Significant Difference In Bleeding Rates Research Articles

Hetrombopag plus recombinant human thrombopoietin for chemotherapy-induced thrombocytopenia in patients with solid tumors

BackgroundChemotherapy-induced thrombocytopenia (CIT) is a common hematological complication in patients with cancer. Hetrombopag is a novel thrombopoietin receptor agonist that has shown an additive effect in stimulating platelet production when combined with recombinant human thrombopoietin (rhTPO). ObjectivesThis multicenter retrospective cohort study aimed to evaluate the efficacy and safety of hetrombopag plus rhTPO compared with rhTPO alone for CIT. MethodsA total of 294 patients with solid tumors and CIT (platelet count, <50 × 109/L) who received either rhTPO plus hetrombopag (146 patients) or rhTPO alone (148 patients) at 3 centers from January to December 2022 were included in the study. The primary outcome was a platelet count at least 50 × 109/L higher than the baseline value within 14 days. Chemotherapy dose reductions/delays, bleeding, and adverse events were reported. ResultsOne hundred twenty patients (82.2%) in the rhTPO-hetrombopag group vs 100 patients (67.6%) in the rhTPO group achieved the primary outcome (P = .005). This significant difference persisted in adjusted analysis (odds ratio, 2.01; 95% CI, 1.12-3.60). A total of 115 patients (78.8%) in the rhTPO-hetrombopag group and 101 patients (68.2%) in the rhTPO group avoided chemotherapy dose reductions/delays (P = .041). There was no significant difference in bleeding rates, and adverse events were mild and similar between the 2 groups. No deaths occurred. ConclusionCompared to rhTPO alone, our findings suggest that the combination of hetrombopag and rhTPO is safe and more effective in patients with CIT.

Effect of renal insufficiency on the short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer: Propensity score-matched analysis.

It is unclear whether renal insufficiency (RI) itself is a risk factor for adverse outcomes after gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the safety and efficacy of gastric ESD in patients with and without RI using propensity score-matching analysis. In all, 4775 patients with 4775 early gastric cancer lesions undergoing ESD were analyzed. 1:1 propensity score-matching was performed between patients with and without RI using 12 variables. After matching, logistic regression and survival analyses were performed for short- and long-term outcomes of ESD, respectively. The matching yielded 188 pairs of patients with and without RI. In both univariable and multivariable analyses, the presence of RI was not significantly associated with postprocedural bleeding (unadjusted odds ratio 1.81, 95% confidence interval 0.74-4.42; adjusted odds ratio 1.86, 95% confidence interval 0.74-4.65, respectively). When RI patients were subclassified into patients with estimated glomerular filtration rate (eGFR) 30-59 mL/min/1.73 m2 and eGFR <30 mL/min/1.73 m2 , no significant differences in bleeding rates were found compared to their matched controls in both groups. Perforation, en bloc resection, en bloc and R0 resection, and curative resection rates of RI patients were 2.1%, 98.4%, 91.0%, and 78.2%, respectively, which were comparable to those of non-RI patients. During a median follow-up of 119 months, there was no difference in gastric cancer-specific survival between patients with and without RI (P = 0.143). The outcomes of ESD were comparable in patients with and without RI. Decreased renal function itself may not be a reason to keep patients with RI from receiving gastric ESD.

Endoscopic N-butyl-2-cyanoacrylate and ethanolamine oleate injection is equivalent to balloon-occluded retrograde transvenous obliteration for preventing gastric variceal bleeding.

Endoscopic injection sclerotherapy (EIS) is effective for temporary hemostasis, but EIS and balloon-occluded retrograde transvenous obliteration (BRTO) have been reported as effective for secondary prophylaxis of gastric varices (GV) bleeding. This study retrospectively compared EIS and BRTO in patients with GV in terms of the efficacy for secondary prevention of GV bleeding and effects on liver function. From our database of patients with GV who underwent EIS or BRTO between February 2011 and April 2020, a total of 42 patients with GV were retrospectively enrolled. The primary endpoint was the bleeding rate from GV, which was compared between EIS and BRTO groups. Secondary endpoints were liver function after treatment and rebleeding rate from EV, compared between EIS and BRTO groups. Rebleeding rates from GV and EV and liver function after treatment were also compared between EIS-ethanolamine oleate (EO)/histoacryl (HA) and EIS-HA groups. Technical success was achieved for all EIS cases, but two cases were unsuccessful in the BRTO group and underwent additional EIS. No significant differences in bleeding rates or endoscopic findings for GV improvement were seen between EIS and BRTO groups. Liver function also showed no significant difference in the amount of change after treatment between groups. EIS therapy appears effective for GV in terms of preventing GV rebleeding and effects on liver function after treatment. EIS appears to represent an effective treatment for GV.

The impact of thrombocytopenia on variceal bleeding in cirrhotic patients with transjugular intrahepatic portosystemic shunt

Thrombocytopenia is the most frequent haematologic disorder in patients with cirrhosis, and it is perceived as a contributory factor for bleeding events. Cirrhosis patients with portal hypertension (PHT) is often accompanied with mild to moderate thrombocytopenia when they treated with transjugular intrahepatic portosystemic shunt (TIPS). To address whether the risk of variceal hemorrhage after TIPS varies with different platelet count in patients with normal platelet count and thrombocytopenia, we conducted the retrospective controlled study to evaluate the association of platelet count with the risk of variceal bleeding after TIPS. 304 patients were selected to the study. Propensity score matching was performed to adjust for potential selection bias. 63 patients from each group could be paired. Cox proportional hazards models were used to evaluate the association between platelet and variceal bleeding after TIPS. Platelet counts of two groups are 185.0 ± 98.7 × 109/L (normal platelet count) and 70.6 ± 39.3 × 109/L (thrombocytopenia) respectively. The bleeding rates of two groups in overall cohort are 10.9% (normal platelet count) and 12.9% (thrombocytopenia). After matched, the bleeding rates of two groups are 11.1% (normal platelet count) and 14.3% (thrombocytopenia) There was no statistically significant difference in bleeding rates between the two groups, either in the whole cohort (P = 0.671) or in the matched cohort (P = 0.593). Platelet count was not associated with bleeding events after TIPS (hazard ratio (HR) 95% confidence interval: 0.986–1.005, P = 0.397 in normal platelet count and 95% confidence interval: 0.968–1.020, P = 0.648 in thrombocytopenia). Thrombocytopenia in patients with cirrhosis was not associated with the risk of variceal bleeding episodes post-TIPS. Thrombocytopenia should not be viewed as an absolute contraindication for TIPS.

Does infection play a role in post-tonsillectomy haemorrhage? A narrative review.

Post-tonsillectomy haemorrhage is an increasingly common cause of morbidity following tonsillectomy. Secondary post-tonsillectomy haemorrhage occurring more than 24 hours after an operation has long been attributed to post-operative infection; however, there is little evidence to support this hypothesis and the associated use of antibiotics in the current literature. This study looked at the aetiology and evidence-based management of post-tonsillectomy haemorrhage, and investigated the impact of bacterial infection and antimicrobials on the pathogenesis and clinical course of this complication. A number of peri-operative risk factors for post-tonsillectomy haemorrhage exist, and infective pathologies, including recurrent or chronic tonsillitis and group A streptococcus on blood cultures, may predispose to bleeding. Very few studies have shown a link between post-tonsillectomy haemorrhage and objective markers of infection such as pyrexia, raised inflammatory markers or positive microbiology cultures. The role of antibiotics in secondary post-tonsillectomy haemorrhage remains controversial, and numerous randomised, controlled trials of peri-operative antibiotics have shown no significant difference in bleeding rates between antibiotics and controls. Further trials investigating the role of antibiotics and more robust studies investigating the presence of bacterial infection at the time of bleeding may be required to determine the true role of infection in post-tonsillectomy haemorrhage.

Population based study of morbidity and mortality rates associated to radical prostatectomy cases in Spain

IntroductionThere is no population-based study that accounts for the number of radical prostatectomies (RP) carried out in Spain, nor regarding the morbidity and mortality of this intervention.Our objective is to study the morbidity and mortality of RP in Spain from 2011 to 2015 and to evaluate the geographic variation. Material and methodsWe designed a retrospective observational study of all patients submitted to RP in Spain during five consecutive years (2011–2015). The data was extracted from the «Conjunto Mínimo Básico de Datos» (CMBD).We have evaluated geographic variations in terms of morbidity and hospital stay, and the impact of the mean annual surgical volume for each center on these variables. ResultsBetween 2011–2015, a total of 37,725 RPs were performed in 221 Spanish public hospitals. The mean age of the series was 63.9±3.23 years. Of all RPs, 50% were performed through an open approach, and 43.4% have been operated on in hospitals with <500 beds. We observed an important variability in the distribution of the cases operated on in the different regions. The regions that perform more RPs are Andalusia, Catalonia, Galicia, and Madrid. Our study shows a complication rate of 8.6%, with hemorrhage and the need for transfusion being the most frequent (5.3 and 4%, respectively). There are significant differences in bleeding rates and hospital stay among regions, which are maintained after adjusting for patient characteristics and type of hospital. When studying the annual surgical volume of each hospital, we find that the impact on the rate of hemorrhage or transfusion is linear; however, hospital stay remains stable at around 5 days from 60 RPs/year. ConclusionsIn national terms, morbidity and mortality rates after RP are comparable to those described in the literature. This study reveals a clear dispersion in the hospitals that carry out this intervention, showing clear differences in terms of morbidity and hospital stay between the different regions.

Prevention of Cardioembolic Complications in Patients with Atrial Fibrillation: Efficacy and Safety of Left Atrial Appendage Isolation and Oral Anticoagulants

Aim. To study the outcomes frequency and structure in patients with atrial fibrillation (AF) depending on the cardioembolic events preventing method: left atrial appendage (LAA) isolation, direct oral anticoagulants (DOACs) or warfarin.Material and methods. A prospective observational study included patients with AF and high risk of cardioembolic complications and without contraindications to anticoagulants. Patients who refused long-term oral anticoagulants taking underwent LAA isolation, the rest of the patients received DOACs or warfarin. The observation period was 3 years. Mortality, cardioembolic complications and major bleeding (according to GARFIELD criteria) cumulative incidence was assessed.Results. We included 245 patients: 46 patients were treated with LAA isolation, 100 with warfarin, and 99 with DOACs. Multivariate regression analysis demonstrated a statistically significant advantage of LAA occluder in terms of combined endpoint achieving frequency compared to warfarin (hazard ratio [HR] 3.10; 95% confidence interval [CI] 1.01-9.54; p=0.049), and to DOACs (HR 3.44, 95% CI 1.15-10.29; p=0.027). A similar result was obtained for all-cause mortality (HR 5.24; 95% CI 1.12-24.55; p=0.036 and HR 5.58; 95% CI 1.22-25.49; p=0.027, respectively). There were no significant differences in bleeding rates between the groups.Conclusion. This observational study demonstrates the superiority of LAA isolation as a first-line therapy over DOACs and warfarin in patients with AF and high risk of cardioembolic complications. Randomized trials are required to confirm these observations.

Estudio poblacional de casuística y morbimortalidad de la prostatectomía radical en España

IntroductionThere is no population-based study that accounts for the number of radical prostatectomies (RP) carried out in Spain, nor regarding the morbidity and mortality of this intervention.Our objective is to study the morbidity and mortality of RP in Spain from 2011 to 2015 and to evaluate the geographic variation. Material and methodsWe designed a retrospective observational study of all patients submitted to RP in Spain during five consecutive years (2011-2015). The data was extracted from the «Conjunto Mínimo Básico de Datos» (CMBD).We have evaluated geographic variations in terms of morbidity and hospital stay, and the impact of the mean annual surgical volume for each center on these variables. ResultsBetween 2011-2015, a total of 37,725 RPs were performed in 221 Spanish public hospitals. The mean age of the series was 63.9 ± 3.23 years. Of all RPs, 50% were performed through an open approach, and 43.4% have been operated on in hospitals with < 500 beds. We observed an important variability in the distribution of the cases operated on in the different regions. The regions that perform more RPs are Andalusia, Catalonia, Galicia, and Madrid. Our study shows a complication rate of 8.6%, with hemorrhage and the need for transfusion being the most frequent (5.3 and 4%, respectively). There are significant differences in bleeding rates and hospital stay among regions, which are maintained after adjusting for patient characteristics and type of hospital. When studying the annual surgical volume of each hospital, we find that the impact on the rate of hemorrhage or transfusion is linear; however, hospital stay remains stable at around 5 days from 60 RPs/year. ConclusionsIn national terms, morbidity and mortality rates after RP are comparable to those described in the literature. This study reveals a clear dispersion in the hospitals that carry out this intervention, showing clear differences in terms of morbidity and hospital stay between the different regions.

A Retrospective Analysis of q12hr and q8hr Heparin for DVT/PE Prophylaxis in an Inpatient Rehabilitation Setting.

Purpose: There is little clinical evidence comparing the safety and efficacy of prophylactic subcutaneous heparin given every 8 hours and every 12 hours. We performed a retrospective analysis incorporating these dosing intervals in an inpatient rehabilitation setting. Methods: Heparin usage data was collected and patient charts were analyzed for both therapeutic failure and bleeding events. A 2-tailed Fisher's exact test was performed for both outcomes, with a P-value of less than 0.05 being considered significant. Odds ratios were also calculated with P-values less than 0.05 being considered significant. Study Population: A Cerner report was run to identify patients ordered prophylactic heparin in an inpatient rehabilitation setting from April 7, 2020, to October 27, 2021. One hundred patients receiving heparin every 8 hours and every 12 hours were randomly selected for chart review. These study groups were further stratified by Padua risk scores. Results: In both groups, 4 (4.0%) patients were identified as having a documented bleeding event and 2 (2.0%) patients from each group were identified as having a therapy failure. Conclusion: For both endpoints, no significant differences in bleeding rates or therapy failure rates were detected in any of the population stratifications.

Effects of Aspirin Therapy on Bypass Efficacy and Survival of Patients Receiving Direct Cerebral Revascularization.

Background: Both patency maintenance and neoangiogenesis contribute to cerebrovascular bypass efficacy. However, the combined impact of the aforementioned two indicators on postoperative revascularization following superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass has been less well elucidated. Meanwhile, there is a paucity of evidence with conflicting results about postoperative aspirin therapy. Objective: The objective of the study was to investigate the correlation between aspirin use and STA-MCA bypass efficacy, including patency, postoperative neoangiogenesis, and follow-up outcomes. Methods: A total of 181 MMD patients (201 procedures) undergoing STA-MCA bypass at our institution (2017–2019) were retrospectively reviewed. The bypass efficacy level and postoperative complications were compared between aspirin and non-aspirin groups. Results: Among 95 PS-matched pairs, the aspirin group presented a significantly more favorable bypass efficacy than the non-aspirin group [odds ratio (OR) 2.23, 95% confidence interval (CI) 1.11–4.61; p = 0.026]. Multivariate logistic regression analysis confirmed the profound impact of aspirin as an independent predictor of bypass efficacy [adjusted OR 2.91, 95% CI 1.34–6.68; p = 0.009]. A remarkable negative correlation was found between bypass efficacy and the rate of ischemic complications (Phi = −0.521). Postoperative aspirin therapy was associated with a non-significant trend toward a lower incidence of ischemic events [OR 0.73, 95% CI 0.23–2.19; p = 0.580]. No significant difference in bleeding rates was observed between aspirin and control groups [OR 1.00, 95% CI 0.12–8.48; p = 1.000]. Conclusion: Among patients undergoing STA-MCA bypass procedures, bypass efficacy is a good predictor of follow-up outcomes. Postoperative aspirin therapy can improve patency, neoangiogenesis, and overall bypass efficacy, thereby protecting against postoperative ischemic complications. Clinical Trial Registration: http://www.chictr.org.cn/, identifier CTR2100046178.

Immediate postoperative color Doppler ultrasonography on the diagnosis of hemorrhagic complications of liver biopsy and its directed compression hemostasis

Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.

Procedure-related risk factors for bleeding after percutaneous transhepatic biliary drainage: A systematic review and meta-analysis

Bleeding is the most dreaded complication after percutaneous transhepatic biliary drainage (PTBD). Clarifying the risk factors of bleeding can reduce the morbidity and mortality rates of PTBD. However, the procedure-related risk factors for bleeding after PTBD are still controversial. Therefore, this systematic review and meta-analysis were performed to identify procedure-related risk factors of bleeding after PTBD. PubMed, Cochrane database, and Google Scholar were searched for published studies until 1st May 2021. Inclusion criteria were: studies associated with bleeding complications after PTBD and with sufficient data to compare different procedure-related factors for bleeding. Sources of bias were assessed using the Newcastle-Ottawa Scale and Cochrane risk-of-bias tool for randomised trials. Probable procedure-related risk factors were evaluated and outcomes were expressed in the case of dichotomous variables, as an odds ratio (OR) (with a 95% confidence interval, (CI)). Eleven studies were included in the meta-analysis. There was no significant difference in bleeding rates with respect to the side of PTBD (left/right, OR=1.10, 95% CI: 0.68-1.76), the insertion level of bile duct (central/peripheral, OR=1.39, 95% CI: 0.82-2.35), and the usage of ultrasound guidance (OR: 1.25, 95% CI: 0.60-2.60). A subgroup analysis revealed a left-sided approach that resulted in more hepatic arterial injuries than the right-sided approach (left/right, OR=1.93, 95% CI: 1.32-2.83). Left-sided approach is a risk factor for hepatic arterial injuries after PTBD.

A Cross-Sectional Study of the American Thrombosis and Hemostasis Network Dataset for Outcomes of Dental Extractions in People with Hemophilia

BACKGROUND: Dental extraction (DE) is one of the most common procedures in people with hemophilia A or hemophilia B (PWH-A, PWH-B), yet little is known about impact of the type of hemophilia, hemostatic therapies, and bleeding outcomes. To date, there is no standard protocol for how to treat PWH undergoing DE. Similar overall bleeding rates occur with pre- and postoperative factor replacement (FRP) therapy and single dose preoperative FRP (11.9% and 11.4%, respectively) (DE. Bajkin et al. Haemophilia 2020).METHODS: We analyzed the American Thrombosis and Hemostasis Network dataset (ATHNdataset) to assess trends in prophylactic factor use and its impact on bleeding outcomes following dental extraction in PWH-A and PWH-B ≥2 years of age. A DE bleeding episode was defined as any oral or mouth bleeding occurring during or within one week following a DE procedure. Treated bleeds were defined as any oral or mouth bleeds treated with hemostatic medications during or within one week post-DE. Hospitalization and emergency department (ED) visit events were defined as any that occurred during or one day after a DE. Data on sociodemographic, clinical characteristics, and outcomes were collected prospectively between 2013 and 2019 at annual clinical visits to 134 ATHN-affiliated sites. Categorical variables were summarized using frequency and percentage. Logistic regression was used to evaluate associations between DE and sociodemographic and clinical variables. Simple logistic regression models were applied to identify factors potentially associated with dental bleeding episodes among PWH.RESULTS: Sociodemographic and clinical characteristics revealed that of the 19,048 PWH in the ATHNdataset, 1,157 subjects underwent 1,301 episodes of DE; a majority (74.9%) were diagnosed hemophilia A and 94.4% were male. The odds of a DE were approximately 148% higher among male PWH compared to female PWH (OR: 2.48; 95%CI: 1.93-3.20). PWH with severe disease were less likely to undertake DE than those with mild hemophilia (OR: 0.83; 95%CI: 0.72-0.95). Compared to PWH-B, PWH-A tended to have DEs at a younger age (<30 years). The chance of a DE did not differ by race, hemophilia type, and currently having or having a history of inhibitor. No significant associations were found between dental extraction, education or employment among PWH ages >18 years.Dental extraction clinical outcomes and related treatments indicated approximately 34% of PWH used prophylaxis versus on-demand therapy (18%) 292for dental/mouth bleeding. Approximately 5% of PWH who underwent DE reported oral/mouth bleeds within one week of the procedure. Of those bleeding episodes, 28.0% of hemophilia A patients and 12.5% of hemophilia B patients reported two or more oral/mouth bleeds during, and one-week post-DE. Rates of hospitalizations and ED visits were 7.4% and 1.3% respectively for PWH-A and 8.8% and 0.9% respectively for PWH-B. Among oral/mouth bleeds related to dental extraction, 34.0% and 50.0% patients with hemophilia A and B respectively received hemostatic therapies such as DDAVP, factor concentrates, or antifibrinolytics.Factors associated with DE bleeding were as follows: Dental extractions performed with prophylactic regimen were found to experience insignificantly fewer dental bleeding episodes (P>0.05). Similarly, no statistically significant difference in bleeding rate after DE was found in those using extended half-life factor (EHL) compared to standard half-life products (SHL). Prophylaxis was more prevalent among PWH-A compared to PWH-B (37.3% vs. 25.2% respectively). SHL products were more commonly used than EHL products for on-demand therapy (8.3% vs. 0.5% respectively) as well as prophylaxis (19.8% vs. 8.1%). PWH who have ever developed an inhibitor significantly increased the odds of dental bleeding (OR:2.09, 95%CI: 1.21-3.63). However, no significant relationship was found between inhibitor and DE bleedings among PWH who have been exposed to emicizumab (P=0.168).DISCUSSION: This is the largest study of DE outcomes in PWH. DE tends to be performed more in those with mild hemophilia and at an earlier age. The use of hemostatic therapies and factor prophylaxis is associated with insignificantly less bleeding. The ATHNdataset allowed studies of outcomes in a large cohort of PWH. This project was part of the ATHN CARE Award. DisclosuresHe: ATHN: Ended employment in the past 24 months. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment. Kulkarni: Bayer: Consultancy, Research Funding; CSL Behring: Consultancy; Genentech/Roche: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Catalyst Bioscience: Research Funding; Foundation for Women and Girls with Blood Disorders: Membership on an entity's Board of Directors or advisory committees.

Incidence and Predictors of Thrombotic Complications in 4742 Patients with COVID-19 or Other Acute Infectious Respiratory Diseases: A Propensity Score-Matched Study.

Background. A prothrombotic state, attributable to excessive inflammation, cytokine storm, hypoxia, and immobilization, is a feature of SARS-CoV-2 infection. Up to 30% of patients with severe COVID-19 remain at high risk of thromboembolic events despite anticoagulant administration, with adverse impact on in-hospital prognosis. Methods. We retrospectively studied 4742 patients with acute infectious respiratory disease (AIRD); 2579 were diagnosed to have COVID-19 and treated with heparin, whereas 2163 had other causes of AIRD. We compared the incidence and predictors of total, arterial, and venous thrombosis, both in the whole population and in a propensity score-matched subpopulation of 3036 patients (1518 in each group). Results. 271 thrombotic events occurred in the whole population: 121 (4.7%) in the COVID-19 group and 150 (6.9%) in the no-COVID-19 group (p < 0.001). No differences in the incidence of total (p = 0.11), arterial (p = 0.26), and venous (p = 0.38) thrombosis were found between the two groups after adjustment for confounding clinical variables and in the propensity score-matched subpopulation. Likewise, there were no significant differences in bleeding rates between the two groups. Clinical predictors of arterial thrombosis included age (p = 0.006), diabetes mellitus (p = 0.034), peripheral artery disease (p < 0.001), and previous stroke (p < 0.001), whereas history of solid cancer (p < 0.001) and previous deep vein thrombosis (p = 0.007) were associated with higher incidence of venous thrombosis. Conclusions. Hospitalized patients with COVID-19 treated with heparin do not seem to show significant differences in the cumulative incidence of thromboembolic events as well as in the incidence of arterial and venous thrombosis separately, compared with AIRD patients with different etiological diagnosis.

Direct Oral Anticoagulants for the Prevention of Recurrent Venous Thromboembolism: A Systematic Review & Network Meta-Analysis

Background:Several studies have reported the superiority of extended anticoagulation with rivaroxaban, apixaban, dabigatran and aspirin as superior to placebo for the prevention of recurrent venous thromboembolism (VTE). However, it is unknown if this is a class effect applicable to all direct oral anticoagulants (DOACs) or if one agent is superior. Network meta-analysis allows for indirect comparisons of agents or interventions that have not been formally evaluated in head-to-head trials while preserving randomization of the original trials.Methods:We performed a systematic review and network meta-analysis of randomized controlled trials that compared extended anticoagulation with DOACs to other oral agents (e.g., another DOAC, aspirin or placebo) for the prevention of recurrent VTE. We excluded data on extended treatment with vitamin K antagonists or low-molecular-weight-heparin. Data extraction and assessment of methodological quality with the GRADE approach was assessed by two independent reviewers and verified by the primary investigator. Effect size estimates were calculated and pooled using techniques of network meta-analysis. Effect size was expressed as hazard ratios and 95% confidence intervals.Results:Six randomized trials with a total of 9,610 participants were analyzed. All trials were of high methodological quality. Prior to randomization, all participants had completed an initial period of anticoagulation for an index VTE event; the majority were treated for 6 to 18 months for an unprovoked event prior to starting extended treatment for VTE prevention. Two trials compared low-dose aspirin (100 mg daily) to placebo (ASPIRE and WARFASA), one compared rivaroxaban 10 mg or 20 mg daily to low-dose aspirin (EINSTEIN CHOICE), and the others evaluated rivaroxaban 20 mg daily (EINSTEIN-EXT), apixaban 2.5 mg or 5 mg twice-daily (AMPLIFY-EXT) and dabigatran 150 mg twice-daily (RE-SONATE) versus placebo for the prevention of recurrent VTE. The results are summarized in Figure 1b. Compared to placebo, aspirin and all DOACs effectively reduced VTE recurrence. Apixaban, rivaroxaban, and dabigatran were superior to aspirin and demonstrated comparable efficacy in preventing VTE recurrence. There was no statistically significant difference in bleeding rates between any agents compared to placebo.Conclusion:Our results demonstrate that all DOACs can be used interchangeably for secondary prophylaxis of VTE, likely due to a drug class effect. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Bleeding Outcomes of Gastrointestinal Cancer Patients Treated with Direct Oral Anticoagulants Vs. Low Molecular Weight Heparin

Introduction: In recent years, direct oral anticoagulants (DOACs) have been adopted as a treatment option for cancer associated thrombosis (CAT). Randomized trials comparing anti-Xa drugs to low molecular weight heparin (LMWH) showed treatment with DOACs conferred less risk of recurrent venous thromboembolism (VTE), but found higher rates of clinically important bleeding, especially in patients with gastrointestinal (GI) malignancies. Given these findings, there is a need for additional data regarding the safety of DOAC use in GI malignancies. Here, we report bleeding events of GI cancer patients treated with anticoagulation in a large centralized CAT clinic. Methods: We evaluated a prospective cohort of patients referred to our CAT clinic from 8/2014-10/2019. Patients with primary gastrointestinal malignancies treated with therapeutic anticoagulation with LMWH or a DOAC for acute VTE were included. Bleeding was defined using the ISTH criteria for major and clinically relevant non-major bleeding (CRNMB). Bleeding rates were compared between luminal [anus/anal, colon, esophagus, rectal, stomach] and extraluminal GI cancers [gallbladder, liver/bile duct, and pancreas]. Patient characteristics associated with bleeding were evaluated with Fisher's exact test and the association of age with bleeding was analyzed by Wilcoxan rank sum test. Results: Of 463 patients with acute VTE, 73 patients (15.8%) with primary GI tumors were included in the analysis. Males comprised 57.5% of the population, median age was 62 (range 36-86), and 61.6% had stage 4 disease. Figure 1 shows a breakdown of tumor types. Enoxaparin was the most commonly used anticoagulant (n=48, 65.8%), followed by DOAC (n=25, 34.2%). Overall, 16 (21.9%) patients had a bleeding event within 6 months of treatment (7 major bleeds and 9 CRNMB). There was no difference in 6-month bleeding rate between patients treated with LMWH (n= 9, 18.8%) vs. DOAC (n=7, 28.0%), p=0.39. None of the clinical factors analyzed were significantly associated with bleeding (Table 1). There was no difference in bleeding rate in patients with luminal GI cancers vs. extraluminal GI cancers and no difference was found in a three-way association between site, treatment, and bleeding, p=0.40 (Table 2). Conclusions: In our centralized cancer thrombosis clinic, patients with GI malignancies had similar rates of major and CRNMB when treated with LMWH or DOAC. In both cohorts, bleeding rates were high within 6 months of starting anticoagulation. There were no statistically significant differences in bleeding rates based on several clinical characteristics evaluated in this study. Although limited by a small patient population, this study adds to the knowledge of treating GI malignancies with DOACs. There is a need for further prospective evaluations regarding the safety of DOAC use in GI cancer patients and there remains an unmet need for antithrombotic treatments that do not increase bleeding potential. Disclosures McCrae: Novartis: Honoraria; Momenta Pharmaceuticals: Consultancy; Rigel: Consultancy; Dova: Consultancy. Khorana:Bayer: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Merck: Research Funding; Leap: Research Funding; BMS: Honoraria, Research Funding; Seattle Genetics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Janssen: Honoraria.

Clinical factors related to successful or unsuccessful cardioversion in the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) randomized trial.

BackgroundEdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation evaluated use of nonvitamin K antagonist oral anticoagulant edoxaban vs enoxaparin‐warfarin in patients with nonvalvular atrial fibrillation undergoing electrical cardioversion.HypothesisTo assess clinical factors related to successful or unsuccessful cardioversion. To evaluate whether differences in adverse events based on anticoagulation strategy may exist.MethodsIn this multicenter prospective randomized open‐label blinded end‐point evaluation trial, 2199 patients were randomized to edoxaban 60 mg once daily (30 mg for creatinine clearance 15‐50 mL/min, weight ≤ 60 kg, and/or concomitant use of P‐glycoprotein inhibitor) or enoxaparin‐warfarin. Successful cardioversion was confirmed by 12‐lead electrocardiography‐documented sinus rhythm.ResultsCardioversion was successful in 1578 patients; in 355 patients, cardioversion was unsuccessful. Male, high body weight, high body mass index (BMI), coronary artery disease, concomitant aspirin, or prior statins use were more common in patients with unsuccessful cardioversion; international normalized ratio control did not differ by cardioversion success. On multivariate analysis, gender (P < .05), body weight (P = .0196) and BMI (P = .0377) emerged as independent predictors of successful cardioversion. There were no significant differences in primary efficacy (a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death during overall study period) regardless of cardioversion success. There were no significant differences in bleeding rates, regardless of cardioversion outcome; notwithstanding low numbers, edoxaban and enoxaparin‐warfarin did not differ.ConclusionsMale gender, higher mean weight and higher mean BMI were associated with unsuccessful cardioversion. Efficacy and safety outcomes were low and did not differ by cardioversion success.

Comparing TEE‐ vs Non–TEE‐guided cardioversion of atrial fibrillation: The ENSURE‐AF trial

ENSURE-AF (NCT02072434) assessed therapy with edoxaban vs enoxaparin-warfarin in patients with nonvalvular atrial fibrillation (AF) undergoing elective electrical cardioversion (ECV). To evaluate clinical features and primary efficacy (composite of stroke, systemic embolic events, myocardial infarction and cardiovascular mortality during study period) and safety endpoints (composite of major and clinically relevant nonmajor bleeding during on-treatment period) in patients awaiting ECV of AF with a transesophageal echocardiography (TEE)-guided vs a non-TEE-guided strategy. In this prospective, randomized, open-label, blinded endpoint study, 2199 patients were randomized to edoxaban 60mg once-daily (30mg for creatinine clearance 15-50mL/min, weight ≤60kg and/or concomitant use of P-glycoprotein inhibitor) or enoxaparin-warfarin. Primary efficacy endpoint and safety endpoint were reported. Associates of TEE use, efficacy endpoint and safety endpoint were explored using multivariable logistic regression. In total, 589 patients from the edoxaban stratum and 594 from the enoxaparin-warfarin stratum were allocated to the TEE-guided strategy. Primary efficacy was similar regardless of TEE approach (P=.575). There were no significant differences in bleeding rates, regardless of TEE approach (P=.677). Independent predictors of TEE use were as follows: history of ischaemic stroke/ transient ischaemic attack, hypertension and valvular heart disease. Mean CHA2 DS2 VASc and HAS-BLED score were independent predictors of the efficacy endpoint whilst mean age was an independent predictor of the safety endpoint. Thromboembolic and bleeding events were not different between patients undergoing TEE-guided strategy and in those undergoing an optimized conventional anticoagulation approach for ECV of AF.

Prevention of venous thromboembolism with rivaroxaban and apixaban in orthopedic surgery

Numerous limitations and side effects of standard anticoagulants require administering new anticoagulant drugs. New peroral anticoagulants of Factor Xa inhibitor group have more advantages, the key ones being: substantial reductions in specific nutrition limitations and drug interaction, no need for routine laboratory monitoring and greatly improved therapy predictability. Rivaroxaban, a selective peroral Factor Xa inhibitor is more effective compared with enoxaparin for venous thromboembolism (VTE) prophylaxis in major orthopedic interventions. Though several single trials demonstrated no difference in hemorrhagic complications, certain meta-analyses with rivaroxaban showed a higher incidence of hemorrhage. Apixaban, a peroral reversible inhibitor of factor Xa approved for the prevention of VTE, compared with European-approved doses of enoxaparin has the efficacy almost equal to the North-American-approved enoxaparin doses without a significant difference in bleeding rates, though ?DVANCE I study points towards lower bleeding rates in patients treated with apixaban. To clarify the contradictory results of the recent meta-analysis related to the comparison between the stated factor X inhibitors and various comparator enoxaparin regimens as well as related to the risk for symptomatic PTE and total bleeding events following major orthopedic surgery, new research will be required. Specificities of rivaroxaban and apixaban, already constituting, according to modern recommendations, an integral part of the VTE prophylaxis protocols after major orthopedic interventions, will enable the establishment of personalized protocols aimed at developing an improved safety profile of each individual patient.

Application of a new type of metal clip hemostat in bleeding under endoscopic colonic polypectomy

Objective To analyze the effect of a new type of metal clip hemostat in bleeding under endoscopic colonic polypectomy. Methods From January 2016 to December 2017, 298 cases of colonic polypectomy hemorrhage patients in the Third People's Hospital of Hangzhou were studied, and they were randomly divided into study group (149 cases) and control group (149 cases) according to the digital table.The control group was given general hemostat and hemostatics, and the study group was given new metal clips and hemostatic drugs under endoscopy.The hemostasis rate, the prognosis in the near and long term and the score of the severity of clinical symptoms at different treatment time points (T0-before treatment, T1-12h after treatment, T2-24h after treatment and T3-48h after treatment) were compared and analyzed in the two groups. Results The immediate hemostasis rate (86.58%), effective hemostasis rate (73.15%) and complete hemostasis rate (66.44%) in the control group were significantly lower than those in the study group (100.00%, 93.29% and 89.93%), and there were statistically significant differences in bleeding rates between the two groups (χ2=21.439, 21.629, 24.104, all P 0.05). The scores of clinical symptoms of the two groups at T1, T2 and T3 were decreased in turn, and the scores in the study group were all lower than those in the control group(t=77.562, 54.816, all P<0.05). Conclusion After bleeding in patients with colonic polyp electrotomy, the hemostatic rate of the new metal clip after endoscopic hemostasis is significantly improved, the curative effect is stable, the recurrence rate of bleeding is low, and the clinical application value is high. Key words: Colonic polyps; Colonoscopy; Endoscopic mucosal resection; Bleeding; Metal clips; Hemostasis