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Background: Atrial fibrillation (AF) poses significant thromboembolism and bleeding risks, especially in older adults. Warfarin continues to be a primary treatment option, and maintaining the Time in Therapeutic Range (TTR) is critical for ensuring its effectiveness. However, suboptimal TTR is associated with increased risks of stroke, bleeding, and mortality. Despite its importance, there is limited data on warfarin management in Ethiopian older adults with AF. Therefore, this study aimed to determine the TTR, bleeding events, and their determinants, in older patients with AF in Ethiopia receiving warfarin therapy. Method: In this study, older patients with AF who were treated with warfarin and had follow-up visits between May 2021 and May 2024, and met the inclusion criteria, were included. Patients were categorized based on TTR into two groups: poor anticoagulation (TTR < 65%) and good anticoagulation quality (TTR ≥ 65%). Bivariate and Multivariate Logistic regression was performed to predict determinants of a TTR < 65% and bleeding events. Odds ratios with 95% confidence intervals (CIs) were calculated, and statistical significance was set at P < 0.05. Results: In this study, 384 patients with AF were included. Of this 53.4% were female. Of these 71% of patients had a TTR below 65%, 29% achieved ≥65%, with a median TTR of 45%. Bleeding events were reported by 13.5% of patients. Poor TTR was significantly associated with age (AOR = 1.199, 95% CI: 1.109–1.297), chronic kidney disease (AOR = 27.809, 95% CI: 7.57–101.76), and infrequent INR monitoring at 31–90-day intervals (AOR = 0.15, 95% CI: 0.004–0.051). Regarding determinants of bleeding events, Patients with diabetes mellitus had a 2.6-fold higher bleeding risk (AOR = 2.585, 95% CI: 1.069–6.250), and a CHA2DS2-VASc score ≥3 significantly increased bleeding risk compared to scores ≤2 (AOR = 7.562, 95% CI: 2.770–20.640). Conclusion: This study highlights suboptimal warfarin therapy among older Ethiopian patients with AF. Poor anticoagulation was associated with advanced age, chronic kidney disease, and infrequent INR monitoring, while diabetes mellitus and high CHA₂DS₂-VASc scores increased bleeding risks. Close monitoring and frequent INR checks are essential to improving outcomes. [ABSTRACT FROM AUTHOR]

Background and purpose: Although Ginkgo biloba extract (GBE) has been shown to be effective in treating acute ischemic stroke (AIS) in several clinical trials, concerns regarding adverse events, such as bleeding, have been raised. This study aimed to investigate the mechanisms by which GBE improves AIS prognosis, particularly its impact on platelet activity, coagulation function, and the potential risk of bleeding. Methods: This real-world study consecutively enrolled 99 patients: 49 with internal jugular venous stenosis (IJVS) treated with GBE; 33 with AIS treated with GBE and low-dose aspirin; and 17 with AIS treated with low-dose aspirin alone. Plasma platelet aggregation and coagulation status were assessed before and after treatment. Major and minor bleeding events were recorded in the AIS group. Results: In the IJVS group, GBE specifically inhibited arachidonic acid (AA)-induced, but not ADP-induced, platelet aggregation, along with prolonged thrombin time (PT) and activated partial thromboplastin time (APTT). In the AIS group, the combined use of low-dose aspirin and GBE further reduced AA-induced platelet aggregation, mildly prolonged APTT, and was associated with an increased risk of minor bleeding events. Conclusions: The therapeutic effect of GBE in AIS may, in part, be attributed to its ability to enhance the antiplatelet action of aspirin, particularly in inhibiting AA-induced platelet aggregation. However, the potential for increased bleeding risk warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: The number of patients with hip and femoral fractures is increasing and is expected to further increase in upcoming years due to the ageing population and the life expectancy of the general population. In this analysis, we aimed to systematically assess the post-operative complications associated with the pre-operative use of Aspirin in patients undergoing surgery for hip or femoral fracture. Methods: Common online databases: Google Scholar, Web of Science, MEDLINE, Cochrane database, EMBASE (), and were searched for English-based studies which reported post-operative outcomes in patients with versus without the use of Aspirin prior to surgery for hip or femoral fracture. The endpoints of this analysis included cerebro-vascular attack, acute coronary syndrome/cardiovascular complications, hematoma, deep venous thrombosis, pulmonary embolism, patients requiring blood transfusion, bleeding events, and in-hospital mortality. RevMan software 5.4 was the statistical software used for this meta-analysis. Risk ratio (RR) with 95% confidence intervals (CI) was used to represent the post-analytical result. Results: A total number of 2823 participants were included in this analysis whereby 821 were assigned to Aspirin prior to surgery. Results of this analysis showed that post-operatively the risk of cerebrovascular attack (RR: 1.62, 95% CI 0.29–9.20; P = 0.58), cardiovascular complication (RR: 1.86, 95% CI 0.62–5.52; P = 0.27), pulmonary embolism (RR: 2.45, 95% CI 0.77–7.77; P = 0.13), bleeding events (RR: 1.24, 95% CI 0.39–3.96; P = 0.71), and in-hospital mortality (RR: 0.95, 95% CI 0.47–1.91; P = 0.89) were not significantly higher in those patients who were and who were not taking Aspirin pre-operatively. The risk of deep venous thrombosis (RR: 1.82, 95% CI 0.23–14.60; P = 0.57), hematoma formation (RR: 1.57, 95% CI 0.11–21.49; P = 0.74) and patients requiring blood transfusion post-operatively (RR: 1.22, 95% CI 0.99–1.52; P = 0.07) were not significantly different in patients who were on Aspirin and those who were not on Aspirin pre-operatively. Conclusion: The post-operative complications associated with the pre-operative use of Aspirin in patients undergoing surgery for hip or femoral fracture were apparently not significantly different when compared to patients who were not on Aspirin. Therefore, Aspirin should not be considered an absolute contraindication in patients undergoing surgery for hip or femoral fracture. Hence, an early or emergency surgery for hip or femoral neck fracture in patients on Aspirin therapy should apparently not pose any problem. Further larger trials should be able to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

OBJECTIVES The appropriate antithrombotic regimen after a Fontan operation is yet to be elucidated. Hence, this study aimed to compare the incidence of thromboembolic events in patients with and without receiving warfarin for thromboprophylaxis in a large post-Fontan population. METHODS This retrospective cohort study used data from the Diagnosis Procedure Combination database in Japan between April 2011 and March 2022. We identified all patients who underwent a Fontan operation and excluded those who were born before 2010, died during the hospitalization or received mechanical heart replacement. Propensity score overlap weighting was performed between patients discharged with warfarin (with or without aspirin) and the control group (only aspirin or neither aspirin nor warfarin). Cox and Fine-Gray hazards models compared thromboembolic and bleeding events. RESULTS We identified 2007 eligible patients, including 1670 warfarin users and 337 non-users. The mean follow-up duration was 2.1 years. The crude proportions of thromboembolic events were 3.0% and 3.0% and those of bleeding events were 0.4% and 0.3% in the warfarin and control groups, respectively. There was no significant difference in thromboembolic events between the groups (sub-distribution hazard ratio: 0.77; 95% confidence interval 0.39–1.51; P  = 0.45) or bleeding events (sub-distribution hazard ratio: 0.78; 95% confidence interval 0.09–7.03; P  = 0.83). CONCLUSIONS Warfarin use at discharge after a Fontan operation may not be necessary for thromboembolism prophylaxis in paediatric patients, based on large-scale real-world data, with a mean postoperative follow-up duration of 2.1 years. There is room for further studies to reconsider routine warfarin use in patients post-Fontan operation. [ABSTRACT FROM AUTHOR]

We report the first large-scale retrospective cohort study on adolescent and young adult (AYA) polycythemia vera (PV) and essential thrombocythemia (ET) in Japan, a subgroup analysis using Japanese multicenter registry data (JSH-MPN-R18). This study included patients with PV (n = 31) or ET (n = 141) aged 20 to 39 years at the initial visit. Hemorrhage-free survival (HFS) was better in AYA ET than in non-AYA ET (5-year HFS: 100% vs. 88.6%, p < 0.01), which might be attributed to differences in antithrombotic treatment rates between AYA and non-AYA patients. Although thrombosis-free survival did not differ statistically, the percentage of venous thrombotic events (TEs) among total TEs was higher in AYA compared to non-AYA PV and ET in Japan (26.0% vs. 6.0%, p < 0.01), but much lower than figures reported in European or US cohorts. Cytoreductive therapy (CRT) was administered to 25.8% of AYA patients with PV and 43.3% of AYA patients with ET, and the reason was usually unrelated to high risk of thrombosis. These results could be used to develop a more appropriate strategy for managing PV and ET in the Japanese AYA population. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy of a triple antithrombotic regimen (warfarin, aspirin, and clopidogrel) in patients with atrial fibrillation (AF) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) and investigate the factors influencing bleeding events in these patients after PCI. Methods Clinical data from 105 AF patients with CAD who received PCI from January 2020 to January 2022 were collected. Patients were divided into three groups based on their post-PCI antithrombotic regimen; the triple therapy group (37 cases on warfarin, aspirin, and clopidogrel), the AC group (35 cases on aspirin and clopidogrel), and the WC group (33 cases on warfarin and clopidogrel). Over a 12month follow up, coagulation parameters, including prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and fibrinogen (Fib), incidence of major adverse cardiovascular events (MACE), and bleeding events were compared across groups, and the factors influencing bleeding events were analyzed. Results Post-treatment, PT, TT, and APTT significantly increased, while Fib levels decreased in all groups (P<0.01); however, no significant differences were observed among the groups for PT, TT, APTT, or Fib values after treatment (P>0.05). The incidence of MACE was 2.7% in the triple therapy group, 17.1% in the AC group, and 18.2% in the WC group, with no significant difference between groups (P>0.05). In terms of bleeding events, no major bleeding occurred in the AC or WC groups; minor bleeding events occurred in 8.57% and 6.06% of cases, respectively. In the triple therapy group, the major bleeding rate was 5.41%, with minor bleeding at 13.51%, totaling 18.92%, with no significant difference between groups (x² = 2.906, P=0.231). Age and HAS - BLED scores were significantly different between the bleeding and non bleeding groups (P<0.05), with the bleeding group being older (76.76 ±3.47) years than the non bleeding group (59.62 ±3.33) years. Additionally, 100% of the bleeding group had a HAS - BLED score ≥3, compared to 31.1% in the non bleeding group (P<0.05). Logistic regression analysis, using age and HAS BLED scores as independent variables, indicated that age (OR = 1.085, 95% CI: 1.0041. 173, P=0.040) and HAS BLED score (OR =4.984, 95% CI: 1. 188-20.902, P=0.028) were independent risk factors for bleeding after PCI. Conclusion The triple antithrombotic therapy regimen of warfarin, aspirin, and clopidogrel can effectively improve hypercoagulability and reduce thrombotic risk in AF patients with CAD after PCL. Age and HAS - BLED score are independent risk factors for post-PCI bleeding events in these patients. Risk assessment is essential in choosing postoperative antithrombotic therapy to improve treatment safety. [ABSTRACT FROM AUTHOR]

Key Clinical Massage: Tubo‐ovarian abscess (TOA) is a serious health hazard for women, causing severe sepsis. Antimicrobial treatment is effective, but one‐third of patients experience unfavorable outcomes. ITP, an autoimmune condition, can lead to bruising and bleeding. Diagnosing TOA in women of childbearing age is crucial, and combining emergency surgery with ITP patients can increase treatment costs and reduce quality of life. ITP can lead to severe complications, including postoperative hemorrhage, and may require platelet transfusions, glucocorticosteroids, and immunoglobulin. These treatments increase costs, decrease quality of life, and impact prognosis. Preventing ITP is crucial. Patients should be administered blood products based on platelet count and anemia or spontaneous bleeding tendencies. Perioperative blood management should aim for a target platelet level of 30 × 109/L and a hemoglobin concentration of 80 g/L before surgery. Post‐surgery, perioperative care is crucial and vigilant for secondary bleeding. A tubo‐ovarian abscess (TOA) is a frequently encountered inflammatory mass in therapeutic settings. TOA is a serious consequence of pelvic inflammatory disease (PID) that can lead to severe sepsis. In recent years, the incidence of TOA has increased, presenting a significant health hazard for women. To effectively target the diverse range of bacteria responsible for TOA, it is essential to use antimicrobial medicines that have a wide spectrum of activity. Nevertheless, the efficacy of antibiotic treatment stands at approximately 70%, while a significant proportion of patients, around one‐third, experience unfavorable clinical outcomes necessitating drainage or surgical intervention. Immune thrombocytopenia (ITP) is an autoimmune condition characterized by a marked decrease in the quantity of platelets present in the bloodstream. ITP is characterized by thrombocytopenia, which leads to a heightened susceptibility to bruising and bleeding. The diagnosis of ITP and the prediction of treatment response continue to pose important and persistent issues in the field of hematology. The platelet count is commonly employed as a surrogate indicator of disease severity in patients with ITP and thus plays a crucial role in determining the necessity of treatment. A 25‐year‐old woman with a history of sexual activity underwent open abdominal exploration due to the sudden onset of lower abdominal pain. During the operation, a left TOA was discovered, and an incision and drainage were performed. Symptomatic treatments, such as anti‐infectives and abdominal drainage, were administered. The culture of pus in the abdominal cavity suggested the presence of Escherichia coli. However, the patient presented with ITP and had a platelet count of less than 50 × 109/L before the operation. After the operation, the patient developed incisional and pelvic hematomas with signs of infection. As a result, the patient was discharged from the hospital after undergoing another laparotomy and receiving platelet transfusions and immunotherapy. Clinicians should be vigilant when diagnosing TOA in women of childbearing age, even in the absence of high‐risk factors. A timely antibiotic or surgical intervention is necessary to preserve fertility and ensure quality of life. Combining emergency surgery with ITP patients poses a significant challenge for clinicians in terms of treatment. ITP can lead to serious complications, such as postoperative bleeding, which may require platelet transfusions, glucocorticoids, and immunoglobulin. This can increase the cost of treatment, reduce the quality of life, and seriously affect the prognosis. Therefore, preventing ITP is crucial. It is important to pay attention to the perioperative care of patients after surgery and be alert to the possibility of secondary hemorrhage. [ABSTRACT FROM AUTHOR]

We investigated bleeding complications in patients admitted to the emergency department (ED) who were taking oral anticoagulants and compared the rates of major and minor bleeding events between the direct oral anticoagulant (DOAC) and warfarin groups. We conducted a prospective, multicenter observational study of warfarinand DOAC-treated patients who presented to the EDs of tertiary-care hospitals between July 2020 and July 2021 with a bleeding event. Among 518 patients on anticoagulation therapy, 121 (23.4%) presented to EDs with bleeding events. A chart review revealed 73 (60.24%) patients with bleeding events who were taking a DOAC (i.e., apixaban, edoxaban, rivaroxaban, or dabigatran) and 48 who were taking warfarin. The rate of bleeding events was significantly higher among patients treated with warfarin than among those treated with DOACs (48/129 [37.2%] vs. 73/389 [18.8%], p<0,001). Subgroup analysis of the DOAC-treated patients revealed a significant difference in the frequency of bleeding events among the DOAC groups (p=0.016), with a significantly lower frequency in patients treated with rivaroxaban versus edoxaban (14.9% vs. 34.7%, p=0.002) and in those treated with apixaban versus edoxaban (18.8% vs. 34.7%, p=0.021). Our findings indicate that although the rates of overall bleeding events differed among DOAC-treated patients, the rates of bleeding events were lower than those in warfarin-treated patients. Additionally, major bleeding events occurred less frequently in patients treated with rivaroxaban or apixaban compared with edoxaban. [ABSTRACT FROM AUTHOR]

Background: Percutaneous (PC) access has become the first‐line strategy for transfemoral (TF) transcatheter aortic valve replacement (TAVR), but surgical cutdown (SC) may be required in selected and usually challenging cases. We aimed to compare the efficacy and safety of SC versus echo‐guided PC approach in TF TAVR. Methods: Between November 2019 and December 2020, all patients undergoing TF TAVR were included in a prospective study. The choice of PC or SC strategy was left at operators' discretion, according to predictable access site difficulties. The primary endpoint included all vascular complications (VCs) and all bleeding at 1‐month follow‐up according to Valve Academic Research Consortium‐2 criteria. Results: Among 225 patients, 166 (73.8%) and 59 (26.2%) underwent PC or SC approach, respectively. Median age was 82 years, EuroSCORE 2 was higher (p = 0.02), and peripheral arterial disease (p < 0.001) was more common in the SC group. Femoral access was successful in 100% in the SC group vs 97.6% in the PC group (p = 0.2). The primary endpoint was reached in 32 patients (14.2%), 5 (8.4%) in the SC group and 27 (16.2%) in the PC group (p = 0.1) with low incidence of major VC in both groups (1.7% vs 3% in the SC and PC groups respectively, p = 0.6). Conclusion: Despite a higher risk profile of patients in the SC group, SC and PC approaches appear safe and effective in TF TAVR, with a high success rate. SC may be considered when vascular access is anticipated as complex, but this strategy might be confirmed in a randomized study. Trial Registration: ClinicalTrials.gov identifier: NCT03865043 [ABSTRACT FROM AUTHOR]

Background: Interventional left atrial appendage occlusion (LAAO) mitigates the risk of thromboembolic events in nonvalvular atrial fibrillation (AF) patients with contraindication for long-term oral anticoagulation (OAC). Patients with prior stroke have a relevantly increased risk of recurrent stroke, so the effectiveness of LAAO could be reduced in this specific very high-risk patient group. Aim: This sub-study of the LAARGE registry investigates the effectiveness and safety of LAAO for secondary prevention in nonvalvular AF patients with a history of stroke. Methods: LAARGE is a prospective, non-randomised registry on the clinical reality of LAAO. The current sub-study employs data from index procedure and 1-year follow-up. Effectiveness and safety were assessed by documentation of all-cause mortality, non-fatal thromboembolism, procedure-related complications, and bleeding events. Results: A total of 638 patients were consecutively included from 38 hospitals in Germany and divided into two groups: 137 patients with a history of stroke (21.5%) and 501 patients without. Successful implantation was consistent between both groups (98.5% vs. 97.4%, p = NS), while peri-procedural MACCE and other complications were rare (0% vs. 0.6% and 4.4% vs. 4.0%, respectively; each p = NS). Kaplan–Meier estimate showed no significant difference in primary effectiveness outcome measure (freedom from all-cause death or non-fatal stroke) between both groups at follow-up (87.8% vs. 87.7%, p = NS). The incidence of transient ischemic attack or systemic embolism at follow-up was low (0% vs. 0.5% and 0.9% vs. 0%, respectively; each p = NS). Severe bleeding events after hospital discharge were rare (0% vs. 0.7%, p = NS). Conclusions: Patients with prior stroke demonstrated similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OAC for secondary stroke prevention in this selected group of nonvalvular AF patients. ClinicalTrials.gov identifier: NCT02230748. [ABSTRACT FROM AUTHOR]

BackgroundAtrial fibrillation (AF) poses significant thromboembolism and bleeding risks, especially in older adults. Warfarin continues to be a primary treatment option, and maintaining the Time in Therapeutic Range (TTR) is critical for ensuring its effectiveness. However, suboptimal TTR is associated with increased risks of stroke, bleeding, and mortality. Despite its importance, there is limited data on warfarin management in Ethiopian older adults with AF. Therefore, this study aimed to determine the TTR, bleeding events, and their determinants, in older patients with AF in Ethiopia receiving warfarin therapy.MethodIn this study, older patients with AF who were treated with warfarin and had follow-up visits between May 2021 and May 2024, and met the inclusion criteria, were included. Patients were categorized based on TTR into two groups: poor anticoagulation (TTR < 65%) and good anticoagulation quality (TTR ≥ 65%). Bivariate and Multivariate Logistic regression was performed to predict determinants of a TTR < 65% and bleeding events. Odds ratios with 95% confidence intervals (CIs) were calculated, and statistical significance was set at P < 0.05.ResultsIn this study, 384 patients with AF were included. Of this 53.4% were female. Of these 71% of patients had a TTR below 65%, 29% achieved ≥65%, with a median TTR of 45%. Bleeding events were reported by 13.5% of patients. Poor TTR was significantly associated with age (AOR = 1.199, 95% CI: 1.109–1.297), chronic kidney disease (AOR = 27.809, 95% CI: 7.57–101.76), and infrequent INR monitoring at 31–90-day intervals (AOR = 0.15, 95% CI: 0.004–0.051). Regarding determinants of bleeding events, Patients with diabetes mellitus had a 2.6-fold higher bleeding risk (AOR = 2.585, 95% CI: 1.069–6.250), and a CHA2DS2-VASc score ≥3 significantly increased bleeding risk compared to scores ≤2 (AOR = 7.562, 95% CI: 2.770–20.640).ConclusionThis study highlights suboptimal warfarin therapy among older Ethiopian patients with AF. Poor anticoagulation was associated with advanced age, chronic kidney disease, and infrequent INR monitoring, while diabetes mellitus and high CHA₂DS₂-VASc scores increased bleeding risks. Close monitoring and frequent INR checks are essential to improving outcomes.

Background Mitral valve transcatheter edge‐to‐edge repair (M‐TEER) has emerged as a viable therapy option in patients with severe mitral regurgitation and high surgical risk. Although atrial fibrillation is common among patients undergoing M‐TEER, the optimal anticoagulatory treatment after the intervention is unknown. Methods A single‐center retrospective observational analysis was conducted using data from the M‐TEER registry at the University Hospital Cologne collected from 2019 untill 2021 including patients undergoing M‐TEER between November 2012 and April 2019. Patients with atrial fibrillation receiving consistent anticoagulation following M‐TEER were categorized into a direct oral anticoagulant or a vitamin K antagonist (VKA) group. The primary end point was a composite of ischemic cerebrovascular and bleeding events. Additionally, overall survival was assessed. Results Among 613 patients undergoing M‐TEER, 206 met the inclusion criteria, with 61 receiving direct oral anticoagulants and 145 receiving VKAs. After a median follow‐up of 833 (interquartile range, 355–1271) days, the incidence of the composite primary end point did not differ between direct oral anticoagulant and VKA groups (hazard ratio [HR], 0.51 [95% CI, 0.23–1.12]; P=0.07). Similarly, rates of ischemic cerebrovascular events and bleeding events were similar between groups. However, the overall mortality rate was higher in the VKA group (HR, 2.56 [95% CI, 1.54–4.26]; P=0.002). In the multivariable analysis, oral anticoagulation with a VKA was an independent predictor for death (adjusted HR, 2.23 [95% CI, 1.08–5.06]; P=0.03). Conclusions Our findings suggest that direct oral anticoagulants may offer comparable efficacy and safety to VKAs in preventing thromboembolic events following M‐TEER in patients with atrial fibrillation. Further randomized trials are needed to confirm these results and establish optimal anticoagulation strategies in this patient population.

This study aimed to investigate the impact of the drug–drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05–7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21–10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028–8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Abstract Background Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. Methods Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. Results Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p

We conducted a systematic review aiming to summarize the data on the current hemorrhage prediction models and evaluate their potential for generalized application in the neonatal population. The electronic databases PubMed and Scopus were searched, up to September 20, 2023, for studies that focused on development and/or validation of a prediction model for bleeding risk in neonates, and described the process of model building. Nineteen studies fulfilled the inclusion criteria for the present review. Eighteen bleeding risk prediction models in the neonatal population were identified, four of which were internally validated, one temporally and one externally validated. The existing prediction models for neonatal hemorrhage are mostly based on clinical variables and do not take into account the clinical course and hemostatic profile of the neonates. Most studies aimed at predicting the risk of intraventricular hemorrhage (IVH) reflecting the fact that IVH is the most frequent and serious bleeding complication in preterm neonates. A justification for the study sample size for developing the prediction model was given only by one study. Prediction and stratification of risk of hemorrhage in neonates is yet to be optimized. To this end, qualitative standards for model development need to be further improved. The assessment of the risk of bleeding incorporating platelet count, coagulation parameters, and a set of relevant clinical variables is crucial. Large, rigorous, collaborative cohort studies are warranted to develop a robust prediction model to inform the need for transfusion, which is a fundamental step towards personalized transfusion therapy in neonates. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. Methods: Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. Results: Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes. Conclusions: Coagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports. Trial registration ACTRN12620000421932 (https://covid19.cochrane.org/studies/crs-13513201). Clinical Perspective: Coagulation disorders such as thrombotic or hemorrhagic events are frequent in COVID-19 ARDS patients receiving ECMO. While older age, pre-existing cardiac disease, and diabetes were independently associated with bleeding, prone positioning and a longer time from admission to ECMO were associated with a higher percentage of thrombotic events. A longer duration of ECMO was linked to an increased rate of combined hemorrhagic and thrombotic events. [ABSTRACT FROM AUTHOR]

Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; <20–30 × 109/L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient‐ and disease‐related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient‐centric approach. Currently, evidence‐based recommendations and validated tools are lacking to support decision‐making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk‐based and individualised management of bleeding and thrombosis risk in adults with primary ITP. [ABSTRACT FROM AUTHOR]

Background: “Atrial fibrillation (AF)” is a prevalent cardiac arrhythmia connected with augmented risk of stroke and bleeding events. Despite advancements in treatment strategies, managing AF remains challenging due to its multifactorial nature. Objective: This longitudinal research aimed to assess the risk factors and outcomes in subjects with AF over a specified period, focusing on stroke and bleeding events. Methods: Electronic health records of AF subjects were analyzed over a defined research period. Demographic information, comorbidities, medication history, and laboratory parameters were extracted. Stroke and bleeding events were identified, and statistical analyses were performed. Results: The research cohort comprised 800 AF subjects with a mean follow-up duration of 3 years. Significant risk factors for stroke and bleeding events included advancing age, hypertension, and anticoagulant use. The incidence of stroke and bleeding events augmented over the follow-up period, with notable differences in rates between patient subgroups. Conclusion: This longitudinal analysis provides valuable insights into the risk factors and outcomes connected with AF, particularly stroke and bleeding events. The findings underscore the importance of proactive management strategies and personalized care approaches to optimize patient outcomes in AF.

Abstract Background Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. Objective The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. Methods An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. Results We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874–7.036, P 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). Conclusion The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Abstracts: Background: Management with warfarin therapy becomes challenging globally due to the increased risk of adverse clinical outcomes from its use. In Africa, warfarin-related bleeding events and thromboembolic complications range from 0.006 % to 59 % and 1.6 %–7.5 %, respectively. Objectives: This study aimed to determine adverse clinical outcomes of warfarin therapy and predictors among adult outpatients at Wallaga University Referral and Nekemte Comprehensive Specialized Hospitals from April 1, 2021 to March 31, 2023. Methods: An institutional-based retrospective cross-sectional study was conducted from June 1 to July 31, 2023, by reviewing the patient's medical charts with warfarin indications. Descriptive statistics such as frequencies, percentages, means, and standard deviations were computed. Bivariable and multivariable logistic regression analyses were performed to check the association between dependent and independent variables. In multivariable logistic regression analysis, an adjusted odds ratio (AOR) with 95 % CI was determined and statistical significance was declared at a p-value

Background and aim: Rivaroxaban is an emerging oral anticoagulant for postoperative anticoagulation after percutaneous left atrial appendage closure (LAAC). Because a once-daily dosing regimen of rivaroxaban causes fluctuations in the drug plasma concentration, we studied the feasibility and safety of twicedaily rivaroxaban as a postoperative anticoagulation regimen for patients with atrial fibrillation (AF) undergoing LAAC. Methods: This study involved patients with AF who underwent LAAC and took rivaroxaban postoperatively. A total of 326 patients who received a standard total dose (15 or 20 mg) of rivaroxaban based on their creatinine clearance rate were divided into the twice-daily (BID) rivaroxaban group (n = 208) and once-daily (QD) rivaroxaban group (n = 118) according to their anticoagulation strategy. Transesophageal echocardiography was recommended at 3-6 months postoperatively to check for device-related thrombosis (DRT). Clinical outcomes were evaluated during postoperative anticoagulation. Results: The median CHA2DS2-VASc score (4 [3, 5] vs. 4 [3, 5], p = 0.28) and HASBLED score (2 [2, 3] vs. 2 [2, 3], p = 0.48) were not significantly different between the groups. During the anticoagulation period (4.1 ± 0.7 vs. 4.1 ± 0.9 months, p = 0.58), 148 (71.2%) patients in the BID group and 75 (63.6%) in the QD group underwent follow-up transesophageal echocardiography. There were no statistically significant differences between the two groups in terms of DRT (1.4% vs. 2.7%, p = 0.60), minor bleeding (8.2% vs. 11.0%, p = 0.39), thromboembolic events (1.0% vs. 0.8%, p = 1.00), major bleeding (0.5% vs. 0.8%, p = 1.00), or death. Conclusion: A short course of twice-daily rivaroxaban following LAAC is a feasible alternative regimen with a low rate of major bleeding events, DRT, and thromboembolic events for patients with AF. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. Objective: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. Methods: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. Results: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874–7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). Conclusion: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021). Key messages: What is already known on this topic: Indobufen is comparable to aspirin in the treatment of atherosclerotic ischemic heart and peripheral vascular diseases, but the effect on minor ischemic stroke or high-risk TIA secondary prevention is unclear. What this study adds: The Randomized Controlled Clinical Study of Clopidogrel with Indobufen or Aspirin in Minor Ischemic Stroke or High-risk Transient Ischemic Attack suggests that combination of indobufen and clopidogrel has demonstrated superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA. Our trial results suggest that initiating dual antiplatelet therapy within 72 h is still beneficial for the patients with minor stroke and high-risk TIA, suggesting the possibility of expanding the time window of dual antiplatelet therapy. How this study might affect research, practice or policy: The result of the trial may provide a better dual antiplatelet therapeutic regimen for minor ischemic stroke or high-risk TIA secondary prevention. [ABSTRACT FROM AUTHOR]

The objective of this study is to examine the effectiveness and safety of zanubrutinib, rituximab, and lenalidomide (ZR2) in unfit patients with diffuse large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR2 regimen, especially when antiplatelet agents were co-prescribed, was also evaluated. We retrospectively reviewed unfit newly diagnosed (ND) and refractory or relapsed (R/R) patients with DLBCL who were administered with ZR2 regimen in two medical centers between December 2019 and February 2022. Response rates, progression-free survival (PFS), overall survival (OS), bleeding adverse events (AEs), and thrombosis episodes were analyzed. Furthermore, we investigated the effects of zanubrutinib alone or in combination with lenalidomide on platelet functions in vitro and in vivo. A total of 30 unfit patients (13 ND DLBCL and 17 R/R DLBCL patients) who received ZR2 regimen were enrolled in the study (median age: 69.5 years). The ultimate ORRs for the ND DLBCL and R/R DLBCL were 77.0% and 50.1%, respectively. The median follow-up was 16.6 months. The median PFS and OS were not achieved during the follow-up time. Subcutaneous hemorrhage AEs occurred in four cases, three cases suffered severe bleeding events, and thrombosis events were observed in two patients. ZR2 regimen inhibited platelet functions (aggregation, clot retraction, spreading and activation) in vitro and in vivo function testing especially in response to collagen. ZR2 is an efficient treatment option for unfit patients with DLBCL and could be well tolerated. Notably, this regimen inhibited platelet functions. Antiplatelet agents should be used with caution in patients treated with this regimen. [ABSTRACT FROM AUTHOR]

During the past decade, direct oral anticoagulants (DOACs) have advanced and simplified the prevention and treatment of venous thromboembolism (VTE). However, there remains a high incidence of bleeds, which calls for agents that have a reduced risk of bleeding. Factor XI (FXI) deficiency is associated with lower rates of venous thrombosis and stroke compared to the general population with a lower risk of bleeding. In conjunction with this, phase 2 studies have demonstrated safety and the potential for reduced thrombotic events with FXI inhibitors as compared to currently available medications. The aim of this review is to summarize key data on the clinical pharmacology of FXI, the latest developments in clinical trials of FXI inhibitors, and to describe the efficacy and safety profiles of FXI inhibitors for the prevention of venous and arterial thromboembolism. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell-associated coagulopathy can cause bleeding events. To explore risk factors for hemorrhage after CAR T-cell therapy, we retrospectively analyzed routine indicators in 56 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia who received anti-CD19 CAR T-cell therapy. Disturbance of coagulation occurred mainly within one month post infusion, especially on day 7 and 14. The cumulative incidence of bleeding events within one month was 32.8%, with the median onset of 7 (range, 0–28) days. All bleeding events were grade 1–3. Patients who experienced bleeding events within one month had longer prothrombin time, higher IL-6, higher IL-10, and lower platelets before lymphodepletion. There were also correlations among coagulation-, inflammatory-, and tumor burden-related markers. Multi-variate analysis showed IL-10 (> 7.98 pg/mL; adjusted odds ratio [OR], 13.84; 95% confidence interval [CI], 2.03–94.36; P = 0.007) and the endothelial activation and stress index (EASIX, defined as dehydrogenase [U/L] × creatinine [mg/dL] / platelets [×109 cells/L]; >7.65; adjusted OR, 7.06; 95% CI, 1.03–48.23; P = 0.046) were significant risk factors for bleeding events. IL-10 plus the EASIX defined three risk groups for bleeding events with cumulative incidence of 100% (hazard ratio [HR], 14.47; 95% CI, 2.78–75.29; P < 0.0001), 38.5% (HR, 3.68; 95% CI, 0.82–16.67; P = 0.089), and 11.8% (reference), respectively. Future studies are needed to verify the risk assessment models for bleeding events after CAR T-cell treatment in larger cohorts. [ABSTRACT FROM AUTHOR]

Bivalirudin, as a direct thrombin inhibitor, is considered to be safer compared with other anticoagulants, such as heparin; however, relevant data in China are unclear. The present study aimed to compare the safety of bivalirudin and heparin as anticoagulants in Chinese patients who underwent percutaneous coronary intervention (PCI). In the present study, 2,377 patients with ST-segment elevation myocardial infarction (STEMI), unstable angina, non-STEMI or stable coronary artery disease who underwent primary PCI while receiving bivalirudin or heparin (low molecular weight heparin or unfractionated heparin) were reviewed, and then analyzed as the bivalirudin group (n=944) and heparin group (n=1,433). The net adverse clinical events (NACEs) within 30 days were obtained, which were defined as major adverse cardiac and cerebral events (MACCEs) + Bleeding Academic Research Consortium (BARC) grade 2-5 bleeding events. Compared with the heparin group, the incidence of NACEs was reduced in the bivalirudin group (9.3 vs. 13.4%; P=0.003). However, no discrepancy was found in the incidence of MACCEs between the groups (5.9 vs. 7.6%; P=0.116). Moreover, the incidences of BARC 2-5 (4.8 vs. 8.7%; P<0.001) and BARC 3-5 bleeding events (1.9 vs. 4.4%; P=0.001) were decreased in the bivalirudin group compared with the heparin group. Following adjustment using multivariate logistic regression analysis, bivalirudin treatment (vs. heparin treatment) was independently associated with lower risks of NACEs [odds ratio (OR), 0.587; P<0.001], MACCEs (OR, 0.689; P=0.041) and BARC 2-5 (OR, 0.459; P<0.001) and 3-5 bleeding events (OR, 0.386; P=0.002). Overall, the present study demonstrated that bivalirudin decreased the risks of NACEs and bleeding events compared with heparin in Chinese patients who undergo PCI. However, further validation is required. [ABSTRACT FROM AUTHOR]

Transthyretin amyloidosis (ATTR) is a group of diseases caused by the deposition of insoluble fibrils derived from misfolded transthyretin, which compromises the structure and function of various organs, including the heart. Thromboembolic events and increased bleeding risk are among the most important complications of ATTR, though the underlying mechanisms are not yet fully understood. Transthyretin plays a complex role in the coagulation cascade, contributing to the activation and regulation of the coagulation and fibrinolytic systems. The prevalence of atrial fibrillation, cardiac mechanical dysfunction, and atrial myopathy in patients with ATTR may contribute to thrombosis, though such events may also occur in patients with a normal sinus rhythm and rarely in properly anticoagulated patients. Haemorrhagic events are modest and mainly linked to perivascular amyloid deposits with consequent capillary fragility and coagulation anomalies, such as labile international-normalised ratio during anticoagulant therapy. Therefore, it is paramount to carefully stratify the thrombotic and haemorrhagic risks, especially when initiating anticoagulant therapy. Our review aims to ascertain the prevalence of thromboembolic and haemorrhagic events in ATTR and identify potential risk factors and predictors and their impact on antithrombotic therapy. [ABSTRACT FROM AUTHOR]

Abstract Aims Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co‐morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re‐hospitalizations. Methods and results We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow‐up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non‐bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71–82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow‐up of 651 (IQR 357–1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n = 21, 65.6%), and the other events were cerebral bleeding (n = 4, 12.5%), intraarticular bleeding (n = 2, 6.3%), urogenital bleeding (n = 2, 6.3%), haemorrhagic pericardial effusions (n = 1, 3.1%), subcutaneous hematomas (n = 1, 3.1%), and haemothorax (n = 1, 3.1%). There was a significantly lower haemoglobin level (P

The relationship between coronary artery calcium (CAC) and bleeding events after percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) is not well established. This study aimed to examine the association between CAC scores and clinical outcomes after PCI in patients with CCS. This retrospective observational study included 295 consecutive patients who underwent multidetector computer tomography and were scheduled for their first elective PCI. Patients were categorized into two groups based on the CAC scores (low: ≤ 400 or high: > 400). The bleeding risk was evaluated using the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The primary clinical outcome was a major bleeding event within 1 year after PCI, defined as Bleeding Academic Research Consortium (BARC) 3 or 5. The high CAC score group had a higher proportion of patients meeting the ARC-HBR criteria than the low CAC score group (52.7% vs. 31.3%, p < 0.001). Kaplan–Meier survival analysis showed that the incidence of major bleeding events was higher in the high CAC score group as compared to the low CAC score group (p < 0.001). Furthermore, multivariate Cox regression anal ysis revealed that a high CAC score was an independent determinant of major bleeding events during the first year after PCI. A high CAC score is significantly associated with the incidence of major bleeding events after PCI in CCS patients. [ABSTRACT FROM AUTHOR]

Abstract Background The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome. Methods We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS). Results During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p

Aims: Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co‐morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re‐hospitalizations. Methods and results: We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow‐up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non‐bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71–82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow‐up of 651 (IQR 357–1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n = 21, 65.6%), and the other events were cerebral bleeding (n = 4, 12.5%), intraarticular bleeding (n = 2, 6.3%), urogenital bleeding (n = 2, 6.3%), haemorrhagic pericardial effusions (n = 1, 3.1%), subcutaneous hematomas (n = 1, 3.1%), and haemothorax (n = 1, 3.1%). There was a significantly lower haemoglobin level (P < 0.01), higher proportion of inferior vena cava (IVC) diameter ≥21 mm (P < 0.01), and higher furosemide equivalent doses per kilogram (P < 0.01) in the bleeding group than non‐bleeding group. A multivariate analysis revealed an equivalent dose of furosemide per kilogram ≥0.66 mg/kg (hazard ratios (HR) of 2.64, 95% confidence interval (CI) 1.26–5.68, P = 0.01), haemoglobin ≤10.3 g/dL (HR of 2.43, 95% CI 1.14–5.03, P = 0.02), and IVC diameter ≥21 mm (HR of 2.79, 95% CI 1.16–6.29, P = 0.02) were independently associated with bleeding events. The Kaplan–Meier analysis showed that HF re‐hospitalization rates were higher in the bleeding group than non‐bleeding group (P = 0.04). Conclusions: High doses of oral loop diuretics, IVC dilatation, and anaemia were predictors of bleeding events in patients hospitalized with ADHF patients. In addition, bleeding events were associated with HF re‐hospitalizations. [ABSTRACT FROM AUTHOR]

Background Patients with atrial fibrillation (AF) are likely to have a poor prognosis including bleedings following transcatheter aortic valve replacement (TAVR). Closure time of adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test and is a predictor of bleeding events following TAVR. We aimed to evaluate the impact of ongoing primary hemostatic disorders on bleeding events in TAVR patients with AF. Methods We enrolled 878 patients from our prospective registry. The primary endpoint was VARC-2 major/life-threatening bleeding complications (MLBCs) at 1 year after TAVR and secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year, defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Ongoing primary hemostatic disorder was defined by a postprocedural CT-ADP >180 seconds. Results Patients with AF had a higher incidence of MLBCs (20 vs. 12%, p = 0.002), MACCE (29 vs. 20%, p = 0.002), and all-cause mortality (15 vs. 8%, p = 0.002) within 1 year compared to non-AF patients. When the cohort was split into four subgroups according to AF and CT-ADP >180 seconds, patients with AF and CT-ADP >180 seconds had the highest risk of MLBCs and MACCE. Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP >180 seconds had 3.9-fold higher risk of MLBCs, whereas those patients were no longer associated with MACCE after the adjustment. Conclusion In TAVR patients, AF with postprocedural CT-ADP >180 seconds was strongly associated with MLBCs following TAVR. Our study suggests that persistent primary hemostatic disorders contribute to a higher risk of bleeding events particularly in AF patients.

Direct oral anticoagulants (DOACs) are widely employed for antithrombotic prophylaxis in patients with atrial fibrillation (AF). However, there is still uncertainty about their risk-benefit profile in older patients. Here, we evaluated the efficacy, safety, and dose appropriateness of DOACs in a real-world population of outpatients with non-valvular AF, with a specific focus on subjects aged over 80 years and/or with reduced renal function. Single-center retrospective study including patients who had been prescribed a DOAC between May 2014 and May 2021 for long-term anticoagulation in non-valvular AF. Patients anticoagulated for <4 weeks were excluded. The primary efficacy outcome was a composite of cardiovascular (CV) death, stroke, or systemic embolism. The primary safety outcome was major bleeding. A total of 1154 patients (median age 84 yrs., range 57–100 yrs.), among which 862 were 80 years and older, were included. In the subgroup of subjects ≥80 yrs., a subtherapeutic dose of DOAC was associated with an increased incidence of CV mortality, stroke, or systemic embolism (multivariable Cox regression, HR = 2.09, 95 % CI: 1.09–4.02), with no benefit in terms of prevalence of bleeding events (21.5 % vs. 18.6 %, p = 0.428), and the incidence of adverse safety and efficacy outcomes was not increased in patients with a reduced renal function (eGFR ≤30 mL/min). Plasma concentration of DOACs, assessed in a subset of 367 patients, did not increase with advanced age (≥ 80 yrs., two-way ANOVA, p = 0.656) nor with declining eGFR (≤30 mL/min, two-way ANOVA, p = 0.643) and was not associated with adverse safety and efficacy outcomes. Data from our study support the use of DOACs in populations of older adults and remark on the risks associated with inappropriate prescriptions in terms of CV mortality and adverse events. [ABSTRACT FROM AUTHOR]

Background: Clinical trials used Cockcroft-Gault (CG) formula to calculate the estimated glomerular filtration rate (eGFR) in order to dose rivaroxaban for patients with atrial fibrillation (AF). Objectives: The aim of this study is to evaluate rivaroxaban dosing appropriateness in patients with AF with or without renal impairment based on the CG formula and other formulae, including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the isotope dilution mass spectrometry (IDMS) traceable Modification of Diet in Renal Disease (MDRD) Study equation and the associated clinical outcomes. Methodology: A retrospective cohort study conducted at Sultan Qaboos University Hospital (SQUH) from 1st January 2016 to 31st December 2020, included all adult patients (≥ 18 years) treated with rivaroxaban for AF and followed up for one year after starting the treatment. Results: Based on the CG formula, the rivaroxaban dose was inappropriately prescribed in 27% of the patients (21% overdosed and 6% underdosed). Higher baseline creatinine (P=0.0014) and concurrent use of antiplatelet therapy (P<0.001) were associated with the tendency to rivaroxaban overdosing. Higher Body Mass Index (BMI) (P=0.002), female sex (P=0.032), and CKD (P=0.003) were associated with rivaroxaban underdosing. The degree of agreement between the renal function tests when comparing MDRD vs CG and CKD-EPI vs CG in terms of estimated glomerular filtration rate/creatine clearance (eGFR/CrCl) calculation was moderate (κ=0.46) and poor (κ=0.00), respectively, while, in terms of rivaroxaban dose appropriateness was almost perfect (κ=0.82) and substantial (κ=0.77). Clinical outcomes measured by stroke and bleeding events were not significantly different according to the appropriateness of the rivaroxaban dose. Conclusion: This study has shown a relatively high consistency with the gold standard in dosing rivaroxaban in AF patients using CG formula. Treatment efficiency and safety were not affected by the proportion of dose inappropriateness found in this cohort. [ABSTRACT FROM AUTHOR]

Abstract Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). Methods The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. Findings The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Interpretation Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.

Background: The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome. Methods: We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS). Results: During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups. Conclusions: In ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS. [ABSTRACT FROM AUTHOR]

Aims: The risk of ticagrelor‐related bleeding events remains a major clinical concern, especially in East Asian populations. Previous studies have reported higher ticagrelor exposure in Asian patients than in Caucasians. This prompted us to investigate the correlation between ticagrelor concentrations and bleeding events. Methods: Patients diagnosed with acute coronary syndrome and receiving dual antiplatelet therapy (aspirin and ticagrelor) were enrolled and followed up for 12 months. Trough plasma concentrations of ticagrelor and a major active metabolite were assayed, and 10 single nucleotide polymorphisms associated with ticagrelor pharmacokinetics and safety were also identified. Results: A total of 631 patients were included and 133 patients had bleeding academic research consortium type 1 or 2 bleeding event. The median ticagrelor concentration (interquartile range) was significantly higher in patients with bleeding events than that in patients without bleeding events (322.6 ng/mL [196.2–458.0 ng/mL] vs. 222.1 ng/mL [140.4–341.9 ng/mL], P <.001). According to the receiver operating characteristic curve, the cut‐off value for ticagrelor levels predicting bleeding events was 363.3 ng/mL (area under the curve = 0.65; P <.001, 95% Cl: 0.595–0.700). Pharmacogenomics results showed that P2Y12 (rs6787801, P =.024) and P2Y12 (rs6785930, P =.048) were statistically associated with ticagrelor levels and bleeding events, respectively. Conclusion: Ticagrelor plasma concentrations were associated with bleeding events in Chinese patients with acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Background and purpose: To explore the relationship between baseline levels of matrix metalloproteinase 9 (MMP9) in peripheral blood and the outcomes in patients with acute minor stroke and transient ischemic attack (TIA). Methods: We assessed data from patients with acute minor ischemic stroke or TIA who were included in the CHANCE (Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events) trial. Baseline level of MMP9 in peripheral blood is classified into five quintiles. We assessed the relationship between the baseline MMP9 and outcomes of stroke recurrence, composite vascular events, and poor functional outcomes within 90 days after stroke onset. Results: Of the 3014 patients included, 295 (9.79%) had recurrent stroke, 289 (9.59%) had recurrent ischemic stroke, 297 (9.85%) had combined vascular events, and 199 (6.64%) had poor functional outcomes within 90 days. We used MMP9 concentrations near hazard ratio (HR) = 1 (Q3) in restricted cubic splines as the reference. The result showed that, compared to patients in the Q3 group, patients in the highest quintile (Q5 group) had an increased risk of poor functional outcomes at 90 days after adjusting the risk factors and confounders (p = 0.030), which may be associated with an increased risk of combined vascular events (p = 0.052). Using Cox regression models or logistic regression models with restricted cubic spline, we also observed that higher MMP9 ratios were associated with an increased risk of stroke recurrence, combined events, and poor functional outcomes at a range of concentrations. Conclusions: For patients with acute minor stroke or TIA, higher baseline MMP9 level was associated with an increased risk of poor functional outcomes, which might be related to stroke recurrence and combined vascular events. [ABSTRACT FROM AUTHOR]

The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention. We have reported a simplified HBR (S-HBR), excluding six items with prevalences under 1% from ARC-HBR. The Japanese Circulation Society developed an HBR specific to Japanese (J-HBR), adding three items to ARC-HBR in consideration of ethnicity. Data comparing each HBR are scarce. Patients treated with second-generation drug-eluting stents between January 2010 and December 2013 were enrolled, in whom all items of ARC-HBR, and the incidences of major bleeding and ischemic events were examined. Also, the diagnostic values of ARC-HBR, S-HBR, and J-HBR at 1 and 7 years post procedure were compared by using receiver-operating characteristic curves. The study sample consisted of 3430 patients. Mean follow-up period was 2299 ± 904 days. The incidence of major bleeding at 1 and 7 years in each definition was as follows: ARC-HBC, 3.3% and 10.6%; S-HBR, 3.3% and 10.7%; and J-HBR, 2.9% and 10.0%. The diagnostic value of J-HBR for major bleeding at 1 year was lower than that of ARC-HBR (C statistics 0.64 vs. 0.68, p < 0.001). Other diagnostic values of S-HBR and J-HBR were comparable to those of ARC-HBR. S-HBR was as useful as ARC-HBR in predicting both short- and long-term HBR, and J-HBR is useful for predicting long-term HBR. [Display omitted] • Simplified high bleeding risk (S-HBR) consists of 11 factors which had prevalence greater than 1%. • S-HBR had similar diagnostic value of bleeding and ischemic events with Academic Research Consortium for High Bleeding Risk (ARC-HBR). • Japan HBR was able to predict larger number of at-risk patients than ARC-HBR. [ABSTRACT FROM AUTHOR]

This article discusses the genetic factors that contribute to bleeding events induced by the anticoagulant drug rivaroxaban. Rivaroxaban is commonly used for stroke prevention in patients with atrial fibrillation, but it carries a risk of major bleeding events, particularly in elderly patients. The article highlights the importance of considering potential side effects and genetic variations when prescribing rivaroxaban. The study identifies 18 genetic variants from 14 genes that may serve as biomarkers for understanding the adverse effects of rivaroxaban. These findings have implications for the development of preventive strategies and may also apply to other anticoagulant drugs. [Extracted from the article]

Background: This study aimed to investigate the effect of ticagrelor combined with omeprazole on patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Methods: Eighty-six patients with AMI who underwent primary PCI in Xinxiang Central Hospital between July 2015 and December 2016 were included and divided randomly into the observation group and the control group by the draw, with 43 patients in each group. All patients were routinely treated with dual antiplatelet therapy with aspirin plus ticagrelor. Omeprazole was used in the observation group and placebo was used in the control group. Data of baseline patient characteristics, platelet response index (PRI), ADP-induced platelet aggregation (ADP-Ag), major adverse cardiac events (MACE), and incidence of bleeding events were recorded and compared between both groups. Results: PRI and ADP-Ag at 7 days, 1 month, and 6 months after operation in both groups were significantly lower than those in the same group before administration (p

Patients treated with ticagrelor and aspirin usually suffer from bleeding events, especially mild bleeding which is one of the main factors reducing patients’ adherence to ticagrelor. The objective of this study is to investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin (50 mg) than that recommended by guidelines (75–100 mg). In this study, we prospectively enrolled 1220 patients who take ticagrelor in the hospital. After excluding the patients who did not take ticagrelor after discharge or lost to follow-up, the remaining 1066 patients were divided into two aspirin dose groups: 75–100 mg (n = 744) and 50 mg (n = 322). The rates of major adverse cardiovascular events (MACEs), bleeding events and ticagrelor adherence were compared between the two groups. MACEs risk was not significantly different between the two groups (OR = 0.563, 95% CI: 0.244–1.300, P = .179). However, 50 mg aspirin was associated with a lower risk of any Bleeding Academic Research Consortium (BARC) bleeding events (OR = 0.605, 95% CI: 0.399–0.713, P = .001), also lower BARC bleeding events (OR = 0.639, 95% CI: 0.468–0.872, P = .005). Moreover, lower-dose aspirin was associated with a lower rate of ticagrelor withdrawal (OR = 0.459, 95% CI: 0.279–0.754, P = .002), mainly because of the decrease in ticagrelor withdrawal due to bleeding (OR = 0.378, 95% CI: 0.156–0.916, P = .031). After propensity score matching (PSM), a total of 317 patients in each group were matched. The MACEs composite was not significantly different between the two matched groups and 50 mg aspirin was associated with a lower risk of bleeding events and low ticagrelor withdrawal before and after multivariate adjustment. In conclusion, among patients who took ticagrelor (90 mg twice daily), 50 mg aspirin daily is associated with a lower rate of bleeding events and ticagrelor withdrawal but does not increase the MACE risk compared with 75–100 mg aspirin daily.

Abstract Background Although bleeding events are the major concern when using oral anticoagulants, intrathoracic hemorrhages due to warfarin are rare. Most cases in the literature have been related to trauma and have manifested as a hemothorax. Here we report a case of a nontraumatic hemorrhage within a pre-existing pulmonary cyst that presented as a lung mass during warfarin therapy. Case presentation A 75-year-old asymptomatic woman presented with a 10-cm-diameter mass on chest radiography that was not evident 6 months prior. She had been taking warfarin for paroxysmal atrial fibrillation and a transient ischemic attack. There was no history of chest trauma, warfarin overdosing, or any suspected interactions with other drugs such as nonsteroidal anti-inflammatory drugs or antibiotics. The prothrombin time/international normalized ratio(PT-INR) was prolonged at 4.73 and her hemoglobin level was 8.7 g/dl. Chest computed tomography(CT)revealed an air-fluid mass adjacent to the right upper and middle lobes with a pleural effusion. A CT scan obtained 15 years prior revealed a cyst at the corresponding site and the mass was diagnosed as a warfarin-related hemorrhage within the pre-existing pulmonary cyst. We performed a surgical resection of the cyst to prevent any worsening hemorrhage and subsequent infection. The postoperative course was uneventful and the patient was discharged on the 3rd postoperative day. Conclusion A warfarin-related thoracic hemorrhage, other than a hemothorax, could manifest as a pulmonary mass on radiography in patients with pre-existing pulmonary cysts. History taking especially of any anticoagulant medications and a precise assessment of the past images are crucial for a correct diagnosis. Once the intrapulmonary cystic hemorrhage becomes evident, prompt withdrawal with a reversal of warfarin and surgical resection are required to prevent a worsening hemorrhage and subsequent infection.

Background: Blood coagulation dysfunction is a risk factor for adverse outcomes in patients with coronavirus disease 2019 (COVID-19), especially in severe cases. The evidence for the effects of anticoagulation therapy on prognosis of COVID-19 patients and its risk of causing bleeding events is accumulating. Here we conducted a meta-analysis to assess the efficacy and safety of anticoagulants in COVID-19 patients of different severity., Methods: We searched PubMed, Embase databases, Cochrane Trials, OVID MEDLINE from December 2019 to April 2023. We included randomized controlled trials (RCTs) involving COVID-19 patients over 18 years of age, which explored the effect of anticoagulant and its dose on outcomes including all-cause mortality, bleeding events or thrombotic events. We calculated the risk ratio (RR) and its 95% confidence interval (CI) for each outcome. We also performed subgroup analyses to assess the impact of disease severity, using a fixed-effect model to test for heterogeneity. The risk of bias, publication bias, and the quality of evidence were also evaluated., Results: A total of 20 RCTs were included for final analysis. When compared with standard care, anticoagulation treatment reduced all-cause mortality (RR 0.47, 95% CI: 0.29-0.76) and thrombotic events (RR 0.35, 95% CI: 0.15-0.83) in the whole population with COVID-19 (n=2,365), without increase in bleeding events (total: RR 1.47, 95% CI: 0.54-4.00). Most of the studies only enrolled non-severe patients (n=2,329), while the number of severe patients (n=36) was scarce. In RCTs compared therapeutical and prophylactic doses of anticoagulants, no significant difference in on all-cause mortality was found in the whole population and non-severe and severe subgroups (total: RR 1.01, 95% CI: 0.92-1.10; non-severe: RR 1.03, 95% CI: 0.81-1.32; severe: RR 1.00, 95% CI: 0.91-1.11). Therapeutical dose reduced risk of thrombotic events (total: RR 0.59, 95% CI: 0.48-0.73; subtotal of non-severe: RR 0.57, 95% CI: 0.39-0.84; Subtotal of severe: RR 0.61, 95% CI: 0.47-0.78), while risk of bleeding was increased (total: RR 1.98, 95% CI: 1.47-2.66; non-severe: RR 2.38, 95% CI: 1.56-3.62; severe: RR 1.63, 95% CI: 1.07-2.47). Study heterogeneity was found only in the analysis of effects of anticoagulants on risk of thrombotic events., Conclusions: Anticoagulant therapy reduces all-cause mortality and risk of thrombosis in non-severe COVID-19 patients. Therapeutic dose of anticoagulant therapy can be considered in both non-severe and severe COVID-19 patients to reduce thrombosis, but may be associated with increased bleeding events., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-744/coif). Y.W. receives National Natural Science Foundation of China (82200090). Y.S. receives funding from Shanghai Municipal Science and Technology Major Project (ZD2021CY001), National Natural Science Foundation of China (82130001, 82272243), Science and Technology Commission of Shanghai Municipality (20Z11901000, 20DZ2261200, 20XD1401200, 22Y11900800), Clinical Research Plan of SHDC (SHDC2020CR5010-002), Shanghai Municipal Key Clinical Specialty (shslczdzk02201) and Shanghai Municipal Health Commission and Shanghai Municipal Administrator of Traditional Chinese Medicine [ZY(2021-2023)-0207-01]. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). Methods: The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. Findings: The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Interpretation: Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning.Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC.Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 μg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC.Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.

Background: Antibiotic combination is commonly used to treat multidrug-resistant pathogens. Reports have indicated that tigecycline use is associated with hypofibrinogenemia. However, whether the bleeding risk of tigecycline is higher than that of other antibiotics remains unknown. The aim of this study was to compare the bleeding risk between colistin–tigecycline and colistin–carbapenem treatment. Methods: This retrospective cohort study enrolled adult patients treated with colistin along with tigecycline or carbapenems (doripenem, imipenem–cilastatin, or meropenem) for ˃72 hours during hospitalization. The primary outcome was major bleeding events, which were determined by a hemoglobin drop of ≥ 2 g/d and receipt of blood transfusions with whole blood or packed red blood cells. Multivariate logistic regression was applied to determine risk factors for bleeding events. Results: In total, 106 and 268 patients in the colistin–tigecycline and colistin–carbapenem groups met the criteria for analysis, respectively. The two groups did not differ significantly in demographic data, except for alanine aminotransferase (ALT), serum creatinine (SCr) and ulcer disease. The colistin–tigecycline group had a higher ALT, SCr and a lower proportion of ulcer disease. Major bleeding events did not differ significantly between the colistin–tigecycline and colistin–carbapenem groups (12.26% vs 9.33%, P = 0.40). Antibiotic duration [OR = 1.06 (1.02– 1.11), P=0.007)] and anticoagulant use [OR = 2.16 (1.05– 4.42), P=0.04] were associated with major bleeding events. Conclusion: Colistin–tigecycline treatment was not associated with a higher bleeding risk. Antibiotic duration and concurrent use of anticoagulant were the risk factors of bleeding events. [ABSTRACT FROM AUTHOR]

This study applied the Academic Research Consortium for HBR (ARC-HBR) criteria to peripheral artery disease (PAD) patients after Endovascular therapy (EVT) and assessed the prevalence of HBR, as well as the association between HBR and clinical outcomes. This is a single-center, non-randomized, controlled, and retrospective study. EVTs for symptomatic PAD are minimally invasive and efficient. Although bleeding can be a serious adverse event, the criteria for HBR and assessment of bleeding events in patients who underwent EVT have been limited. A total of 156 patients with PAD who underwent EVT were divided into two groups according to ARC-HBR criteria. The associations between HBR and bleeding events, which was defined as Bleeding Academic Research Consortium Type 3 or Type 5 bleeding within 1 year and all-cause mortality within 1 year, were analyzed. The percentage of patients who were categorized as having HBR was 75.0%. Bleeding events occurred in 12.6% of the patients. All bleeding events occurred in the HBR group, while no bleeding events occurred in the no-HBR group. (16.9% vs. 0.0%, respectively; p = 0.008). During the follow-up period, 11.1% of the patients had died. All-cause mortality was significantly higher in the HBR group than in the no-HBR group (14.7% vs. 0.0%, respectively; p = 0.019). Most patients with PAD were classified as having HBR as assessed by ARC-HBR criteria, and patients with HBR were at a higher risk of not only bleeding events but also mid-term mortality compared to those without HBR. ARC-HBR criteria can be a helpful parameter when treating PAD patients after EVT. [ABSTRACT FROM AUTHOR]