table1). When comparing obese patients on DOACs vs Warfarin we did not find differences in the risk of VTE recurrence among patients with a BMI ≥ 30 kg/m2 [RR 2.59 95% IC (0.51-12.96), p= 0. 247] or body weight ≥120 kg [RR 4.33 95% IC (0.21-89.43), p= 0. 337] (Table 2). Among obese patients those treated with DOACs had a similar proportion and risk of total bleeding and major bleeding events compared to those on warfarin (Table 2). Conclusions: Our retrospective study suggests that DOACs at standard doses appear to have similar efficacy and safety in obese patients as defined herein. However, since most of our patients were treated with rivaroxaban, information on other agents is inconclusive. Information on patients with extreme body weight was limited. Disclosures Louzada: Bayer: Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

Direct Oral Anticoagulants Compared to Low Molecular Weight Heparin in the Treatment of Cancer-Associated Thromboembolism: An Updated Meta-Analysis of Randomized Controlled Trails

Introduction: Cancer patients have approximately 4 times higher risk of developing venous thromboembolism (VTE) compared to the general population. High tendency of bleeding from anticoagulant use in this population makes the treatment of cancer-associated thromboembolism (CAT) very challenging. Low molecular weight heparin (LMWH) is still considered as standard treatment for CAT. Direct oral anticoagulants (DOAC) have emerged as a potential alternative for LMWH due to the ease of administration and predictable pharmacokinetics, but data on DOACs in CAT is limited. Few randomized controlled trials (RCT) published recently have compared the efficacy and safety of DOACs with LMWH in the treatment of CAT. Hence, we conducted an updated meta-analysis of RCTs to determine the relative risk of recurrent VTE and bleeding complications associated with DOACs compared to LMWH in the treatment of thromboembolism in patients with cancer, and to evaluate if the risk estimates have changed since prior report (Li et al.). Methods: We performed a systemic search using Embase, Medline, and the meeting abstracts with appropriate keywords through 06/30/19, to find all RCTs comparing a DOAC with LMWH in treatment of patients with CAT. The search strategy, study selection, data extraction and analysis were performed in accordance with the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines. We pooled the point estimates in form of risk ratios (RR) with respective 95% confidence intervals (CI), using the random effects model (Mantel-Haenszel method) of Der Simonian and Laird. Heterogeneity of effect size across studies was quantified using I2 statistic and Cochran's Q. Publication bias was assessed by the Egger's regression test. All the statistical analyses were performed with the RevMan 5.3 software. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2014. Results: Overall a total of 1,739 patients with CAT (870 in the DOAC arms and 869 in LMWH arms) from three RCTs were included in the final analysis. Characteristics of studies included in the analysis are summarized in table 1. Different DOACs (Select-D: rivaroxaban, Hokusai VTE cancer: edoxaban and ADAM VTE: apixaban) were used to compare with dalteparin in included trials. Duration of anticoagulation was 6 to 12 months in these studies. Use of DOAC was associated with a significantly lower risk of recurrent VTE in comparison with LMWH [pooled RR 0.48, 95%CI: 0.26-0.87, p = 0.02, I2 = 56%, figure 1]. In addition, there was no statistically significant increase in the risk of major bleeding in patients on the DOAC arms, as compared to those on LMWH arms [ pooled RR 1.55 ,95%CI: 0.79-3.04, p = 0.20, I2 = 29%, figure 2]. Criteria for major bleeding in the studies were defined by the International Society on Thrombosis and Hemostasis. The pooled RR for clinically relevant non major bleeding (CRNMB) was 1.80 [95%CI: 0.96-3.38, p = 0.07, I2 = 60%, figure 3], thus suggesting no significant difference in risk of CRNMB between DOAC and LMWH groups. Moderate heterogeneity was noted across trials. We found no publication bias among studies included in the analysis. Conclusion: In our meta-analysis, use of DOACs for the treatment of CAT was associated with a significantly decreased risk of recurrent VTE compared to LMWH. There was no significant difference in the incidence of major or non-major bleeding events between DOAC and LMWH groups. These study results provide additional evidence for potential use of DOAC as a safe and effective alternative to LMWH for the treatment of thromboembolism in patients with cancer. Disclosures No relevant conflicts of interest to declare.

Hematoma Risk After Needle Electromyography in Patients Using Newer Oral Anticoagulants.

To assess the safety of needle electromyography in patients on non-vitamin K oral anticoagulants (NOACs) compared with warfarin. A retrospective chart review was done in patients who underwent needle electromyography studies while they were using warfarin and NOACs. After the needle electromyography, all the patients were monitored for 2 hours and ultrasound of high-risk muscle groups was done. The complications were classified based on the International Society on Thrombosis and Hemostasis definitions. Fifty-eight patients were included: 29 were using NOACs and the other 29 were on warfarin. The mean age was 59.33 ± 16 years. Hemorrhagic complications from needle electromyography were noted in 9 patients: 7 (77.7%) NOACs and 2 (22.3%) warfarin. Among them, 6 patients (66.6%) met the diagnostic criteria for Clinically Relevant Non-Major Bleeding criteria proposed by International Society on Thrombosis and Hemostasis and 3 patients (33.4%) had an asymptomatic hematoma on ultrasound evaluation. A total of 267 muscles were tested and only 9 (3.3%) muscles had hemorrhagic complications. One patient (rivaroxaban) had acute bleeding requiring pressure bandage, five patients (two apixaban, two rivaroxaban, and one warfarin) had clinical hematoma that required ice packs, and three patients (two rivaroxaban and one warfarin) had a hematoma on ultrasound of deep muscles. Patients on NOACs had minimal risk of clinically relevant hemorrhagic complications, and the risk is not significantly different from those on warfarin.

P4619Comparison of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding risk scores for predicting in-hospital bleeding in acute myocardial infarction patients undergoing primary PCI

Abstract Background Considering clinical importance of bleeding complications in patients with acute myocardial infarction (AMI), bleeding risk stratification is a key part of the management of these patients. CRUSADE, ACTION and ACUITY-HORIZONS bleeding risk scores are available for predicting in-hospital major bleeding events in patients with acute myocardial infarction. Purpose We aimed to evaluate performance of the three above mentioned risk scores for predicting in-hospital bleeding events defined according to The Bleeding Academic Research Consortium (BARC) criteria. Methods From a prospective electronic registry of a high-volume catheterization laboratory in a period from January 2009 to December 2017, a total of 6505 consecutive patients with acute myocardial infarction who underwent pPCI were included in analysis. Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow (H-L) goodness-of-fit test and C-statistic, respectively. Results Overall there were 372 (5.7%) bleeding events out of which 117 (1.8%) fulfilled stage BARC 3 or higher bleeding criteria. All three scores showed good model calibration as assessed by the H-Ls test and very good discriminative power for BARC 3 of higher bleeding events detection as assessed by C-statistics (Table 1 &amp; Figure 1): Bleeding events stage BARC 3 or higher were statistically highly related with higher in-hospital mortality (13.7% vs. 3.5%; p&lt;0.000). Table 1 Risk score H-L H-L p AUC 95% CI p CRUSADE 11.46 0.177 0.761 0.750–0.771 vs. ACUITY = ns vs. ACTION &lt;0.000 ACUITY-HORIZONS 10.47 0.236 0735 0.724–0.745 vs. ACTION = ns ACTION 5.74 0.677 0.701 0.698–0.712 Figure 1 Conclusions All three evaluated scores showed very good discriminative capacity for predicting BARC 3 or higher bleeding events in patients undergoing pPCI for AMI.

579 The Efficacy and Safety of Andexanet Alfa in Patients With Acute Gastrointestinal Bleeding While Taking Factor Xa Inhibitors: An ANNEXA-4 Sub-Analysis

INTRODUCTION: Andexanet alfa is a recombinant modified human Factor Xa (FXa) decoy protein developed to reverse the anticoagulant effect of FXa inhibitors. METHODS: ANNEXA-4 was a prospective single-arm study of andexanet alfa in patients with acute major bleeding while taking a FXa inhibitor. Patients with major gastrointestinal (GI) bleeding were eligible if they had (1) signs/symptoms of hemodynamic compromise or (2) bleeding associated with a hemoglobin (Hb) drop ≥2 g/dL or baseline Hb ≤8 g/dL. Upon enrollment, patients were treated with one of two andexanet dosing regimens based on the type, timing, and dose of the most recent inhibitor intake. Efficacy was evaluated in all patients who met the bleeding criteria above and had a baseline anti-FXa activity ≥75 ng/mL (≥0.25 IU/mL for enoxaparin). Co-primary endpoints were the change in anti-FXa activity and the achievement of hemostasis, as adjudicated by an independent committee, at 12 hours after andexanet treatment. Hemostasis was defined as: excellent if the red blood cell transfusion-corrected Hb at 12 hours was ≤10% lower than baseline, good if Hb was 10-20% lower, and poor/none if Hb was &gt;20% lower. RESULTS: Of 352 patients enrolled in the study, 90 had GI bleeding, of whom 62 were included in the efficacy analysis. Median age was 76 years (range 24-95); 51 (57%) were male. Patients were receiving rivaroxaban (n = 44), apixaban (n = 5), and edoxaban (n = 3) at study entry. Bleeding location was identified in 48 patients (upper n=27, lower n = 21) and unknown in 42 patients. 66 (73%) patients had some evidence of hemodynamic compromise, including 38 (42%) patients with hypotension. Mean Hb at the time of dosing was 4.9 ± 1.4 g/dL. In patients taking rivaroxaban, the baseline anti-FXa activity was 267 ± 168.5 ng/mL and the percent reduction with andexanet was 94% (95%CI 89-96). In apixaban patients, the baseline anti-FXa activity was 244 ± 215.0 ng/mL and the percent reduction with andexanet was 92% (95%CI 88-95). Excellent/good hemostasis was achieved in 85% of evaluable patients. 58 (94%) of 62 patients received red blood cell transfusions, 3 (5%) received platelet transfusion, and 2 (3%) received a coagulation factor product. 30-day rates of thrombosis and death were 6% and 13%, respectively. CONCLUSION: In patients with major GI bleeding treated with andexanet, a high rate of effective hemostasis was achieved. The thrombosis and mortality rates are consistent with prior studies in this patient population.

Tatalaksana Praktis Gangguan Haid di Praktek Sehari-hari

Menstrual disorders are the most common disorders in women of childbearing age and the most common complaint in gynecological outpatient practices in several hospitals. Besides disrupting activities, menstrual disorders can be a serious problem as a life threatening condition. Menstrual disorders can be divided based on the duration and the etiology. Based on the duration of occurrence, acute and chronic can be distinguished. Etiology can be distinguished based on abnormal uterine bleeding criteria (PALM-COEIN). The management of this kind of disorder depends on the type of cause of abnormal uterine bleeding. Surgical and non-surgical management can be used as an option in the treatment of menstrual disorders. Hormonal therapy options are the most popular treatment options at present with minimal side effects and relatively affordable prices. Management of abnormal uterine bleeding aims to improve the general condition, stop bleeding, and restore the function of reproductive hormones. Stopping bleeding can be done with medical, dilatation and curettage, as well as operative measures.

Healthcare resource utilization and costs among patients with direct oral anticoagulant or warfarin-related major bleeding

IntroductionDirect oral anticoagulants (DOACs) have expanded the options for antithrombotic therapy. DOAC-related major bleeds are associated with favorable outcomes compared to warfarin in clinical trials and routine practice. However, it is unclear whether management of DOAC-associated major bleeding incurs higher resource utilization and costs. Materials and methodsWe screened medical records of patients ≥ 66 years with atrial fibrillation admitted to one of five tertiary care hospitals in Ontario, Canada with a hemorrhage. We abstracted bleeds involving DOACs or warfarin and linked them to administrative databases to capture length of hospital stay, blood product use, procedural interventions, intensive care unit (ICU) utilization and related direct medical costs. To control for confounders, multivariate logistic and linear regressions were used for binary and linear outcomes respectively. ResultsAmong 19,061 records screened, 1978 (10.4%) cases involving 1632 patients met criteria of oral anticoagulant-associated bleeding. Baseline characteristics between DOAC and warfarin groups were similar. Blood product costs were higher for DOACs (all comparisons DOACs vs. warfarin, $1456 vs. $1109, mean difference $347, 95% CI $185 to $509), but length of stay and ICU use were similar. Mean direct medical costs did not differ ($9217 vs. $10,790, adjusted relative ratio 0.94, 95% CI 0.84–1.05). ConclusionsPrior to introduction of DOAC-specific reversal agents, resource utilization and medical costs were comparable between DOAC- and warfarin-associated major bleeds, despite marginally higher blood product costs incurred by the former. Resource intensity associated with anticoagulant-related bleeding remains high, and our data provide measures for cost-effectiveness evaluation of emerging DOAC antidotes.

Criteria for Clinically Relevant Bleeding in Critically Ill Children: An International Survey.

Bleeding, a feared complication of critical illness, is frequent in critically ill children. However, the concept of clinically relevant bleeding is ill-defined in this population. There are many established diagnostic criteria for bleeding, but only one estimates bleeding in critically ill adults, and none exist for critically ill children. Our objective was to identify the factors that influence pediatric intensivists' perception of clinically relevant bleeding. Self-administered, web-based survey with 9-point Likert scales, to qualify the clinical significance of 103 bleeding characteristics in critically ill children. Online survey. Pediatric critical care physicians and nurse practitioners. None. The response rate was 40%, with 225 respondents from 16 countries. Characteristics most frequently identified as clinically relevant were bleeding in critical locations (e.g., pericardium, pleural space, CNS, and lungs); requiring interventions; leading to physiologic repercussions, including organ failure; and of prolonged duration. Quantifiable bleeding greater than 5 mL/kg/hr for more than 1 hour was frequently considered clinically relevant. Respondents identified the following characteristics as clinically irrelevant: dressings required to be changed no less frequently than every 6 hours, streaks of blood in gastric tubes, streaks of blood in endotracheal tubes or blood in endotracheal tubes only during suctioning, lightly blood-tinged urine, quantifiable bleeding less than 1 mL/kg/hr, and noncoalescing petechiae. Perception of the clinical relevance of bleeding was not associated with the respondent's geographical location of clinical practice or years of experience. This international survey provides a better understanding of the factors that influence the pediatric intensivists' assessment of the clinical relevance of bleeding in critically ill children. It provides the foundation for the development of a validated, diagnostic definition of clinically relevant bleeding in this population.

Retrospective cohort study of 4,591 dental implants: Analysis of risk indicators for bone loss and prevalence of peri-implant mucositis and peri-implantitis.

BackgroundDue to the risk of peri‐implantitis, following dental implant placement, this study aimed to evaluate risk indicators associated with marginal bone loss from a retrospective open cohort study of 4,591 dental implants, placed in private practice, with 5‐ to 10‐year follow‐up. Furthermore, the prevalence of mucositis and peri‐implantitis among the study cohort was evaluated, comparing strict versus relaxed criteria for bleeding on probing.MethodsPeriapical radiographs were used to evaluate changes in crestal bone level. Peri‐implant soft tissue was evaluated using an ordinal mucosal index in comparison with the conventional binary threshold for bleeding (i.e., present or not). Periodontal probing depth was not evaluated. Linear mixed models were used to evaluate bone level over time, and other risk indicators, at the patient and implant level.ResultsRisk indicators found to have a significant impact on bone level included: autoimmune disease, heavy smoking, bisphosphonate therapy, implant location, diameter and design, and the presence of a bone defect at site of implantation. The prevalence of mucositis at the implant level was 38.6% versus 14.2% at 6 to 7 years, when using strict versus relaxed criteria, respectively. The prevalence of peri‐implantitis after 6 to 7 years was 4.7% and 3.6% when using strict versus relaxed criteria, respectively.ConclusionsThe results of this study identify several risk factors associated with bone loss. Furthermore, the prevalence of mucositis and peri‐implantitis was shown to be lower at both the implant and the patient when using strict versus relaxed criteria based on the assessment of oral health surrounding dental implants.

Prognostic criteria of variceal bleeding in patients with portal hypertension

Aim. To determine prognostic criteria of variceal bleeding in patients with portal hypertension.Material and methods. There were 53 patients with portal hypertension and the threat of variceal bleeding from the esophagus and stomach without previous hemorrhage. Univariate and multivariate analysis was applied to determine prognostic criteria of the first bleeding. Patients with esophageal and gastroesophageal varices were analyzed separately. The following prognostic criteria were considered: dimensions of the veins, vasculopathy and gastropathy, liver function.Results. Incidence of hemorrhage was 72.7% in patients with esophageal varices grade 3, in case of vasculopathy — 80%. Child-Pugh class A was followed by incidence of hemorrhage near 12.5%, class B — 44%, C — 100%. MELD score &lt; 9 was associated with bleeding rate 28.6%, 10—19 — 39.3%, over 20 scores — 100%. According to multivariate analysis consisting of Child—Pugh classification, in patients with &lt; 11 scores 1-year incidence of bleeding was 13.3%, in case of MELD classification — 16.7%. The same values in patients with 11—16 scores were 77.8% and 31.3%, respectively. Analysis including both classifications (overall score over 16) was associated with incidence of hemorrhage up to 100%. Gastroesophageal varices grade 3 were associated with the risk of hemorrhage near 44.4% within 12 months, in case of vasculopathy — 60%, gastropathy — 37.5%. Incidence of hemorrhage in patients with Child-Pugh class A was 12.5%, class B — 44%, class C — 100%. In patients with MELD score &lt; 9 bleeding rate was 28.6%, 10—19 scores — 39.3%, over 20 scores — 100%. According to multivariate analysis consisting of Child—Pugh classification, patients with gastroesophageal varices and less than 11 scores have the probability of hemorrhage near 15.4% within 12 months, in case of MELD score — 23%. The same values were 55.6% and 50%, respectively in case of 11—18 scores. In patients with more than 18 scores incidence of hemorrhage was 75% considering Child-Pugh classification and 100% for the MELD classification.Conclusion. The group of patients with threat of bleeding within 12 months was determined that makes possible a differentiated approach to patients who for need primary prevention of bleeding.

Anticoagulation of a Percutaneous Left Ventricular Assist Device Using a Low-Dose Heparin Purge Solution Protocol: A Case Series

Background Impella CP® is a percutaneous left ventricular assist device that requires a heparin–dextrose purge solution. The manufacturer recommends heparin 50 units/mL, but supratherapeutic anticoagulation has been observed with this concentration. Objective The purpose of this evaluation was to observe the efficacy and safety of a low-dose heparin-based purge solution (25 units/mL in dextrose 20%). The primary outcome evaluated percentage of activated clotting times (ACTs) below therapeutic range. Secondary objectives included evaluating the incidence of device thrombosis and rate of heparin-induced thrombocytopenia (HIT). Platelet trends were characterized. Methods A single-site retrospective review was conducted for all adults with the Impella CP from January 2015 to December 2017. Results A total of 18 patients were included. The percentage of ACT readings within goal of 160 to 200 seconds was 49%, and 38% of readings were subtherapeutic. Per BARC bleeding criteria, 22% (n = 4) patients experienced class IIIa bleeding and 39% (n = 7) experienced class II bleeding. Though 4 (22%) patients were tested for HIT, no patients were positive. Patients showed universal reductions in platelet counts. Conclusions The use of a low-dose anticoagulation protocol of heparin 25 units/mL in dextrose 20% as needed warrants further evaluation.

Ultrasound Guided Technique for Percutaneous Transfemoral Transcatheter Aortic Valve Implantation

Aim/objective: The aim of this study was to determine the outcomes of ultrasound-guided technique for patients undergoing percutaneous transfemoral transcatheter aortic valve implantation (TF-TAVI) to prevent vascular complications. Method: We report a single centre analysis of 154 patients of a prospectively collected cohort between who underwent transfemoral TAVI using the balloon-expandable Edwards SAPIEN 3 transcatheter heart valve. Patients were divided into two groups (non ultrasound-guided puncture group who underwent TAVI n = 86 compared to those patients who underwent ultrasound-guided puncture n = 68.) The incidence of major vascular complications as defined by The Valve Academic Research Consortium - 2 Criteria (VARC2 criteria) and bleeding complications as defined by the Bleeding Academic Research Consortium (BARC) were used as outcome measures. Results: The incidence of major access site related complications were low and were numerically reduced with ultrasound guided puncture (4.65% vs 0.0%; p = 0.135.) BARC Bleeding criteria greater or equal to 3 was similar between groups (2.33% vs 1.47%; p = NS). Conclusion: This study demonstrates a numerical trend to improved outcomes following the use of ultrasound-guided percutaneous transfemoral puncture for TAVI. This technique has been shown to prevent vascular complications as defined by VARC2 criteria.

Comparison of clinical prediction tools and identification of risk factors for adverse outcomes in acute lower GI bleeding

Limited data exist on prediction of adverse outcomes in patients with acute lower GI bleeding (LGIB). The purpose of our study was to compare the ability of existing validated clinical risk scores to predict relevant outcomes in LGIB. We performed a prospective observational study of patients admitted with LGIB who underwent colonoscopy at a single center between April 2016 and September 2017. Seven risk scores were calculated at admission (Strate, NOBLADS, Sengupta, Oakland, Blatchford, AIMS65, and Charlson Comorbidity Index). The risk of severe LGIB was determined via univariable and multivariable logistic regression. Area under the receiver operating characteristic curve (AUC) analysis was used to compare the scores. We included 170 patients admitted with LGIB requiring colonoscopy. Fifty-two percent (n= 89) fit criteria for severe bleeding. Patients with severe bleeding had lower admission hemoglobin levels (8.6 g/dL vs 11.1 g/dL; P= .0001), were more likely to have blood transfusions (85% vs 36%; P< .0001), intensive care unit stays (49% vs 19%; P< .0001), and had a longer length of stay (6 days vs 4 days; P= .0009). The Oakland score was best for prediction of severe bleeding (AUC, .74), Blatchford score for blood transfusion (AUC, .87), and Strate score for in-hospital recurrent bleeding (AUC, .66) and endoscopic intervention (AUC, .62). The strongest individual predictors of severe bleeding were low admission hemoglobin (odds ratio, 1.28 per 1-g/dL decrease; P= .0015; 95% confidence interval, 1.10-1.49) and low albumin (odds ratio, 2.56 per 1-g/dL decrease; P= .02; 95% confidence interval, 1.16-5.56). Admission albumin and hemoglobin levels were the strongest predictors of severe bleeding. No singular clinical risk tool had the best predictive ability across all outcomes.