Intracranial Hemorrhage In Patients Research Articles

FGF21 alleviates endothelial mitochondrial damage and prevents BBB from disruption after intracranial hemorrhage through a mechanism involving SIRT6

BackgroundDisruption of the BBB is a harmful event after intracranial hemorrhage (ICH), and this disruption contributes to a series of secondary injuries. We hypothesized that FGF21 may have protective effects after intracranial hemorrhage (ICH) and investigated possible underlying molecular mechanisms.MethodsBlood samples of ICH patients were collected to determine the relationship between the serum level of FGF21 and the Δ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\Delta$$\\end{document}GCS%. Wild-type mice, SIRT6flox/flox mice, endothelial-specific SIRT6-homozygous-knockout mice (eSIRT6−/− mice) and cultured human brain microvascular endothelial cells (HCMECs) were used to determine the protective effects of FGF21 on the BBB.ResultsWe obtained original clinical evidence from patient data identifying a positive correlation between the serum level of FGF21 and Δ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\Delta$$\\end{document}GCS%. In mice, we found that FGF21 treatment is capable of alleviating BBB damage, mitigating brain edema, reducing lesion volume and improving neurofunction after ICH. In vitro, after oxyhemoglobin injury, we further explored the protective effects of FGF21 on endothelial cells (ECs), which are a significant component of the BBB. Mitochondria play crucial roles during various types of stress reactions. FGF21 significantly improved mitochondrial biology and function in ECs, as evidenced by alleviated mitochondrial morphology damage, reduced ROS accumulation, and restored ATP production. Moreover, we found that the crucial regulatory mitochondrial factor deacylase sirtuin 6 (SIRT6) played an irreplaceable role in the effects of FGF21. Using endothelial-specific SIRT6-knockout mice, we found that SIRT6 deficiency largely diminished these neuroprotective effects of FGF21. Then, we revealed that FGF21 might promote the expression of SIRT6 via the AMPK–Foxo3a pathway.ConclusionsWe provide the first evidence that FGF21 is capable of protecting the BBB after ICH by improving SIRT6-mediated mitochondrial homeostasis.

Assessing Donor and Platelet Transfusion Characteristics on Intracranial Hemorrhage Outcomes

Introduction: Intracranial hemorrhage (ICH) patients require rapid treatment to reverse coagulopathy, which can help establish hemorrhage control and improve outcomes. While acute platelet transfusions are given in ICH to reverse platelet dysfunction, delays in administration of hemorrhage control therapies and platelet unit characteristics themselves may impact the efficacy and clinical outcomes in different patient populations. Thus, we sought to evaluate the relationship of platelet transfusion timing and platelet unit characteristics with ICH mortality. Methods: Available data for incident hospitalizations of adult ICH patients between 2019-2022 from 3 of the 5 participating sites within the multicenter REDS-IV-P network were assessed. ICH patients were included if they received ≥ 1 acute platelet transfusion within 48 hours of admission and presented with one of the following ICH etiologies: trauma (tICH), spontaneous intracerebral hemorrhage (sICH), and aneurysmal subarachnoid hemorrhage (aSAH). Patients with early withdrawal of care and death within the first 48 hours were excluded. Separate logistic regression models (each adjusting for age, sex, race/ethnicity, comorbidities, and number of platelet transfusions) assessed the relationship of 30 day ICH mortality outcome with the following: a) time to initial platelet transfusion in hour quartiles: <2.7 hours [reference] vs 2.7-5.6 hours vs 5.7-14.5 hours vs 14.6-48 hours, b) any major ABO incompatible platelet transfusion versus identical or minor mismatch, and c) any donor-recipient sex mismatched platelet transfusion. Separate subgroup analyses were performed by ICH etiologic subgroups. Results: Amongst 619 ICH patients receiving an acute platelet transfusion, 52% were from tICH, 36% from sICH, and 12% from aSAH. Mortality was seen in 17% of the overall cohort. Longer times to platelet transfusion (longest quartile: 14.6-48 hours) were associated with mortality in the overall ICH cohort (adjusted OR 2.12; 95%CI: 1.10-4.12). In sICH, effect size estimates were notably greater with the longest quartile time to platelet transfusion also being associated with mortality (adjusted OR 4.66; 95%CI: 1.58-14.8). Longer times to platelet transfusion were not associated with mortality in tICH (adjusted OR 1.19; 95%CI: 0.45-3.15). Amongst 543 ICH patients with available donor-recipient ABO data, 32% received a major ABO incompatible platelet transfusion. While there was not an association of major ABO incompatible platelet transfusion with mortality in the overall cohort (adjusted OR 1.41; 95%CI 0.82-2.40), there again was a significant association of this exposure with mortality in the sICH subgroup (adjusted OR 3.06; 95%CI: 1.22-7.90). No associations of major ABO incompatible platelet transfusions were identified in tICH subgroup (adjusted OR 1.02; 95%CI: 0.49-2.10). We did not identify a relationship of sex mismatched platelet units with mortality in the overall ICH cohort or in any ICH subgroups. Conclusions: In our analyses of data available from the REDS-IV-P network, we identified a suggestive relationship between longer times to platelet transfusion and mortality, but not of ABO mismatch in our overall ICH cohort. However, sICH may be a specific ICH subgroup more vulnerable to platelet transfusion characteristics and practices, particularly time to platelet transfusion and major ABO incompatible platelet unit exposures. Further work is necessary to assess the generalizability of our data and to clarify whether certain adult ICH patients require specially tailored platelet transfusion approaches.

Thrombosis and Intracranial Hemorrhage in Patients with Metastatic Brain Cancer Treated with Immune Checkpoint Inhibitors Versus Chemotherapy

Background Metastatic brain cancer increases the risk of thrombosis and intracranial hemorrhage (ICH). Immune Checkpoint Inhibitors (ICI) have emerged as breakthrough therapies for the treatment of metastatic disease. Thrombosis has been increasingly reported as a potential adverse event associated to ICI treatment. There is conflicting evidence on the comparative risk of thrombosis between ICI and chemotherapy, and limited data on bleeding outcomes during ICI treatment. We aimed to compare the rate of thrombosis and ICH in patients with metastatic brain tumors treated with ICI versus chemotherapy. Methods A retrospective, single-center cohort study was performed at Beth Israel Deaconess Medical Center. Patients with metastatic brain tumors, treated from 2010 to 2020 with ICI or chemotherapy were included. Primary endpoints included development of thrombotic and ICH events within 12 months of starting treatment. Thrombotic events included venous thromboembolism (VTE), or arterial thrombosis confirmed by imaging. ICH events were classified by a neuro-oncologist blinded to patient information. Intracranial bleeding due to surgical interventions or radiation therapy were excluded. Primary exposure was treatment group, defined as ICI with or without chemotherapy compared to chemotherapy alone. Proportions were compared using Chi square or Fisher's exact tests. Log-binomial regression was used to estimate relative risk (RR) and 95% confidence interval (CI) associated with each additional point of the Khorana score (KS). Cox hazard models were used to calculate the hazard of thrombosis and ICH in each group, accounting for death as a competing risk. Models were weighted by the inverse probability of treatment, estimated using age, gender, cancer, KS, elevated creatinine, and prior exposure to anticoagulants and/or antiplatelets (AC/AP) as covariates; weighting (IPTW) to calculate the cumulative incidence (CumI) of thrombosis and ICH among treatment groups, and stratified by use of AC/AP at the start of treatment. Results We included 264 patients with a median age of 65.4 years (Table 1). Overall, 59.8% were female. Major primary malignancies included non-small cell lung cancer (NSCLC) 189 (71.6%), SCLC 31 (11.7%), melanoma 13 (4.9%), and renal cell carcinoma 13 (2.9%). Regarding treatment, 78 (29.5%) patients received ICI, and 186 (70.5) chemotherapy; within the ICI group, 65.4% of patients also received chemotherapy. Overall, 28 patients developed thrombotic events, 14 pulmonary embolisms (50%), followed by lower extremity VTE (35.7%). Ten patients developed ICH during the study period, including three patients with major bleeds (>10cm3 in size and/or symptomatic). The majority of bleeding events were noted to be intraparenchymal (80%). The 12-month weighted CumI of thrombosis was similar in the ICI (11.1%, 95%CI 4.5-17.3) and chemotherapy (9.2%, 95%CI 5.6-12.6) groups. The 12-month CumI of ICH was also similar between ICI (7.2%, 95%CI 1.7-12.4) and chemotherapy (8.9%, 95%CI 5.4-12.3) groups. (Figure 1) Median time (MT) to thrombosis was comparable for patients on ICI (58.5 days, IQR26.0-239) and chemotherapy (64.5 days, IQR 26.0-154) (P=1.00). Conversely, ICH occurred earlier in the chemotherapy group (MT 49.0 days, IQR 12-112) compared to the ICI group (MT 280 days, IQR 266-292) (P=0.01). In weighted competing risk models, the hazard of thrombosis was similar among both treatment groups (aHR: 1.05, 95% CI: 0.5-2.1). The risk of ICH was not significantly lower with ICI compared to chemotherapy (aHR: 0.66, 95% CI 0.2-1.5). Within the ICI group, AC/AP use was not associated with significant difference in thrombotic risk (aHR: 0.63, 95%CI 0.1-2.3) but there was a significantly increased risk of ICH (aHR: 9.0, 95%CI 1.0-79.3). Within the chemotherapy group, use of AC/AP was not associated with increased risk of thrombosis (aHR: 0.96, 95%CI 0.3-2.5) or ICH (aHR: 0.16, 95% CI 0.0-1.0). Conclusions Rates of thrombosis and ICH were high in patients with metastatic brain tumors treated with ICI or cytotoxic chemotherapy but did not differ significantly between the two treatment groups. In our cohort, the time to intracranial bleeding was significantly shorter among those on chemotherapy compared to those on ICI. Contrasting risks of ICH and thrombosis in patients with metastatic brain cancer should be considered during treatment.

NCOG-17. RETROSPECTIVE REVIEW OF THE TREATMENT OF VENOUS THROMBOEMBOLISM IN GLIOBLASTOMA PATIENTS RECEIVING BEVACIZUMAB

Abstract Patients with malignant gliomas have an inherently high risk of venous thromboembolism (VTE).1 Bevacizumab is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody commonly used in the treatment of recurrent high-grade gliomas and is known to increase the risk of VTE as well as intracranial hemorrhage.2 Anticoagulation (AC) for VTE also increases the risk intracranial hemorrhage in patients with malignant brain tumors.3 This makes the treatment of VTE in patients with GBM receiving bevacizumab therapy particularly challenging. Here we completed a single center retrospective chart review of patients with glioblastoma (GBM) treated concurrently with anticoagulation for VTE and bevacizumab therapy. The purpose of this review was to assess the safety of concurrent use of these therapies and to note any statistically significant difference in the incidence of hemorrhagic complications between patients treated with anticoagulation at therapeutic versus prophylactic dosing. METHODS: 144 patients with a diagnosis of high-grade glioma and were treated at UCI from 1/1/2019 through 1/1/2022 were screened for the study. 13 GBM patients on treatment with bevacizumab and concurrent anticoagulation were included. Clinical records of these patients were reviewed for the incidence of intracranial hemorrhage or any clinically significant bleeding. RESULTS: The incidence of ICH in GBM patients on concurrent therapy with bevacizumab and anticoagulation was 7.7% and the incidence of other minor bleeding complications was 7.7%. ICH and other minor bleeding was exclusively seen in patients on therapeutic anticoagulant dosing. No bleeding complications were noted in patients on prophylactic AC dosing. CONCLUSION: There is a risk of ICH in patients receiving both bevacizumab and anticoagulation, however compared to historical data, the incidence reported in our study is less than the incidence of ICH in GBM patients on anticoagulation alone. Our study suggests that it is relatively safe to treat patients with these therapies simultaneously.

Predictors of intracranial hemorrhage in neonatal patients on extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) is a life-supportive treatment in neonatal patients with refractory lung and/or heart failure. Intracranial hemorrhage (ICH) is a severe complication and reliable predictors are warranted. The aims of this study were to explore the incidence and possible predictors of ICH in ECMO-treated neonatal patients. We performed a single-center retrospective observational cohort study. Patients aged ≤ 28 days treated with ECMO between 2010 and 2018 were included. Exclusion criteria were ICH, ischemic stroke, cerebrovascular malformation before ECMO initiation or detected within 12 h of admission, ECMO treatment < 12 h, or prior treatment with ECMO at another facility > 12 h. The primary outcome was a CT-verified ICH. Logistic regression models were employed to identify possible predictors of the primary outcome. Of the 223 patients included, 29 (13%) developed an ICH during ECMO treatment. Thirty-day mortality was 59% in the ICH group and 16% in the non-ICH group (p < 0.0001). Lower gestational age (p < 0.01, odds ratio (OR) 0.96; 95%CI 0.94–0.98), and higher pre-ECMO lactate levels (p = 0.017, OR 1.1; 95%CI 1.01–1.18) were independently associated with increased risk of ICH-development. In the clinical setting, identification of risk factors and multimodal neuromonitoring could help initiate steps that lower the risk of ICH in these patients.

Abstract 15203: Periprocedural Oral Anticoagulation for Ventricular Tachycardia Ablation and Postprocedural Stroke - Analysis of a Japanese Nationwide Inpatient Database

Introduction: The effectiveness and the safety of periprocedural anticoagulation for ventricular tachycardia (VT) ablation remain to be clarified. Hypothesis: Periprocedural anticoagulation reduces the incidence of ischemic stroke after VT ablation without increasing intracranial hemorrhage. Methods: Using the Japanese Diagnosis Procedure Combination database, we identified patients aged ≥18 years who underwent VT ablation from July 2010 to March 2021. The endpoints were ischemic stroke and intracranial hemorrhage which occurred during the hospitalization of the index VT ablation or led to re-admissions within three months. We performed weighted analyses using inverse probability of treatment based on propensity-score to adjust for confounding factors. We also conducted analyses stratified by antiplatelet use. Results: We identified 18,894 patients from 750 hospitals who underwent VT ablation (12,918 males [68%], 60.5 ± 15.7 years). Postprocedural ischemic stroke and intracranial hemorrhage were documented in 84 (0.44%) and 15 (0.08%) cases, respectively. Anticoagulants and antiplatelets were administered in 4352 (23.0%) and 5319 (28.2%) patients, respectively. Propensity score-weighted analysis demonstrated no significant association between anticoagulant use and postprocedural ischemic stroke (odds ratio, 0.91; 95% confidence interval [CI], 0.51-1.63; P=0.76). Anticoagulation was also not associated with intracranial hemorrhage (odds ratio, 2.15; 95% CI, 0.65-7.15; P=0.21). In the stratified analysis, anticoagulation was associated with an increased risk of intracranial hemorrhage in patients with antiplatelets (odds ratio, 6.30; 95% CI, 1.26-31.5; P=0.025) but not in those without. Conclusions: Our analysis of Japanese patients who underwent VT ablation suggests that periprocedural administration of anticoagulants may not result in a reduction of ischemic strokes and that adding anticoagulants to antiplatelet therapy may increase the risk of intracranial hemorrhage. Further studies are warranted to investigate the clinical efficacy of periprocedural anticoagulation strategy after VT ablation.

Comparison of direct oral anticoagulants versus low-molecular-weight heparin in primary and metastatic brain cancers: a meta-analysis and systematic review

BackgroundThe safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known. ObjectivesTo conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs low-molecular-weight heparin (LMWH). MethodsA literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n = 1638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup. ResultsThe pooled RR for ICH in patients receiving DOACs vs those receiving LMWH was 0.65 (95% CI, 0.36-1.17; P = .15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = .003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with the type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = .80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants. ConclusionThe risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

Neurological Complications Associated with Hereditary Bleeding Disorders.

Hereditary bleeding disorders may have a wide variety of clinical presentations ranging from mild mucosal and joint bleeding to severe central nervous system (CNS) bleeding, of which intracranial hemorrhage (ICH) is the most dreaded complication. In this review, we will discuss the pathophysiology of specific hereditary bleeding disorders, namely, hemophilia A, hemophilia B, and von Willebrand disease (vWD); their clinical manifestations with a particular emphasis on neurological complications; a brief overview of management strategies pertaining to neurological complications; and a review of literature guiding treatment strategies. ICH is the most significant cause of morbidity and mortality in patients with hemophilia. Adequate control of bleeding with the administration of specific factors or blood products, identification of risk factors for bleeding, and maintaining optimal coagulant activity are essential for appropriately managing CNS bleeding complications in these patients. The administration of specific recombinant factors is tailored to a patient's pharmacokinetics and steady-state levels. During acute bleeding episodes, initial factor activity should be maintained between 80 and 100%. Availability of monoclonal antibody Emicizumab has revolutionized prophylactic therapies in patients with hemophilia. Management of ICH in patients with vWD involves using plasma-derived factor concentrates, recombinant von Willebrand factor, and supportive antifibrinolytic agents individualized to the type and severity of vWD. Hemophilia and vWD are the most common hereditary bleeding disorders that can predispose patients to life-threatening CNS complications-intracranial bleeds, intraspinal bleeding, and peripheral nerve syndromes. Early care coordination with a hematologist can help develop an effective prophylactic regimen to avoid life-threatening bleeding complications in these patients. Further research is needed to evaluate using emicizumab as an on-demand treatment option for acute bleeding episodes in patients with hemophilia.

Incidence of Intracranial Hemorrhage in Patients Younger Than 2 Months Receiving Sodium Bicarbonate 4.2% vs 8.4.

To assess the incidence of intracranial hemorrhage (ICH), including intraventricular hemorrhage, in infants receiving 4.2% or 8.4% sodium bicarbonate. This is a single-center retrospective chart review of neonates and infants with a gestational age (GA) >32 weeks and a postnatal age <2 months who received sodium bicarbonate in an intensive care unit at an academic tertiary children's hospital. The primary outcome was the incidence of ICH in patients with baseline and follow-up head imaging. The secondary outcome was the incidence of ICH on follow-up head imaging, with or without baseline head imaging. There were 351 patients screened, with 135 meeting inclusion criteria. Of these, 84% were born ≥37 weeks GA. Forty-two met the criteria for the primary outcome. Study participants were further subdivided into 3 groups based on the concentration of sodium bicarbonate received: only 4.2%, only 8.4%, or a mixed group that received at least 1 dose each of 4.2% and 8.4%. Intracranial hemorrhage was noted in 1 patient in each group: 8.3%, 5.6%, and 8.3%, respectively (p = 1.00). For the secondary outcome, 11 ICHs were seen on head imaging: 11.3%, 3.8%, and 10%, respectively. There was no statistically significant difference in the incidence of ICH (p = 0.325). The incidence of ICH in term neonates and infants was not significantly different in those receiving 4.2% vs 8.4% sodium bicarbonate. Although additional studies are needed, this study suggests it may be possible to safely expand the use of 8.4% in neonates/infants ≥37 weeks GA. These results should not be applied to preterm neonates (<37 weeks GA and/or <1500 g) or neonates with additional ICH risk factors.

PB0960 Thrombosis and Intracranial Hemorrhage in Patients with Metastatic Brain Tumors Treated with Immune Checkpoint Inhibitors

PB0960 Thrombosis and Intracranial Hemorrhage in Patients with Metastatic Brain Tumors Treated with Immune Checkpoint Inhibitors

Increased Neuron-Specific Enolase Level Predicts Symptomatic Intracranial Hemorrhage in Patients with Ischemic Stroke Treated with Endovascular Treatment

Neuron-specific enolase (NSE), which is a highly specific marker for neurons, could be a predictor for prognosis in patients with symptomatic intracranial hemorrhage (sICH) with acute ischemic stroke who are receiving endovascular treatment (EVT). This study aimed to investigate the relationship between NSE and sICH in patients with acute anterior circulation stroke undergoing EVT. A total of 215 consecutive patients with acute stroke treated with EVT were included. Patients with stroke and acute anterior circulation occlusion, receiving EVT treated at our hospital, were enrolled between January 2017 and August 2021. NSE level was measured on arrival at the neurology intensive care unit after EVT. The patients were divided into 2 groups according to whether sICH was present. Univariate and multivariate analyses were performed. NSE level was also incorporated into the TAG score (modified Thrombolysis in Cerebral Infarction score, Alberta Stroke Program Early CT Score, and glucose level), which was developed as a scoring system to predict sICH, and the prediction capability was compared with the TAG score alone. Causal inference was performed using the package DoWhy in Python to evaluate the causal relationship between NSE and sICH. The area under the curve (AUC) value of NSE showed moderate accuracy, with an AUC value of 0.729 (95% confidence interval, 0.655-0.795; P < 0.001). The NSE cutoff value was set at 23.88 ng/mL. When the NSE level ≥23.88 ng/mL, the sensitivity was 58.33% and the specificity was 78.72% (P < 0.001). The AUC for the TAG+ NSE score was 0.801 compared with an AUC of 0.632 for the TAG score (Z= 2.034; P= 0.042). A causal inference model using the DoWhy library shows a proportional relationship between NSE and the diagnosis of sICH. This study is the first to show that increased NSE level is an independent predictor of sICH in patients with acute anterior circulation stroke who are undergoing endovascular treatment.

Association of serum occludin levels and perihematomal edema volumes in intracranial hemorrhage patients.

Perihematomal edema (PHE) is one of the severe secondary damages following intracranial hemorrhage (ICH). Studies showed that blood-brain barrier (BBB) injury contributes to the development of PHE. Previous studies showed that occludin protein is a potential biomarker of BBB injury. In the present study, we investigated whether the levels of serum occludin on admission are associated with PHE volumes in ICH patients. This cross-sectional study included 90ICH patients and 32 healthy controls.The volumes of hematoma and PHE were assessed using non-contrast cranial CT within 30 min of admission. Blood samples were drawn on admission, and the levels of baseline serum occludin were detected using enzyme-linked immunosorbent assay. Partial correlation analysis and multiple linear regression analysis were performed to evaluate the association between serum occludin levels and PHE volumes in ICH patients. The serum occludin levels in ICH patients were much higher than health controls (median 0.27 vs. 0.13 ng/mL, p < 0.001). At admission, 34 ICH patients (37.78%) had experienced a severe PHE (≥30 mL), and their serum occludin levels were higher compared to those with mild PHE (<30 mL) (0.78 vs. 0.21 ng/mL, p < 0.001). The area under the receiver operating characteristics curve (ROC) of serum occludin level in predicting severe PHE was 0.747 (95% confidence interval CI 0.644-0.832, p < 0.001). There was a significant positive correlation between serum occludin levels and PHE volumes (partial correlation r = 0.675, p < 0.001). Multiple linear regression analysis showed that serum occludin levels remained independently associated with the PHE volumes after adjusting other confounding factors. The present study showed that serum occludin levels at admission were independently correlated with PHE volumes in ICH patients, which may provide a biomarker indicating PHE volume change.

Effect of edaravone on symptomatic intracranial hemorrhage in patients with acute large vessel occlusion on apixaban for non-valvular atrial fibrillation

BackgroundEdaravone administration was associated with lower incidence of symptomatic intracranial hemorrhage (sICH) in patients with acute large vessel occlusion (LVO). However, its protective effect on sICH in patients with LVO who receive direct oral anticoagulants for non-valvular atrial fibrillation (NVAF) is uncertain. ObjectivesTo explore the effect of edaravone administration on the incidence of sICH in patients with acute LVO receiving apixaban for NVAF. MethodsA Japanese multicenter registry of apixaban on clinical outcome of the patients with LVO or stenosis (ALVO study) included patients who were admitted within 24 h after stroke onset and were received apixaban within 14 days of stroke onset. Patients were divided into two groups according to edaravone administration (Edaravone and No-Edaravone groups). The incidence of sICH within one year and infarct growth before apixaban administration were compared between these groups. ResultsOf the 686 enrolled patients, 622 were included and edaravone was administered to 407 (65.4%). The incidences of sICH in Edaravone and No-Edaravone groups were 1.3% and 5.0%, respectively (p = 0.01). The inverse probability of treatment-weighting (IPTW) hazard ratio (HR) (95% confidence interval [CI]) of Edaravone group for sICH within one year was 0.36 (0.15–0.80) compared to No-Edaravone group. The incidences of infarct growth in Edaravone and No-Edaravone groups were 35.3% and 42.0%, respectively (p = 0.13). IPTW HR (95% CIs) for infarct growth was 0.76 (0.60–0.97). ConclusionsEdaravone administration was associated with a lower incidence of sICH in patients with LVO and NVAF who administrated apixaban.

Hemorrhage Risk in Moyamoya Disease with Fetal-Type Posterior Cerebral Artery: A Propensity Score-Matched Analysis

Patients with moyamoya disease (MMD) and fetal-type posterior cerebral arteries have not been thoroughly investigated as yet. We focused on the risk of intracranial hemorrhage in patients with MMD and fetal-type posterior cerebral arteries. We reviewed 2422 patients with MMD diagnosed at the Neurosurgical Department of Beijing Tiantan Hospital between May 2009 and December 2020. We classified patients into 2 groups according to whetherthey had a fetal-type posterior cerebral artery. After 1:1 propensity score matching, hemorrhagic tendencyand Suzuki stage were compared between patients with a fetal-type posterior cerebral artery (group I) and patients without a fetal-type posterior cerebral artery (group II). In total, 2415 patients were included in this study; 181 had fetal-type posterior cerebral arteries. Hemorrhagic events were more frequently observed in patients with fetal-type posterior cerebral artery development than in those without it (28.2% vs. 18.8%, P=0.035). However, Suzuki stages did not differ between the 2 matched groups (4.03 vs. 4.20, P= 0.081). Hemorrhagic events occurred more frequently in patients with MMD with fetal-type posterior cerebral arteries than in those without.

P11.69.B INTRAVENOUS THROMBOLYSIS WITH OR WITHOUT ENDOVASCULAR TREATMENT FOR SUSPECTED ISCHEMIC STROKE IN PATIENTS WITH INTRACRANIAL TUMORS

Abstract BACKGROUND: AND OBJECTIVES Intravenous thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) is scarce. METHODS In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration. RESULTS Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT, among them 29 patients (28%) with additional endovascular treatment, with suspected, i.e. imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in nine and four patients (9% and 4%). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in six and three patients (7% and 4%). In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was one symptomatic nonfatal ICH (6%). Out of four patients with tumors of the pituitary region, two patients (50%) had symptomatic ICH including one fatal ICH (25%). Tumor size was not associated with occurrence of symptomatic ICH (Odds ratio 2.8, 95% CI 0.3-24.8, p=0.34). CONCLUSION In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort appear to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.

Trends and predictors of intracranial hemorrhage in patients with advanced heart failure on left ventricular assist device from 2005 to 2014 in the United States

ObjectivesLeft ventricular assist devices are known to extend survival in patients with advanced heart failure; however, their association with intracranial hemorrhage is also well-known. We aimed to explore the risk trend and predictors of intracranial hemorrhage in patients with left ventricular assist devices. Material and MethodsWe included patients aged 18 years or older with left ventricular assist devices hospitalized in the US from 2005 to 2014 using the National Inpatient Sample. We computed the survey-weighted percentages with intracranial hemorrhage across the 10-year study period and assessed whether the proportions changed over time. Predictors of intracranial hemorrhage were evaluated using multivariable logistic regression model. ResultsOf 33,246 hospitalizations, 568 (1.7%) had intracranial hemorrhage. The number of left ventricular assist devices placements increased from 873 in 2005 to 5175 in 2014. However, the risk of intracranial hemorrhage remained largely unchanged (1.7% to 2.3%; linear trend, P = 0.604). The adjusted odds of intracranial hemorrhage were increased with the presence of one of the following variables: female sex (odds ratio [OR], 1.58; 95% CI, 1.03-2.43), history of ischemic stroke (OR, 3.13; 95% CI, 1.86-5.28), or Charlson Comorbidity Index score of 3 or more (OR, 77.40; 95% CI, 10.03-597.60). ConclusionsOver the last decade, the risk of intracranial hemorrhage has remained relatively unchanged despite an increase in the use of left ventricular assist devices in patients with advanced heart failure. Women, higher Charlson Comorbidity Index scores, and history of ischemic stroke were associated with higher odds of intracranial hemorrhage in patients with left ventricular assist devices.

Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries.

An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). An externally validated model improves ICH risk stratification. Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Clinical characteristics and risk factors of intracranial hemorrhage after spinal surgery.

Intracranial hemorrhage after spinal surgery is a rare and devastating complication. To investigate the economic burden, clinical characteristics, risk factors, and mechanisms of intracranial hemorrhage after spinal surgery. A retrospective cohort study was conducted from January 1, 2015, to December 31, 2022. Patients aged ≥ 18 years, who had undergone spinal surgery were included. Intracranial hemorrhage patients were selected after spinal surgery during hospitalization. Based on the type of spinal surgery, patients with intracranial hemorrhage were randomly matched in a 1:5 ratio with control patients without intracranial hemorrhage. The patients' pre-, intra-, and post-operative data and clinical manifestations were recorded. A total of 24472 patients underwent spinal surgery. Six patients (3 males and 3 females, average age 71.3 years) developed intracranial hemorrhage after posterior spinal fusion procedures, with an incidence of 0.025% (6/24472). The prevailing type of intracranial hemorrhage was cerebellar hemorrhage. Two patients had a poor clinical outcome. Based on the type of surgery, 30 control patients were randomly matched in 1:5 ratio. The intracranial hemorrhage group showed significant differences compared with the control group with regard to age (71.33 ± 7.45 years vs 58.39 ± 8.07 years, P = 0.001), previous history of cerebrovascular disease (50% vs 6.7%, P = 0.024), spinal dura mater injury (50% vs 3.3%, P = 0.010), hospital expenses (RMB 242119.1 ± 87610.0 vs RMB 96290.7 ± 32029.9, P = 0.009), and discharge activity daily living score (40.00 ± 25.88 vs 75.40 ± 18.29, P = 0.019). The incidence of intracranial hemorrhage after spinal surgery was extremely low, with poor clinical outcomes. Patient age, previous stroke history, and dura mater damage were possible risk factors. It is suggested that spinal dura mater injury should be avoided during surgery in high-risk patients.

Clinical characteristics and outcomes of patients with intracerebral hemorrhage after acute myocardial infarction

Data regarding patients with intracranial hemorrhage (ICH) following acute myocardial infarction (AMI) is scarce. This study aims to investigate the incidence, clinical characteristics, prevention, treatment, and prognosis of ICH in patients with AMI.Among 5257 patients with AMI, 14 cases (0.27%) experienced ICH following AMI, including 11 males and three females. In-hospital mortality occurred in eight patients (57.1%), all of whom experienced sudden loss of consciousness. Six patients (42.6%) were classified as high or very high risk according to CRUSADE score, and seven patients (50.0%) were classified as high risk according to Academic Research Consortium for High Bleeding Risk (ARC-HBR). The CRUSADE and ARC-HBR scores can complement each other in risk assessment. All in-hospital deaths occurred within four days of ICH onset; The volume of ICH in patients who died in the hospital was significantly higher than in those who survived and were discharged, with 30 ml possibly serving as a threshold.The incidence of ICH following myocardial infarction is low; however, the mortality rate is extremely high, presenting considerable challenges for clinical treatment. Prevention, early detection, and prompt symptomatic management are essential for improving patient outcomes.

Splenic Artery Embolization in a Patient With Intracranial Hemorrhage Due to Refractory Persistent Immune Thrombocytopenia.

Managing intracranial bleeding in patients with refractory immune thrombocytopenia is difficult. A 16-year-old female refractory to prednisolone, intravenous immunoglobulin, eltrombopag, and cyclosporin exhibited heavy menstrual bleeding requiring packed red blood cell transfusions. Autoimmune antibodies were detected, indicating of lupus, and hydroxychloroquine sulfate was administered. In month 6 following the diagnosis, the patient presented with intracranial hemorrhage. Splenic artery embolization promptly increased platelets, and the patient was discharged without any neurological sequela. In month 5 of embolization, the patient's platelet count continued to exceed 300,000/µL without any medical treatment. Splenic artery embolization is a life-saving procedure in refractory immune thrombocytopenia.