Hemorrhagic Events Research Articles

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies

PurposeIntracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal.MethodsA retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed.ResultsA total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001).ConclusionThis study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

Risk of death, thrombotic and hemorrhagic events in patients with atrial fibrillation and systemic autoimmune diseases

Abstract Background Growing evidence showing that systemic autoimmune diseases (SAD) are associated with a high risk of incident atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. Purpose To assess the risk of all-cause death, thrombotic events, and bleeding in AF patients with SAD. Methods Retrospective cohort study within a global health care network (TriNetx). Using ICD codes, AF patients were categorized into two groups: 1) AF patients with SAD (M32: Systemic Lupus Erythematosus; M33: Dermato-polymyositis; M34: Systemic Sclerosis; M35: Sjogren syndrome), and 2) AF controls (without systemic autoimmune, autoinflammatory, or rheumatic diseases). The primary outcomes were the 5-year risks of 1) all-cause death, 2) thrombotic events (ischemic stroke, transient ischemic attack, peripheral arterial thromboembolism, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and 3) hemorrhagic outcome (intracranial hemorrhage and gastrointestinal bleeding). Secondary outcomes were each component of the composite primary outcomes. Cox regression analysis before and after propensity-score-matching (PSM) was used to estimate HR and 95% confidence interval (95%CI). Sensitivity analyses were done to investigate the risk of primary outcomes associated with each systemic autoimmune disease and with different types of oral anticoagulant (OAC). Results We identified 22,371 AF patients with SAD (67.7±13.7 years, 72.2% females), and 1,478,693 AF controls (69.7±14.0, 42.6% females). Before PSM, AF patients with SAD were younger, more often females, and with a higher prevalence of cardiovascular risk factors; no differences were found after PSM. After PSM, AF patients with SAD showed a higher risk of all-cause death (HR 1.21, 95% 1.17-1.25), thrombotic events (HR 1.55, 95%CI 1.49-1.61), and hemorrhagic events (HR 1.39, 95%CI 1.32-1.46) compared to AF controls (Table 1). On sensitivity analyses, we found that the risk of primary outcomes in AF patients with SAD was independent from the OAC type, but NOAC was more effective than warfarin in reducing the risk of thrombotic events. The highest risk of all-cause death was associated with Systemic Sclerosis, while the highest risk of composite thrombotic events was associated with Systemic Lupus Erythematosus, and Dermato-polymyositis. The highest risk of stroke was associated with Sjogren syndrome; and myocardial infarction and deep vein thrombosis with Dermato-polymyositis, Systemic Lupus Erythematosus was associated with the highest risk of Intracranial hemorrhage, while Systemic Sclerosis to the highest risk of gastrointestinal bleeding (Table 2). Conclusion In AF patients the coexistence of SAD is associated with a high risk of all-cause death, thrombotic events, and bleeding. A personalized approach aimed to minimize the impact of SAD on the clinical course of AF patients is needed.Figure 1Figure 2

Non-alcoholic fatty liver disease in patients with atrial fibrillation: a report from a global federated health network

Abstract Background Few data are available on the clinical course of patients with Atrial Fibrillation (AF) and Nonalcoholic Fatty Liver Disease (NAFLD). Purpose To evaluate the 1-year risk of all-cause death, thromboembolic events, and bleeding in AF patients with NAFLD. Methods Retrospective cohort study within the global TriNetX platform. Patients with AF were categorized into two groups: i) AF with NAFLD and ii) AF without liver diseases. The primary outcomes were the 1-year risks of a composite outcome of i) all-cause death and thrombotic events (all-cause death, acute myocardial infarction, ischemic stroke, systemic arterial thromboembolism, deep vein thrombosis, and pulmonary embolism), and hemorrhagic outcome (intracranial hemorrhage and gastrointestinal bleeding). Secondary outcomes were each component of the composite primary outcomes. Cox regression analysis before and after propensity-score-matching (PSM) was used to estimate HR and 95% confidence interval (95%CI). Sensitivity analyses were done to investigate the risk associated with cirrhosis and type of oral anticoagulant. Results We identified 22,636 AF patients with NAFLD (69±12 years, 46.7% females) and 391,014 AF patients without NAFLD (72±12 years, 42.7% females). Before PSM, AF patients with NAFLD were younger, and with a higher prevalence of cardiovascular risk factors than those without liver disease. After PSM, no difference was found between the two groups, but NAFLD patients showed a higher 1-year risk of thrombotic (HR 1.54, 95%CI 1.47-1.61) and hemorrhagic (HR 1.56, 95%CI 1.42-1.72) composite outcomes (Figure 1). The higher risk in NAFLD was consistent also for all the secondary outcomes (Figure 1). On the sensitivity analyses (Figure 2), a progressively increased risk of thrombotic and hemorrhagic events was found in non-cirrhotic and cirrhotic patients compared to patients without liver diseases, whereas non-vitamin-k antagonist (NOAC) seems to be safer and more effective than warfarin. Conclusion In AF patients, NAFLD is associated with a higher 1-year risk of all-cause death, thrombotic and hemorrhagic events. Further studies are needed to establish the best clinical approach to manage NAFLD in AF patients.Figure 1Figure 2

Human atherosclerotic plaque transcriptomics reveals endothelial beta-2 spectrin as a potential regulator a leaky plaque microvasculature phenotype

The presence of atherosclerotic plaque vessels is a critical factor in plaque destabilization. This may be attributable to the leaky phenotype of these microvessels, although direct proof for this notion is lacking. In this study, we investigated molecular and cellular patterns of stable and hemorrhaged human plaque to identify novel drivers of intraplaque vessel dysfunction. From transcriptome data of a human atherosclerotic lesion cohort, we reconstructed a co-expression network, identifying a gene module strongly and selectively correlated with both plaque microvascular density and inflammation. Spectrin Beta Non-Erythrocytic 1 (sptbn1) was identified as one of the central hubs of this module (along with zeb1 and dock1) and was selected for further study based on its predominant endothelial expression. Silencing of sptbn1 enhanced leukocyte transmigration and vascular permeability in vitro, characterized by an increased number of focal adhesions and reduced junctional VE-cadherin. In vivo, sptbn1 knockdown in zebrafish impaired the development of the caudal vein plexus. Mechanistically, increased substrate stiffness was associated with sptbn1 downregulation in endothelial cells in vitro and in human vessels. Plaque SPTBN1 mRNA and protein expression were found to correlate with an enhanced presence of intraplaque hemorrhage and future cardiovascular disease (CVD) events during follow-up. In conclusion, we identify SPTBN1 as a central hub gene in a gene program correlating with plaque vascularisation. SPTBN1 was regulated by substrate stiffness in vitro while silencing blocked vascular development in vivo, and compromised barrier function in vitro. Together, SPTBN1 is identified as a new potential regulator of the leaky phenotype of atherosclerotic plaque microvessels.

#2147 Enoxaparin dosing in advanced chronic kidney disease: importance of monitoring with anti-Xa levels

Abstract Background and Aims Enoxaparin is a low-molecular-weight heparin (LMWH) that is commonly used in the prevention of deep venous thrombosis (DVT) and the treatment of acute thomboembolic diseases. Current literature indicates that in advanced chronic kidney disease (CKD), there is a reduced clearance and increased half-life of LMWH and therefore, a dose adjustment is recommended. The prescription label recommends a dose adjustment of enoxaparin to 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation when eGFR <30 ml/min. The aim of this study was to examine the accuracy of this dosing strategy to achieve the desired target of anticoagulation in advanced CKD. Method We conducted a prospective study in patients admitted from May 2019 to April 2023 in the Nephrology ward at our centre, who started anticoagulant treatment with enoxaparin during their in-hospital stay for prophylactic or therapeutic indications. We excluded patients with eGFR >30 ml/min at the onset of anticoagulation with enoxaparin. The dosing strategy was 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation in all patients. Blood samples were drawn 4 hours after the third dose of enoxaparin to monitor anti-Xa levels in all cases. Results The study included 153 patients; 70 patients with stage 4-5 CKD and 83 patients on renal replacement therapy. 132 patients (86.3%) received enoxaparin for a therapeutic indication, while 21 patients (13.7%) received it as prophylaxis of DVT. In patients receiving enoxaparin for a therapeutic indication, 73 patients (55.3%) reached the therapeutic target anti-Xa levels (0.6-1), while 32.6% of patients had peak anti-Xa levels below the therapeutic target (<0.6) and 12.1% were over-anticoagulated (>1). There was an inverse relationship between the proportion of patients who were adequately anticoagulated and CKD stage; 66.7%, 58.6% and 48.6% of patients reached the target peak anti-Xa levels in CKD stage 4, 5 and 5D respectively. There was no significant association between anti-Xa levels and obesity or liver disease. In patients receiving enoxaparin for prophylaxis of DVT, 42.9% reached the target anti-Xa levels for prophylaxis (0.3-0.6), while 38.1% had anti-Xa levels below this range and 19% were over-anticoagulated. Conclusion The enoxaparin dosing recommendations indicated by its label entails a high proportion of patients with advanced CKD who do not achieve the target therapeutic levels of antiXa, especially in patients on renal replacement therapy. To ensure adequate anticoagulation in these patients, we recommend using individualized dosing adjustments based on monitoring of anti-Xa levels for the prevention of thromboembolic events and reducing the risk of hemorrhagic events.

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside.

Acquired hemophilia A (AHA) is a bleeding disorder characterized by the immunological inhibition of factor VIII (FVIII) of the hemostatic pathway leading to hemorrhagic events. Different domains of FVIII are the target of autoantibodies (mainly immunoglobulin (Ig) G) leading to the deficiency of FVIII. Several factors have been associated with the activation of the auto-immunity towards FVIII. Emerging evidence implicates CD4+ T cell activation in mediating this autoimmune response, with their involvement like that observed in congenital hemophilia A. Several genes such as HLA II DRB*16, DQB1*0502, and CTLA-4 + 49 are responsible for the pathogenesis of AHA. Epigenetic modifications and mainly long-coding RNAS (lncRNAs) are potentially contributing to the pathogenesis of AHA. The treatment approach of AHA includes the management of acute bleeding events and the administration of immunosuppressive medications. This review aimed to summarize the published data on the genetics and epigenetics of AHA. The severity and the mortality of this disease are creating an emerging need for further research in the field of the genetics and epigenetics of acquired hemorrhagic disorder.

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.

Hemorrhage Sites and Mitigation Strategies After Pancreaticoduodenectomy

Postpancreatectomy hemorrhage is an uncommon but highly morbid complication of pancreaticoduodenectomy. Clinical evidence often draws suspicion to the gastroduodenal artery stump, even without a clear source. To determine the frequency of gastroduodenal artery bleeding compared to other sites and the results of mitigation strategies. This cohort study involved a retrospective analysis of data for consecutive patients who had pancreaticoduodenectomy from 2011 to 2021 at Memorial Sloan Kettering Cancer Center (MSK) and Thomas Jefferson University Hospital (TJUH). Demographic, perioperative, and disease-related variables. The incidence, location, treatment, and outcomes of primary (initial) and secondary (recurrent) hemorrhage requiring invasive intervention were analyzed. Imaging studies were re-reviewed by interventional radiologists to confirm sites. Inclusion criteria were met by 3040 patients (n = 1761 MSK, n = 1279 TJUH). Patients from both institutions were similar in age (median [IQR] age at MSK, 67 [59-74] years, and at TJUH, 68 [60-75] years) and sex (at MSK, 814 female [46.5%] and 947 male [53.8%], and at TJUH, 623 [48.7%] and 623 male [51.3%]). Primary hemorrhage occurred in 90 patients (3.0%), of which the gastroduodenal artery was the source in 15 (16.7%), unidentified sites in 24 (26.7%), and non-gastroduodenal artery sites in 51 (56.7%). Secondary hemorrhage occurred in 23 patients; in 4 (17.4%), the gastroduodenal artery was the source. Of all hemorrhage events (n = 117), the gastroduodenal artery was the source in 19 (16.2%, 0.63% incidence in all pancreaticoduodenectomies). Gastroduodenal artery hemorrhage was more often associated with soft gland texture (14 [93.3%] vs 41 [62.1%]; P = .02) and later presentation (median [IQR], 21 [15-26] vs 10 days [5-18]; P = .002). Twenty-three patients underwent empirical gastroduodenal artery embolization or stent placement, 7 (30.4%) of whom subsequently experienced secondary hemorrhage. Twenty percent of all gastroduodenal artery embolizations/stents (8/40 patients), including 13% (3/13 patients) of empirical treatments, were associated with significant morbidity (7 hepatic infarction, 4 biliary stricture), with a 90-day mortality rate of 38.5% (n = 5) for patients with these complications vs 7.8% without (n = 6; P = .008). Ninety-day mortality was 12.2% (n = 11) for patients with hemorrhage (3 patients [20%] with primary gastroduodenal vs 8 [10.7%] for all others; P = .38) compared with 2% (n = 59) for patients without hemorrhage. In this study, postpancreatectomy hemorrhage was uncommon and the spectrum was broad, with the gastroduodenal artery responsible for a minority of bleeding events. Empirical gastroduodenal artery embolization/stent without obvious sequelae of recent hemorrhage was associated with significant morbidity and rebleeding and should not be routine practice. Successful treatment of postpancreatectomy hemorrhage requires careful assessment of all potential sources, even after gastroduodenal artery mitigation.

Bleeding Outcomes of Direct Oral Anticoagulants and Vitamin K Antagonists for Acute Venous Thromboembolism: A Cross-Sectional Study.

Venous thromboembolism (VTE) is a widespread and significant cause of morbidity and mortality on a global scale. The primary objective of this cross-sectional study is to examine the impact of anticoagulant therapy on major organ hemorrhage events in patients diagnosed with acute venous thromboembolism (VTE). Specifically, this research compares the effects of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). This retrospective observational study examined the medical records of 46 patients who had been diagnosed with VTE and were receiving treatment with DOACs or VKAs. The documentation of patient characteristics encompassed demographic information, comorbidities, and treatment particulars. Within 30 days of hospital admission, the incidence of significant organ bleeding events, with an emphasis on gastrointestinal and intracranial hemorrhage, was the primary outcome evaluated. Overall, 46 patients with VTE who were treated with oral anticoagulation therapy participated in the study. Twenty-four and 22 patients were administered VKAs and DOACs, respectively. The similarity in baseline characteristics between the DOAC and VKA groups ensured that the analyses were well-matched. The examination of bleeding sites unveiled subtle variations, as the DOAC group exhibited a progressive increase in the incidence of intracranial bleeding (12, 55.5%), while the VKA group demonstrated a surge in upper gastrointestinal bleeding (12, 50%) as well. While lacking statistical significance, these observed patterns are consistent with prior research that indicates that DOACs may have a lower risk of catastrophic hemorrhage in comparison to VKAs. The overall in-hospital mortality rate for patients treated with VKA was 33.3% (n=8), while that treated with DOAC was 18.2% (n=4). These differences did not reach statistical significance (P>0.05). In a similar vein, the evaluation of mortality associated with hemorrhage revealed six (25%) in the group receiving VKA and three (13.6%) in the group receiving DOAC; the P value was not statistically significant (P>0.05). This study contributes valuable insights into bleeding outcomes associated with anticoagulant therapy for acute VTE. The nuanced differences in bleeding patterns highlight the complexity of anticoagulant selection, emphasizing the importance of considering bleeding site considerations. The comparable mortality rates support existing evidence regarding the favorable safety profile of DOACs.

Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19.

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20-0.45] events/day vs. 0.05% [95% CI 0.02-0.16]), with a 71% risk reduction (95% CI 22%-94%). The incidence of bleeding was 0.33% (95% CI 0.22-0.50) vs 0.14% events/day (95% CI 0.07-0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16-1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07-0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

Platelet and INR Thresholds and Bleeding Risk in Ultrasound Guided Percutaneous Liver Biopsy: A Before-After Implementation of the 2019 Society of Interventional Radiology Guidelines Observational Quality Improvement Study.

Purpose: To evaluate if implementation of the 2019 Society of Interventional Radiology (SIR) guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy is associated with increased haemorrhagic adverse events, change in pre-procedural blood product utilization, and evaluation of guideline compliance rate at a single academic institution. Methods: Ultrasound guided percutaneous liver biopsies from (January 2019-January 2023) were retrospectively reviewed (n = 504), comparing biopsies performed using the 2012 SIR pre-procedural coagulation guidelines (n = 266) to those after implementation of the 2019 SIR pre-procedural guidelines (n = 238). Demographic, preprocedural transfusion, laboratory, and clinical data were reviewed. Chart review was conducted to evaluate the incidence of major bleeding adverse events defined as those resulting in transfusion, embolization, surgery, or death. Results: Implementation of the 2019 SIR periprocedural guidelines resulted in reduced guideline non-compliance related to the administration of blood products, from 5.3% to 1.7% (P = .01). The rate of pre-procedural transfusion remained the same pre and post guidelines at 0.8%. There was no statistically significant change in the incidence of bleeding adverse events, 0.8% pre guidelines versus 0.4% post (P = 1.0). Conclusion: Implementation of the 2019 SIR guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy did not result in an increase in bleeding adverse events or pre-procedural transfusion rates. The guidelines can be safely implemented in clinical practice with no increase in major adverse events.

ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d'Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.

Research on electrical capacitance tomography (ECT) detection of cerebral hemorrhage based on symmetrical cancellation method

Currently, there is an urgent need for a fast and portable intracerebral hemorrhage (ICH) detection technology for pre-hospital emergency scenarios. Owing to the disproportionately elevated permittivity of blood compared to other brain tissues, Electrical Capacitance Tomography (ECT) offers a viable modality for mapping the spatial distribution of permittivity within the brain, thus facilitating the imaging-based identification of ICH. Currently, ECT is confined to time-differential imaging due to limited sensitivity, and this methodology requires non-hemorrhagic measurements for comparison, data that are frequently inaccessible in clinical contexts. To overcome this limitation, in accordance with the natural bilateral symmetry of the cerebral hemispheres, a symmetrical cancellation scheme is introduced. In this method, electrodes are uniformly arrayed around the cranial periphery and strategically positioned in a symmetrical manner relative to the sagittal suture. Subsequently, the measured capacitances for each electrode pair are subtracted from those of their symmetrical counterparts aligned with the sagittal suture. As a result, this process isolates the capacitance attributable solely to hemorrhagic events within a given hemisphere, permitting the absolute imaging of ICH. To assess the feasibility of this method, simulation and empirical imaging were conducted respectively on a numerical hemorrhage model and three physical models (a water-wrapped hemorrhage model, an isolated porcine fat-wrapped hemorrhage model, and an isolated porcine brain tissue-wrapped hemorrhage model). Traditional absolute imaging, time-differential imaging and symmetrical cancellation imaging were performed on all models. The results substantiate that the proposed imaging modality is capable of obtaining absolute imaging of ICH. But a mirrored artifact, symmetrical to the site of the actual hemorrhage image appeared in each of the imaging results. This mirror artifact was characterized by identical dimensions and an inverted pixel-value schema, an intrinsic consequence of the symmetrical cancellation imaging algorithm. The real image of hemorrhage can be ascertained through pre-judgment with the symptoms of the patient. Additionally, the quality of this imaging is seriously dependent on the precise alignment between the electrodes and the sagittal suture of the brain; even a minor deviation in symmetry could introduce excessive noises. Thus, the complicated operational procedures remain as challenges for practical application.

Safety and efficacy of stent-assisted coil embolization with periprocedural dual antiplatelet therapy for the treatment of acutely ruptured intracranial aneurysms.

Despite growing evidence for the effectiveness of stent-assisted coil embolization (SAC) in treating acutely ruptured aneurysms, the safety of stent placement in acute phase remains controversial because of concerns for stent-induced thromboembolism and hemorrhagic events attributable to the necessity of antiplatelet therapy. Therefore, we investigated the safety and efficacy of SAC with periprocedural dual antiplatelet therapy (DAPT) compared with the coiling-only technique to determine whether it is a promising treatment strategy for ruptured aneurysms. We retrospectively evaluated 203 enrolled patients with acutely ruptured aneurysms, categorizing them into two groups: SAC and coiling-only groups. Comparative analyses between the two groups regarding angiographic results, clinical outcomes, and procedure-related complications were performed. A subgroup analysis of procedural complications was conducted on patients who did not receive chronic antithrombotic medications to alleviate their influence before hospitalization. 130 (64.0%) patients were treated using the coiling-only technique, whereas 73 (36.0%) underwent SAC. There was a trend to a higher complete obliteration rate (p = 0.061) and significantly lower recanalization rate (p = 0.030) at angiographic follow-up in the SAC group compared to the coiling-only group. Postprocedural cerebral infarction occurred less frequently in the SAC group (8.2%) than in the coiling-only group (17.7%), showing a significant difference (p = 0.044). Although the ventriculostomy-related hemorrhage rate was significantly higher in the SAC group than in the coiling-only group (26.2% vs. 9.3%, p = 0.031), the incidence of symptomatic ventriculostomy-related hemorrhage was comparable. Subgroup analysis excluding patients receiving chronic antithrombotic medications showed similar results. SACwith periprocedural DAPT could be a safe and effective treatment strategy for acutely ruptured aneurysms. Moreover, it might have a protective effect on postprocedural cerebral infarction without increasing the risk of symptomatic hemorrhagic complications.

Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis.

There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.

Sacrococcygeal chordoma with spontaneous regression due to a large hemorrhagic component.

Chordoma is a malignant bone tumor originating from notochordal remnants, most commonly occurring at the sacrococcygeal junction. We present a case of a 70-year-old male with chronic pain in the lower lumbar spine. MRI performed elsewhere revealed a large tumor that involved S4, S5, and the coccyx with a presacral soft tissue component. The lesion was heterogeneously hyperintense on T2-weighted images with a thick hypointense rim anteriorly. On T1-weighted images, the lesion showed a native hyperintense signal centrally probably due to hemorrhage. Based on this MRI, the diagnosis of chordoma was suggested. A spontaneous marked reduction in size was observed on a 4-week interval MRI performed at our institution before biopsy. Due to spontaneous tumor shrinkage along with peripheral enhancement, a differential diagnosis of infection or bleeding in a retrorectal cyst was proposed. This case teaches us that chordomas may contain a large hemorrhagic component, which is hyperintense on T1-weighted images and shows peripheral rim enhancement. Spontaneous shrinkage of a tumor may occur due to the resolution of a hematoma within weeks. Biopsy is key to obtain the correct diagnosis. Understanding the typical and more rare features of chordomas is key for MSK radiologists as well as pathologists. Chordomas are typically slow-growing tumors, but radiologists should be aware that intratumoral hemorrhage can lead to rapid changes in tumor size, which may be mistaken for either regression or progression of tumor. This case highlights the importance of considering hemorrhagic events within chordomas in the differential diagnosis when observing size fluctuations on imaging.

Bleeding risk stratification in patients admitted for acute coronary syndrome

Abstract Funding Acknowledgements None. Introduction The risk of hemorrhagic events should always be accounted for in patients admitted with acute coronary syndromes (ACS). With the increasing frailty of these patients, it is important to identify them and minimize the risk of such events. Purpose Identify high-risk patients admitted for ACS for hemorrhagic events during their hospital stay. Methods Multicenter retrospective study, data collected from 1/10/2010 and 31/12/2020 with ACS diagnosis. Patients were divided into 3 groups according to hemoglobin (Hb) and platelet (Plat) levels. Group 1 – Hb &amp;lt;8g/dl, Plat &amp;lt;150x109/L; Group 2 – Hb 8-12g/dl, Plat 150-450x109/L; Group 3 – Hb ≥12g/dl, Plat ≥450x109/L. We further divided these patients according to a composite endpoint. Group A without the composite endpoint; Group B with composite endpoint. This composite endpoint was defined as major hemorrhage, intracranial hemorrhage, need of blood transfusions and a Hb decrease of ≥ 2g/dl. Results 19409 patients were enrolled, of those 4707 (24.3%) had the composite endpoint. Group B was older (68±13 vs 66±12, p&amp;lt;0.001), had higher rates of arterial hypertension (72.5% vs 68.2%, p&amp;lt;0.001), diabetes mellitus (35.6% vs 30.7%, p&amp;lt; 0.001), stroke (9.0% vs 6.6%, p &amp;lt; 0.001) and previous haemorrhage (p= 0.004). No statistically significant differences regarding previous MI (p= 0.240). Hb levels &amp;lt;8g/dL (8.1% vs 0.6%, p&amp;lt;0.001) were associated with a higher risk of hemorrhagic events but not lower levels of Plat, instead higher levels (&amp;gt; 450x109/L) were event associated (1.8% vs 0.9%, p&amp;lt;0.001). The choice of femoral access was related to an increased risk of hemorrhagic events (p&amp;lt;0.001). Logistic regression confirmed that the Hb levels &amp;lt; 12g/dL when compared with normal levels were related to the composite endpoint proportionally to the degree of anemia, the lower the level of Hb the more likely these events occur, Hb &amp;lt;8g/dL p&amp;lt;0.001, OR 4.02, CI (95%) 2.50-6.47 and Hb 8-12g/dL, p&amp;lt;0.001, OR 0.761, CI (95%) 0.693-0.837. Survival analysis also showed that cardiovascular (CV) mortality and re-admission at 1 year were related to the degree of anemia. Conclusion Lower levels of Hb correlated well and proportionally to the occurrence of the composite endpoint as well as cardiovascular (CV) mortality and re-admission at 1 year. Contrarily to expected lower levels of Plat did not correlate with a higher risk of hemorrhagic events but instead thrombocytosis did, as a paradoxical risk of bleeding has been noted in patients with thrombocytosis, especially extreme thrombocytosis.

Left ventricular unloading during venoarterial extracorporeal membrane oxygenation implantation: benefits or complications?

Abstract Funding Acknowledgements None. Introduction Peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) is a therapeutic option for refractory cardiogenic shock (CS). However, the retrograde flow increases afterload, leading to pulmonary edema, blood stasis in the left ventricle (LV) and formation of thrombi. Several strategies try to reduce LV pressure, including the percutaneous transvalvular microaxial pump (p-MCS) and intra-aortic balloon pump (IABP). However, these interventions are associated to complications, such as limb ischemia, embolism, bleeding and hemolysis. Purpose This study aims to investigate whether simultaneous LV unloading at ECMO implant yields clinical benefits or complications compared to ECMO implantat alone. Methods Consecutive patients (pts) with CS requiring peripheral VA ECMO from January 2020 to August 2023 were prospectively included, comparing the group that received LV unloading through IABP or p-MCS to the group that received ECMO only. Standard statistical methods were used. Results A total of 38 pts required VA ECMO. 18 of them received LV unloading since cannulation (8 with IABP and 10 with p-MCS). In the group without initial LV-unloading (20), 3 pts required IABP and 1 p-MCS during support and 1 was changed to VAV ECMO. Change to axillar configuration was perfomed in 1 pts in the unloaded group and in 2 in the only-ECMO group. A higher prevalence of SCAI E (72.2%) was observed in the unloaded-ECMO, compared to the only-ECMO, where SCAI D was more prevalent (60%) (p=0.024). In the LV unloaded group, acute myocardial infarction (AMI) was the leading cause of CS, while myocarditis was the predominant one in the other group (p=0.01). The simultaneous support had a higher rate of intubation (94.4% vs 50% p=0.004) and more acute pulmonary edema (44.4% vs 10% p=0.027). In the ECMO-only 2 pts required intubation during support and LV stasis was observed in 1, whereas no cases were reported in the LV-unloaded group (p=0.036). The mean PaO2/FiO2 during support were higher in the not unloaded group (284.54 vs 200.50 mmHg p=0.036), necessitating lower FiO2 levels (40.89 vs 61.47% p=0.003). In terms of complications, we included the 4 patients from the ECMO-only group who eventually required LV unloading in the unloaded-ECMO. There were no significant differences in the duration of support, in-hospital mortality, stroke, embolism, systemic and local bleeding, or hemolysis. Conclusions Pts with ECMO and LV unloading since cannulation debuted with more severe CS, more AMI as the underlying cause, higher rates of acute pulmonary edema, and intubation. Despite these challenges, they did not experience worse outcomes in terms of in-hospital mortality or ischemic and hemorrhagic events. Notably, 4 patients initially managed with ECMO eventually required subsequent LV unloading. Consequently, the simultaneous implantation of ECMO and a LV unloading device appears to be a reasonable alternative for select patients with a higher risk profile.

STEMI antiplatelet pretreatment strategy - national multicenter registry experience

Abstract Funding Acknowledgements None. Background/Introduction Antiplatelet therapy is the cornerstone treatment for ST-segment elevation myocardial infarction (STEMI). Dual antiplatelet therapy (DAPT) including aspirin and a potent P2Y12 inhibitor (P2Y12i) is recommended as the default strategy. However, the timing of DAPT remains controversial: European Cardiology Society (ESC) guidelines ceased recommending pretreatment with P2Y12i in STEMI, based on ATLANTIC trial results. Purpose This study aims to evaluate the effect of DAPT with potent P2Y12i pretreatment DAPT in STEMI patients, comparing with DAPT with clopidogrel and aspirin only pretreatment. Methods We have analyzed the antiplatelet pretreatment strategy results of a retrospective cohort of 2283 STEMI patients, from a multicenter national registry, from 2011 till 2019. We compared 3 groups: DAPT with potent P2Y12i, DAPT with clopidogrel and aspirin only. Primary endpoints were death, major adverse cardiovascular events (MACE), including reinfarction, heart failure, sustained ventricular arrhythmia, cardiogenic shock, mechanical complication and stroke, and successful PCI. Safety endpoint was major hemorrhagic events between different strategies. Results A total of 2283 STEMI patients where included, with a mean age of 66±13 years and 27% (n=627) were female. The population was divided in 3 groups, according with pretreatment strategy: DAPT with potent P2Y12i, DAPT with clopidogrel and aspirin only. 334 patients undergone DAPT with potent P2Y12i, and 86% (n=296) had a successful PCI, 21% (n=69) had a MACE and 9% (n=31) died in hospital. The group of patients submitted to DAPT with clopidogrel were 1815, and 80% (n=1448) had a successful PCI, 29% (n=527) had a MACE and 11,5% (n=209). The group pretreated only with aspirin were 124 patients, of which, only 14% (n=17) had a successful PCI, 38% (n=47) had a MACE and 39% (n=49) died. Regarding safety outcomes, 1,5% (n=5) patients with DAPT with potent P2Y12i had a significant hemorrhage, comparing with 3% (n=53) of patients with DAPT with clopidogrel and 3% (n=4) of aspirin only group of patients. There was a statistically significant higher rate of successful PCI with DAPT with potent P2Y12i (p&amp;lt;0,05 OR 2), a statistically significant lower number of MACE (p&amp;lt;0,05 OR 0,6) and in hospital deaths (p=0,04 OR 0,67), comparing with DAPT with clopidogrel and aspirin only groups. There was no statistically significant difference between groups in terms of hemorrhagic events (p=0,7). According to our retrospective multicenter national registry, pretreatment with potent P2Y12i is associated with better results, namely higher rate of successful PCI, less MACE and in hospital death, contrary to recent trials. Our study has some bias: the pretreatment with DAPT was standard of care during the registry, and the choice for aspirin only strategy might be due to higher risk patients, as the choice was not randomized.Antiplatelet treatment comparison

Characteristics, management and prognosis of patients with coronary artery disease undergoing coronary intervention and atrial fibrillation

Abstract Funding Acknowledgements None. Introduction The selection of antithrombotic treatment in patients with ischaemic heart disease (IHD) and atrial fibrillation (AF) represents a challenge when trying to balance ischaemic and haemorrhagic risk. However, there is little "real-life" data on the selected antithrombotic treatment and its short and long-term prognosis. Methods A Prospective multicentre study that includes patients with IHD [acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] and AF admitted to 13 Spanish centres. The objective is to describe the characteristics, antithrombotic treatment and prognosis of patients undergoing PCI and AF. Results 373 patients were included. The average age was 77.6 ± 9.8 years (28% women). Patients had a high ischaemic and haemorrhagic risk [CHA2DS2VASc 4 (2-5) and HASBLED 3 (2-4)], with 25.5% being frail according to the Clinical Frailty Scale. The main reason for admission was ACS (44.8% NSTEMI, 22.2% STEMI and 33% CCS ), and 49.8% of patients had multivessel disease. 70.3% of patients underwent revascularisation, mainly percutaneously (92.2%). Among those percutaneously revascularised, the most used antithrombotic treatment was triple therapy with double antiplatelet therapy (DAPT) + oral anticoagulant (OAC) (62.5%), followed by double therapy with monoantiplatelet therapy + OAC (29.2%). In revascularised patients over 80, the most selected antithrombotic therapy was similar: 60.5% and 28.9%, respectively. The most used OAC was apixaban (42.3%), followed by vitamin K antagonists (17.3%). One-year survival was 88.5%. 2.6% of patients presented an ischemic stroke, and 4.8% suffered a new ACS. At the same time, haemorrhagic events (BARC ≥2) were 8.9%. Conclusions A high ischaemic and haemorrhagic risk co-exists in patients with IHD and AF. In our setting, triple therapy, mainly with the use of DOACs over VKA, is the preferred therapy. The long-term mortality of this subgroup of patients with IHD is high (&amp;gt;10%), with a rate of haemorrhagic events (8.9%) higher than ischaemic events (4.8%).Characteristics of patients