Total Bleeding Events Research Articles

Impact of ticagrelor with or without aspirin on total and recurrent bleeding and ischemic events after percutaneous coronary intervention: A sub-study of the TWILIGHT trial.

In standard time-to-first event analysis, early aspirin discontinuation followed by ticagrelor monotherapy has been shown to reduce bleeding without increasing ischemic complications compared with ticagrelor plus aspirin after percutaneous coronary intervention (PCI). We evaluated whether these treatment effects are preserved when recurrent events are considered. In this TWILIGHT trial post hoc analysis, we assessed the effects of ticagrelor monotherapy on the total number of events that occurred over the 12-month follow-up among 7 119 high-risk patients randomized to aspirin or placebo in addition to ticagrelor at 3 months post-PCI if event-free and adherent to treatment. There were 391 patients with at least one Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (primary endpoint). Of those, 28 (7.2%) had a recurrent event. The total number of BARC 2, 3, or 5 bleeding events were 148 in the ticagrelor monotherapy arm compared with 278 with ticagrelor plus aspirin arm (p<0.001). Among 272 patients with at least one key secondary ischemic endpoint (all-cause death, myocardial infarction, or stroke), 37 (13.6%) sustained a recurrent event. Total ischemic events were similar (155vs 159) in the two groups. Among selected high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy followed by ticagrelor with or without aspirin, recurrent bleeding was less common than recurrent ischemic events over 12 months. Analysis of total events indicates that ticagrelor monotherapy continues to be more effective than ticagrelor plus aspirin in reducing bleeding without a signal of ischemic harm.

Multicenter retrospective cohort study demonstrates superior safety profile of indobufen over aspirin for Post-CABG antiplatelet therapy.

Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients' post-CABG. This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG.

Low-Intensity Heparin Infusion Compared With High-Intensity Heparin Infusion Dosing in Patients With Mechanical Mitral Valves: A Retrospective Cohort Study.

Patients with a mechanical mitral valve have an increased risk of thrombosis, and guidelines recommend a higher international normalized ratio goal for vitamin K antagonists-based anticoagulation. Guidelines provide recommendations for bridging with unfractionated heparin; however, there is no clear guidance on the heparin infusion intensity that should be used. This study was a retrospective, single-center, cohort study of patients aged ≥18 years or older with a mechanical mitral valve admitted from June 2019 to September 2022 who were maintained on a singular heparin infusion intensity nomogram for at least 48 hours. The patients were stratified into either a low- or a high-intensity heparin infusion nomogram. The exclusion criteria included non-nomogram heparin infusions and patients within 30 days of valve implantation. The primary outcome of this study was a composite of all bleeding events (major, clinically significant nonmajor, and minor bleeding). The secondary outcomes included bleeding events, analyzed individually, and thrombotic events. Seven total bleeding events were observed between the 2 groups, with 1 minor bleeding event in the low-intensity group and 6 bleeding events in the high-intensity group. One thrombotic event occurred in the high-intensity group. No statistically significant differences were found between the primary and secondary outcomes. Future studies are necessary to guide heparin infusion intensity selection in patients with mechanical mitral valves.

Thrombocytopenia and Adverse Bleeding Events in Neonatal Lumbar Punctures in the Emergency Department.

Lumbar punctures are performed as part of a routine evaluation of neonates with fever in the emergency department. Current recommendations regarding performing a lumbar puncture in the presence of thrombocytopenia exist for children with leukemia and other cancers; however, there are no such recommendations for the general neonatal population. This study assesses the frequency of thrombocytopenia and adverse bleeding events in neonates who undergo a lumbar puncture to determine whether a complete blood count, and specifically the platelet count, should be reviewed before performing the lumbar puncture. This is a retrospective chart review of neonates 30 days or younger presenting to a single freestanding pediatric emergency department who received a lumbar puncture over the course of 11 years. The complete blood count was reviewed for thrombocytopenia, determined to be platelet count of less than 150,000/μL. The chart was reviewed for any documented adverse bleeding events associated with the lumbar puncture. A total population of 2145 was studied with 56 patients determined to be thrombocytopenic. Seven total bleeding events were identified: 1 in the thrombocytopenic group and 6 in the nonthrombocytopenic group. All bleeding events were deemed to be clinically significant, either resulting in prolonged hospital stay or required further workup and medical intervention. The percentage of clinically adverse bleeding events that were related to the lumbar puncture was 0 (0.0%; 95% confidence interval, 0.0%-6.4%) and 2 (0.1%; 95% confidence interval, 0.0%-0.3%) ( P = 1.0) in the thrombocytopenic and nonthrombocytopenic groups, respectively. Our results demonstrated a very low risk of bleeding events associated with lumbar punctures in neonates, with no increased risk in the thrombocytopenic group. As such, we conclude that waiting for the results of a complete blood count before performing the lumbar puncture in neonates without a known bleeding disorder is unnecessary.

Von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease

AbstractLong-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in patients with von Willebrand disease (VWD) who have a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, noncontrolled, international phase 3 trial, investigated the efficacy and safety of Wilate prophylaxis in severe patients with VWD. Male and female patients 6 years or older with VWD types 1, 2 (except 2N), or 3 who had completed a prospective, 6-month, on-demand, run-in study (WIL-29) were eligible to receive Wilate prophylaxis for 12 months. At baseline, patients (n = 33) had a median age of 18 years. Six (18%) patients had severe type 1, 5 (15%) had type 2, and 22 (67%) had type 3 VWD. The primary end point of a >50% reduction in mean total annualized bleeding rate (TABR) with Wilate prophylaxis vs prior on-demand treatment was met; mean TABR during prophylaxis was 5.2, representing an 84.4% reduction. The bleeding reduction was consistent across age, sex, and VWD types. The mean spontaneous ABR was 3.2, representing an 86.9% reduction vs on-demand treatment. During prophylaxis, 10 (30.3%) patients had 0 bleeding events and 15 (45.5%) patients had 0 spontaneous bleeding events. Of 173 BEs, 84.4% were minor and 69.9% treated. No serious adverse events related to study treatment and no thrombotic events were recorded. Overall, WIL-31 showed that Wilate prophylaxis was efficacious and well-tolerated in pediatric and adult patients with VWD of all types. The WIL-29 and WIL-31 trials were registered at www.ClinicalTrials.gov as #NCT04053699 and #NCT04052698, respectively.

Resectability of Small Duodenal Tumors: A Randomized Controlled Trial Comparing Underwater Endoscopic Mucosal Resection and Cold Snare Polypectomy.

Underwater endoscopic mucosal resection (UEMR) and cold snare polypectomy (CSP) are novel endoscopic procedures for superficial nonampullary duodenal epithelial tumors (SNADET). However, consensus on how to use both procedures appropriately has not been established. In this study, we evaluated treatment outcomes of both procedures, including resectability. In this single-center randomized controlled study conducted between January 2020 and June 2022, patients with SNADET ≤12 mm were randomly allocated to UEMR and CSP groups. The primary end point was sufficient vertical R0 resection (SVR0), which was defined as R0 resection including a sufficient submucosal layer. We compared treatment outcomes including SVR0 rate between groups. The SVR0 rate was significantly higher in the UEMR group than in the CSP group (65.6% vs 41.5%, P = 0.01). By contrast, the R0 resection rate was not significantly different between study groups (70.3% vs 61.5%, P = 0.29). The submucosal layer thickness was significantly greater in the UEMR group than in the CSP group (median 546 [range, 309-833] μm vs 69 [0-295] μm, P < 0.01). CSP had a shorter total procedure time (median 12 [range, 8-16] min vs 1 [1-3] min, P < 0.01) and fewer total bleeding events (9.4% vs 1.5%, P = 0.06). UEMR has superior vertical resectability compared with CSP, but CSP has a shorter procedure time and fewer bleeding events. Although CSP is preferable for most small SNADET, UEMR should be selected for lesions that cannot be definitively diagnosed as mucosal low-grade neoplasias.

Management of Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer: A Systematic Review and Meta-Analysis

Background: Patients with cancer commonly require a central venous catheter (CVC) for delivery of cancer therapies and/or supportive care. The presence of a CVC is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding complications in patients with cancer and catheter-related upper extremity DVT. Methods: We searched MEDLINE, Embase, Scopus, and CENTRAL (Cochrane) from inception to June 2, 2023. We aimed to include randomized controlled trials (RCTs) (if any), prospective and retrospective cohort studies, and case-control studies (including ≥ 10 patients) evaluating adult patients with cancer and catheter-related upper extremity DVT. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates (with 95% confidence interval [CI]) of recurrent VTE and bleeding outcomes at different time points were pooled using random effects model. Results: After screening 4,264 records, we included 29 studies (N=2,848 patients) in the systematic review. There were no RCTs, 5 prospective cohort studies (including 260 patients), and 24 retrospective cohort studies. Most studies had modest sample size (N&amp;lt;100). Overall from 24 studies with reported tumor types, the most common malignancy was hematological malignancy (50.4%), followed by gastrointestinal (13.6%), breast (10.2%), and lung (5.5%) cancers. The median or mean follow-up duration varied widely from 1 to 20 months. Duration of anticoagulation also varied considerably with median or mean duration of 20 days to 6 months. The main long-term anticoagulant used was low-molecular-weight heparin (58.1%), followed by direct oral anticoagulants (24.3%). Only two studies (N=87 patients) specifically reported the management and associated outcomes after catheter removal. Thirteen studies (N=1105 patients) reported a 3-month recurrent VTE rate, with the pooled rate of 1% (95% CI 0-3%, I 2 = 0%) (Figure 1). Nine studies (N=811 patients) reported a 3-month major bleeding rate, with the pooled rate of 2% (95% CI 1-5%, I 2 = 0%) (Figure 2). We were unable to pool event rates beyond 3 months given high degree of heterogeneity in the follow-up duration, bleeding definition, and duration of anticoagulation. Conclusions: Our systematic review and meta-analysis demonstrated relatively low rates of recurrent VTE and major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months, and available data are poor to guide treatment strategies and duration of anticoagulation. The optimal management after catheter removal was also unclear. Future large prospective studies are needed.

Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular Heparin in Preventing Venous Thromboembolism in Inpatient Cancer Patients.

There are few studies on using rivaroxaban and low molecular heparin (LMWH) to prevent venous thromboembolism (VTE) in hospitalized cancer patients. We conducted a retrospective study to evaluate the efficacy and safety of rivaroxaban versus LMWH for the primary prevention of VTE in inpatient cancer patients. Information on patients was collected through 6-month follow-up and medical record inquiries. Clinical outcomes included VTE, total bleeding, thrombosis, major bleeding, minor bleeding, all-cause death, and a composite endpoint of bleeding, thrombosis, and death. A total of 602 hospitalized cancer patients were included in this study. During 6 months of follow-up, there were 26 VTE events (8.6%), 42 total bleeding events (7.0%), 62 all-cause deaths (10.3%), and 140 composite endpoints (23.3%). After adjusting for various confounding factors, there were no significant differences between the rivaroxaban and LMWH for VTE events (OR = 0.851, 95% CI [0.387-1.872], P=0.688), total bleeding (OR = 1.690, 95% CI [0.768-3.719], P = 0.192], thrombosis events (OR = 0.919, 95% CI [0.520-1.624], P = 0.772], major bleeding (OR = 0.276, 95% CI [0.037-2.059], P = 0.209), all-cause death (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), and composite endpoints (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), while minor bleeding (OR = 3.661 95% CI [1.000-7.083], P = 0.050) was significantly higher in the rivaroxaban than in the LMWH. In thromboprophylaxis in inpatient cancer patients, rivaroxaban has a similar rate of VTE and bleeding events as LMWH. Our results may provide a reference for the clinical use of rivaroxaban to prevent VTE in hospitalized cancer patients.

A Comparative Study on Ticagrelor and Clopidogrel in Patients With Acute Coronary Syndrome Treated With Primary Percutaneous Coronary Intervention.

To compare the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome (ACS) treated with primary percutaneous coronary intervention (PPCI). 3,528 consecutive patients with ACS treated with PPCI were divided into the ticagrelor and clopidogrel groups based on their dual antiplatelet therapy regimen at hospital discharge. Patient follow-up visits were completed 1, 6, and 12 months after PPCI treatment. Major adverse cardiac events (MACEs) and Bleeding Academic Research Consortium (BARC) bleeding events were assessed in both groups. In total, 2,501 cases were included in the ticagrelor group, and 817 cases were included in the clopidogrel group. The incidence of MACEs was lower in the ticagrelor group than in the clopidogrel group (P < 0.05). Ticagrelor group had lower incidence of all-cause death and cardiac death compared with clopidogrel group, the difference was significant (P<0.05). The incidences of study endpoints, including recurrent myocardial infarction and repeat revascularization, were not significantly different between the groups (P > 0.05). The incidences of BARC total and major bleeding events were not significantly different between the groups (P > 0.05). However, the incidences of BARC Types 1 and 2 bleeding events were lower in the ticagrelor group than in the clopidogrel group (P < 0.05). The multivariate COX regression analysis suggested that ticagrelor could decrease all-cause death compared with clopidogrel (P = 0.021).In patients with ACS treated with PPCI, ticagrelor could significantly reduce the risk of MACEs compared with clopidogrel, without increasing the risk of bleeding. This article is protected by copyright. All rights reserved.

Early mortality in acute myeloid leukemia with KMT2A rearrangement is associated with high risk of bleeding and disseminated intravascular coagulation.

Acute myeloid leukemia (AML) with rearrangement of lysine methyltransferase 2a gene (KMT2Ar) is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well-defined in this entity. In a retrospective analysis, causes and rates of early mortality following induction treatment were compared between a cohort of adults with KMT2Ar AML (N=172) and an age-matched cohort of patients with normal karyotype AML (N=522). The 60-day mortality in patients with KMT2Ar AML was 15% compared with 7% with normal karyotype (p=.04). We found a significantly higher occurrence of major bleeding events (p=.005) and total bleeding events (p=.001) in KMT2Ar AML compared with diploid AML. Among evaluable patients with KMT2Ar AML, 93% exhibited overt disseminated intravascular coagulopathy compared with 54% of patients with a normal karyotype before death (p=.03). In a multivariate analysis, KMT2Ar and a monocytic phenotypic were the only independent predictors of any bleeding event in patients who died within 60days (odds ratio, 3.5; 95% CI, 1.4-10.4; p= .03; odds ratio, 3.2; 95% CI, 1-1-9.4; p= .04, respectively). In conclusion, early recognition and aggressive management of disseminated intravascular coagulopathy and coagulopathy are important considerations that could mitigate the risk of death during induction treatment in KMT2Ar AML. Acute myeloid leukemia (AML) with rearrangement of KMT2A is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well-defined in this entity. In this article, that KMT2A-rearranged AML is demonstrably associated with higher early mortality and an increased risk of bleeding and coagulopathy, specifically, disseminated intravascular coagulation, compared with normal karyotype AML. These findings emphasize the importance of monitoring and mitigating coagulopathy in KMT2A-rearranged leukemia similar to what is done in acute promyelocytic leukemia.

Efficacy and Safety of Rivaroxaban and Enoxaparin for Thromboprophylaxis Among Total Hip Arthroplasty Patients: A Systematic Review and Meta-Analysis.

Venous thromboembolism (VTE) is one of the major and potentially life-threatening complications following major orthopedic surgeries. Research evidence comparing the effectiveness of rivaroxaban and enoxaparin for thromboprophylaxis specific to total hip arthroplasty (THA) has been limited. Hence, this review was done to compare the efficacy and safety of rivaroxaban against enoxaparin for thromboprophylaxis after THA. We conducted a search in databases including Medline, EMBASE, ScienceDirect, Google Scholar, and Cochrane Library from inception until May 2021. Randomized controlled trials directly comparing the effectiveness of rivaroxaban and enoxaparin for thromboprophylaxis among patients undergoing THA were eligible for inclusion. Outcome parameters assessed were efficacy in terms of total VTE and all-cause mortality, major VTE, deep vein thrombosis, symptomatic VTE, and safety in terms of major bleeding events, clinically relevant nonmajor bleeding events, minor bleeding events, total bleeding events, drug-related adverse events, and wound infection. We performed a meta-analysis with a random effects model and reported a pooled risk ratio (RR) with a 95% confidence interval (CI). Eleven studies, including 9057 participants, were analyzed. Amongst efficacy outcomes, VTE and all-cause mortality pooled an RR of 0.58 (95% CI: 0.34-0.99), major VTE pooled an RR of 0.37 (95% CI: 0.15-0.90), deep vein thrombosis pooled an RR of 0.57 (95% CI: 0.32-1.02), and symptomatic VTE pooled an RR of 0.51 (95% CI: 0.30-0.87). Amongst safety outcomes, major bleeding events pooled an RR of 1.18 (95% CI: 0.77-1.80), total bleeding events pooled an RR of 1.12 (95% CI: 0.93-1.34), drug-related adverse event pooled an RR of 0.99 (95% CI: 0.87-1.12), and wound infection pooled an RR of 1.11 (95% CI: 0.58-2.14). Rivaroxaban is a more efficacious drug in terms of VTE and all-cause mortality compared to enoxaparin following THA, and rivaroxaban was non-inferior in terms of safety profiles such as wound infection, bleeding, and drug-related adverse events.

Pharmacogenetics of warfarin dosing in Chinese adults with nonvalvular atrial fibrillation.

The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fibrillation (AF) is still lacking. We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients. Our study consisted of 508 newly recruited and 471 existing Chinese AF patients. Among the total 979 patients, 585 patients received their dose of warfarin determined by a genetic and clinical factor (gene group), while the remaining 394 patients whose dosing was determined empirically in control group. We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR during 12-month follow-up. Secondary safety outcome included bleeding and thrombotic events. Compared with the control group, the average TTR of the gene group was higher [68.4 ± 20.6% vs 48.5 ± 21.6%, P < 0.001]. The average INR monitoring times to reach the therapeutic time in the gene group was lower (P < 0.001). The risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding, and intracerebral bleeding events were not significantly different between the two groups (P > 0.05). Comparing to the analysis using existing 471 patients, the analysis using total 979 patients showed that the gene group experienced a lower (RR 0.4 (95% CI 0.2 to 0.8), P = 0.008) incidence of cumulative ischemic stroke. Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

Impact of the Japanese Version of High Bleeding Risk Criteria on Clinical Outcomes in Patients with ST-segment Elevation Myocardial Infarction.

Bleeding complications are often observed in patients with ST-segment elevation myocardial infarction (STEMI). Although the Japanese version of the high bleeding risk criteria (J-HBR) were established, it has not been sufficiently validated in patients with STEMI. This retrospective study aims to examine whether J-HBR is associated with cardiovascular and bleeding events in patients with STEMI. We included 897 patients with STEMI and divided them into the J-HBR group (n=567) and the non-J-HBR group (n=330). The primary endpoint was the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction, ischemic stroke, and systemic embolism. Another primary endpoint was total bleeding events defined as type 3 or 5 bleeding events as defined by the Bleeding Academic Research Consortium . During the median follow-up duration of 573 days, 187 MACE and 141 total bleeding events were observed. The Kaplan-Meier curves showed that MACE and total bleeding events were more frequently observed in the J-HBR group than in the non-J-HBR group (p＜0.001). Multivariate Cox hazard analysis revealed that after controlling for multiple confounding factors, the J-HBR group was significantly associated with MACE (hazard ratio [HR] 4.676, 95% confidence interval (CI) 2.936-7.448, p＜0.001) and total bleeding events (HR 6.325, 95% CI 3.376-11.851, p＜0.001). J-HBR is significantly associated with MACE and total bleeding events in patients with STEMI. This study validated J-HBR as a risk marker for bleeding events and suggests J-HBR as a potential risk marker for MACE in patients with STEMI.

Management of Anticoagulation and Related Outcomes in Patients with Cancer-Associated Thrombosis and Thrombocytopenia: A Systematic Review and Meta-Analysis

Background: Patients with cancer have an increased risk of venous thromboembolism (VTE) requiring anticoagulation, as well as an increased risk of thrombocytopenia due to cancer therapies or cancer itself. The optimal management of patients with VTE and thrombocytopenia is unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and major bleeding in patients with cancer associated thrombosis and thrombocytopenia according to different anticoagulation management strategies. Methods: We searched MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials from inception to February 5, 2022. Studies assessing adult patients with cancer associated thrombosis and thrombocytopenia (platelet count < 100 x 109/L) due to malignancy or cancer therapy were included. Three main anticoagulation management strategies were reported: full dose (therapeutic dose anticoagulation +/- platelet transfusion support), modified dose (including 50% dose, prophylactic dose, or shortened duration of anticoagulation), or no anticoagulant. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates of thrombotic and bleeding outcomes by anticoagulation management strategies were pooled using random effects model and expressed as events per 100 patient-months with associated 95% confidence intervals (CI). The quality of studies was assessed by ROBINS-I tool. Results: After screening 4,341 records, we included 19 studies (N=1,728 patients with platelet count < 100 x 109/L) in the systematic review, 12 of which were included in the meta-analysis (N=790) (Figure 1). There were no RCTs, two prospective cohort studies, and the rest were retrospective cohort studies. Most studies were small (N=13-471) and limited to patients with platelet count < 50 x 109/L. The majority (~90%) of patients had hematological malignancies or stem cell transplant. Low-molecular-weight heparin was the main anticoagulant reported. All studies were judged to have serious risk of bias, mainly from bias due to confounding and bias due to deviations from intended interventions. The rates of recurrent VTE, major bleeding, and total bleeding events stratified by anticoagulation management strategies (full dose, modified dose, no anticoagulation) were summarized in Table 1. The rates of recurrent VTE and bleeding complications were high regardless of the management strategies - recurrent VTE on full dose anticoagulant: 2.97 per 100 patient-months (95% confidence interval [CI] 1.86-4.75), modified dose: 7.32 per 100 patient-months (95% CI 3.59-14.94); major bleeding on full dose: 4.36 per 100 patient-months (95% CI 2.53-7.50), modified dose: 4.34 per 100 patient-months (2.30-8.20) (Table 1). There was high degree of heterogeneity in the patient population included, acuity and type of VTE, bleeding criteria used, and follow-up durations. Most studies did not account for the differences in baseline characteristics when outcomes associated with different anticoagulation strategies were reported and analyzed, which could influence the results. Conclusions: Patients with cancer associated thrombosis and thrombocytopenia have high risks of both recurrent VTE and major bleeding. Our systematic review and meta-analysis demonstrated significant heterogeneity in study conduct and reporting. Our ability to draw a firm conclusion to guide management from the current literature is severely hindered by this limitation. RCTs are needed to define the optimal care for this high-risk population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcome of anticoagulation with rivaroxaban in patients with non-retrieved inferior vena cava filters for the prevention of filter thrombosis: a retrospective cohort study

BackgroundNon-retrieved inferior vena cava filter (IVCF) is associated with some severe complications, such as filter thrombosis. The aim of this retrospective cohort study was to evaluate the outcome of rivaroxaban for the prevention of filter thrombosis in patients with non-retrieved IVCF.MethodsThe study based on the VTE registry databases was limited to patients with non-retrieved IVCF treated at Nanjing Drum Tower Hospital from January 2012 to December 2017. Outcomes included filter thrombosis, total bleeding events, death.ResultsA total of 202 patients were enrolled in the study and divided into rivaroxaban group and warfarin group. Mean follow-up period of the two groups was 57.4 ± 20.8 and 62.2 ± 23.0 months, respectively. In risk factors for VTE, transient factors (P = 0.008) and history of VTE (P = 0.028) were statistically different between the two groups. A total of 13 (6.4%) patients developed filter complications, of which 4 (3.5%) and 5 (5.7%) patients in rivaroxaban group and warfarin group developed filter thrombosis, respectively, without significant difference (P = 0.690). The total bleeding events in rivaroxaban group, including major bleeding and clinically relevant and non-major (CRNM) bleeding, were significantly lower than that in warfarin group (P = 0.005). Adjusting for hypertension, transient risk factors, history of VTE and cancer, no differences in the hazard ratio for outcomes were notable.ConclusionsIt is necessary to perform a concomitant anticoagulation in patients with non-retrieved filters. Rivaroxaban can be an alternative anticoagulant option for the prevention of filter thrombosis.

Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease

Appropriate regimens of antithrombotic therapy for patients with atrial fibrillation (AF) and coronary artery disease (CAD) have not yet been established. To compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and combined rivaroxaban and antiplatelet therapy in such patients. This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label, randomized clinical trial. This multicenter analysis was conducted from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. Data were analyzed from September 1, 2020, to March 26, 2021. Rivaroxaban monotherapy or combined rivaroxaban and antiplatelet therapy. The total incidence of thrombotic, bleeding, and fatal events was compared between the groups. Cox regression analyses were used to estimate the risk of subsequent events in the 2 groups, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable. A total of 2215 patients (mean [SD] age, 74 [8.2] years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis. The total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108), respectively, during a median follow-up of 24.1 (IQR, 17.3-31.5) months. The mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group. Rivaroxaban monotherapy was associated with a lower risk of total events compared with combination therapy (hazard ratio, 0.62; 95% CI, 0.48-0.80; P < .001). Monotherapy was an independent factor associated with a lower risk of subsequent events compared with combination therapy. The mortality risk after a bleeding event (monotherapy, 75% [6 of 8]; combination therapy, 62.1% [18 of 29]) was higher than that after a thrombotic event (monotherapy, 25% [2 of 8]; combination therapy, 37.9% [11 of 29]). Rivaroxaban monotherapy was associated with lower risks of total thrombotic and/or bleeding events than combination therapy in patients with AF and stable CAD. Tapered antithrombotic therapy with a sole anticoagulant should be considered in these patients. ClinicalTrials.gov Identifier: NCT02642419.

Safety and efficacy of non-vitamin K antagonist oral anticoagulants compared with well-controlled warfarin in Thai patients with atrial fibrillation.

In trials of patients with atrial fibrillation (AF), non-vitamin K antagonist oral anticoagulants (NOACs) were not inferior to warfarin for thromboembolic and bleeding events. However, there are scant data comparing the efficacy and safety of NOACs in patients with AF with that of well-controlled warfarin treatment in such patients. To compare total bleeding and thromboembolic events in patients with AF who received NOACs, with the same events in those who received well-controlled warfarin treatment. We used retrospective data from patients with AF who received NOACs or well-controlled warfarin at the Central Chest Institute of Thailand from January 2017 to December 2019. The primary outcome was total bleeding or thromboembolic events or both. The secondary outcome was all-cause mortality, total bleeding events including major or minor bleeding, and thromboembolic events including ischemic stroke or systemic embolization. We included data from 180 patients with AF, 90 who received NOACs and 90 who received well-controlled warfarin. The average time in the therapeutic range for those who received warfarin was 84.9% ± 9.8%. The patients who received well-controlled warfarin had more frequent thromboembolic or total bleeding events or both than those who received NOACs (odds ratio [OR] 3.17; 95% confidence interval [CI] 2.27-4.07; P = 0.01). There were more minor bleeding events in those who received well-controlled warfarin (OR 3.75; 95% CI 2.79-4.71; P = 0.01). However, there was no significant difference in thromboembolic events, major bleeding, or all-cause mortality between the 2 groups. Thai patients with AF who received NOACs had less thromboembolic or total bleeding events than those who received well-controlled warfarin treatment.

Acute myeloid leukemia with KMT2Ar and association with risk of bleeding and early mortality.

7026 Background: Acute myeloid leukemia (AML) with rearrangement of KMT2A is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well-defined in this entity. Methods: In a retrospective analysis, we compared causes and rates of early mortality following induction treatment between a cohort of adults with KMT2Ar AML (N=172) and an age-matched cohort of patients (pts) with normal karyotype (NK) AML (N=522). Results: The 30 and 60-day (60d) mortality in pts with KMT2Ar AML were significantly higher compared to those with NK AML, with rates of 10% (17/172 pts) and 15% (26/172 pts) in KMT2Ar AML vs 4% (20/522 pts) and 7% (38/522 pts) in NK AML, respectively ( P=0.004). Among those who died within 60d, the most common contributing cause in KMT2Ar was respiratory failure without a clear infectious etiology in 38% (10/26 pts) vs 11% (4/38 pts) in NK AML ( P=0.01). We found 42% (11/26 pts) with KMT2Ar AML who died within 60d were either diagnosed with or had high clinical suspicion for diffuse alveolar hemorrhage (DAH) that warranted empiric therapy vs 18% (7/38 pts) with NK AML ( P=0.05). Given the high occurrence of DAH in KMT2Ar AML, we set out to quantify bleeding events and recorded major and minor bleeds as defined by the International Society of Thrombosis and Haemostasis. We found 65% (17/26 pts) with KMT2Ar AML had at least one bleeding event vs 32% (12/38 pts) with NK AML ( P=0.01). There was a significantly higher frequent occurrence of major bleeds (rate ratio=6.22; P=0.005) and total bleeding events (rate ratio=4.5; P=0.001) in KMT2Ar AML vs NK AML. KMT2Ar was associated with disseminated intravascular coagulopathy (DIC), as 93% of evaluable pts (14/15 pts) vs 54% (7/13 pts) in NK AML had overt DIC before death. Longitudinal trajectories of DIC parameters of pts who died within 60d showed significantly higher prothrombin time levels ( P=0.008) in KMT2Ar. In a multivariate analysis, KMT2Ar and a monocytic phenotypic were the only independent predictors of any bleeding event in pts who died within 60d (OR 3.5, 95% CI 1.4-10.4, P=0.03; OR 3.2, 95% CI 1.1-9.4, P=0.04). Conclusions: KMT2Ar AML is associated with higher early mortality and an increased risk of bleeding and coagulopathy compared with NK AML. Early recognition and aggressive management of DIC and coagulopathy are important considerations that could mitigate the risk of death during induction treatment.[Table: see text]

No effect of desmopressin administration before kidney biopsy on the risk of major post-biopsy bleeding

Background/AimsThe most important complication of kidney biopsy is bleeding, and it is unclear whether desmopressin is effective in preventing it. Thus, the study was conducted to compare post-biopsy bleeding with or without desmopressin prescription prior to percutaneous kidney biopsy. MethodsIn this single-centered, retrospective, and observational study, 3,018 adult patients who underwent kidney biopsy between January 1, 2003 and March 31, 2019 at our institute were recruited. Of these, 776 patients received desmopressin. To compare the differences in major bleeding events between patients administered and not administered with desmopressin, propensity score matching was performed. ResultsBefore propensity score (PS) matching, it was observed that patients in the desmopressin group were significantly older (p<0.001) and had a higher blood pressure (p<0.001), higher serum creatinine (p<0.001), lower hemoglobin levels (p<0.001), and lower platelet counts (p=0.001) than those in the no-desmopressin group. Furthermore, the incidence of renal artery embolization was not significantly different between the two groups (p=0.077); however, blood transfusions occurred significantly more frequently in the desmopressin group (p<0.001). A comparison of the two groups after PS matching did not reveal any differences in the incidence of renal artery embolization (p=0.341), blood transfusion (p=0.579), and total major bleeding events (p=0.442). Furthermore, there was no difference in the incidence of perinephric hematoma on computed tomography or ultrasound (p=0.120). ConclusionsWe do not recommend desmopressin administration before kidney biopsy.

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA

BackgroundComparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in CYP2C19 loss-of-function carriers have not been extensively performed.MethodsWe conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days.ResultsA total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P=0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively.ConclusionsAmong Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People’s Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.)