History Of Intracranial Hemorrhage Research Articles

Resumption of anticoagulation therapy among Non-Valvular Atrial Fibrillation (NVAF) patients with prior intracranial haemorrhage

Abstract Purpose Resumption of anticoagulation therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF) suffering from intracranial haemorrhage (ICH) is challenging in clinical practice. The aim of this study was to evaluate impact of resumption of OAC on clinical outcomes in NVAF patients with history of ICH. Methods Consecutive patients with NVAF with or without OAC who survived from an index ICH between January 2018 and July 2022 in 16 public hospitals in Hong Kong were identified and analyzed retrospectively. Resumption of OAC was substantiated by new prescription obtained from electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Risks of ischemic stroke, recurrent ICH and all-cause mortality were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC and HASBLED scores. Sub-analysis was conducted to compare outcomes between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference among patients who resumed DOAC or VKA. Results Of 982 patients who met inclusion criteria (mean age 77.7±10.9, female 40.9%), 39.1% (n=384) were OAC naive, 32.2% (n=316) resumed DOAC, 12.6% (n=124) resumed VKA, 9.0% (n=88) discontinued DOAC and 7.1% (n=70) discontinued VKA. During a median follow-up period of 2.0 (IQR: 0.7-3.5) years, no statistically significant difference in risk of ischemic stroke was observed among 5 groups. Discontinuation of DOAC was associated with markedly higher risk of ischemic stroke (aSHR=8.32 (1.8-39.3)) only among AF patients with CHA2DS2VASC score ≥ 4, Risk of recurrent ICH was higher in patients who resumed VKA (aSHR=1.6(1.0-2.5)). Sub-analysis demonstrated resumption of apixaban was associated with lowest risk of recurrent ICH (aSHR=0.6(0.4-0.9)). Compared to OAC naïve patients, those who resumed DOAC (aSHR=0.5(0.4-0.7)) had lowest risk of all-cause mortality, whereas discontinuation DOAC (aSHR=1.9(0.4-2.5) and VKA (aSHR=1.6(0.2-2.2)) were both associated with increased mortality. Conclusion Our real-world data revealed among NVAF patients with prior ICH long term discontinuation of OAC was associated with increased risk of ischemic stroke. Recurrent ICH was highest among patients who resumed VKA and lowest with apixaban.

Impact of early bleeding on long-term mortality after left atrial appendage occlusion

BackgroundShort-term antithrombotic therapy is recommended after left atrial appendage occlusion(LAAO) to reduce the risk of device-related thrombosis(DRT). However, patients referred for LAAO have excess bleeding risk. Yet, short-term bleeding events post-LAAO are not well characterized. ObjectiveWe aimed to evaluate the incidence of early bleeding post-LAAO and its association with long-term mortality risk. We also sought to identify predictors of early bleeding. MethodsPatients who underwent LAAO at Mayo Clinic between 2018 and 2023 were included. Early bleeding was defined as bleeding that occurred within three months of discharge. A multivariable Cox proportional hazards model was used to assess the association between early bleeding and death and to estimate the hazard ratio(HR). Multivariable regression analysis was used to identify predictors of early bleeding. ResultsAmong the 592 patients included, 389(66%) were male, and mean age was 75.6 years. Eighty-three patients(14.0%) experienced early bleeding, with the majority having minimal(63.4%) or minor(17.3%) bleeding. At a median follow-up of 14.4 months(IQR 4.2-27.9), early bleeding after LAAO was associated with an increased risk of all-cause mortality (adjustedHR, 2.07; 95%CI, 1.15-3.75; P=0.02). A history of intracranial bleeding, non-paroxysmal atrial fibrillation, CHA2DS2VASc score, and early DRT were independent predictors of early bleeding. Anti-thrombotic therapy on discharge was not associated with early non-procedural bleeding. ConclusionsOne in seven patients experience a non-procedural bleeding event within 90 days after LAAO. Early bleeding after LAAO is associated with a higher all-cause mortality during mid-term follow-up. Further studies are needed to optimize the management of patients undergoing LAAO.

Left atrial appendage closure for patients with atrial fibrillation at high intracranial haemorrhagic risk

Background and objectivesAlthough left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH), outcome data are scarce. We assessed...

Choice of valve substitutes.

Infective endocarditis often necessitates surgical intervention, and the choice of valve substitute remains a topic of controversy and highly debatable due to the wide range of available options and recent technical advancements. This manuscript reviews the different valve substitutes in the context of infective endocarditis, including mechanical and bioprosthetic valves, homografts, xenografts, and tissue-engineered valves. The patient's age, sex, demographic location, intellectual quotient, comorbidities, available options, and the experience of the surgeon should all be taken into consideration while choosing the best valve substitute for that individual. While valve repair and reconstruction are preferred whenever feasible, valve replacement may be the only option in certain cases. The choice between mechanical and bioprosthetic valves should be guided by standard criteria such as age, sex, expected lifespan, associated comorbidities, and anticipated adherence to anticoagulation therapy and accessibility of medical facilities for follow-up. For patients with severe chronic illness or a history of intracranial bleeding or associated hematological disorders, the use of mechanical prostheses may be avoided. Homografts and bioprosthetic valves provide an alternative to mechanical valves, thereby decreasing the necessity for lifelong anticoagulation after surgery and diminishing the likelihood of bleeding complications. The manuscript also discusses specific valve substitutes for different heart valves (aortic, mitral, pulmonary, tricuspid positions) and highlights emerging techniques such as the aortic valve neocuspidization (Ozaki procedure) and tissue-engineered valves. Ultimately, the ideal valve substitute in IE should be evidence based on a comprehensive elucidation of clinical condition of the patient and available options.

Safety and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with History of Intracranial Hemorrhage within the Florida Stroke Registry (S10.001)

Safety and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with History of Intracranial Hemorrhage within the Florida Stroke Registry (S10.001)

Gender disparities and predictors of in-hospital mortality with Takotsubo cardiomyopathy

BackgroundTakotsubo cardiomyopathy (TCM) is classically associated with significant gender disparities, such that it is more prevalent in females, but the clinical outcomes are worse for male patients. The goal of this study was to assess contemporary gender disparities in clinical outcomes of TCM hospitalizations and to determine predictors of male in-hospital mortality. MethodsThis was a retrospective analysis involving adult hospitalizations for TCM in the U.S between 2016 and 2020. Multivariable Logistic regression was used to estimate Odds Ratio (OR) for in-hospital mortality between the two genders. Univariable Cox regression was performed to identify predictors associated with in-hospital mortality for male hospitalizations. All factors from the univariable analysis with p < 0.20 were included in a multivariable Cox regression model. ResultsA total of 199,920 patients with TCM were identified. Female patients with TCM had 50% lower risk of in-hospital mortality compared to male patients (Adjusted OR 0.50, 95% CI 0.46–0.55, p < 0.001). Older age, higher Charlson comorbidity index, history of intracranial hemorrhage, cardiac arrest, need for vasopressor agents, mechanical intubation, and cardiogenic shock without the use of temporary mechanical circulatory support (MCS) were associated with higher in-hospital male mortality. ConclusionsAlthough TCM is more prevalent among females, gender disparities exist in the clinical outcomes of TCM patients. Cardiac arrest and cardiogenic shock without the use of temporary MCS were found to be the most significant predictors of male in-hospital mortality. Cardiogenic shock with use of temporary MCS did not lead to higher male in-hospital mortality.

A Phase 1 Study of Avapritinib in Combination with Decitabine in Patients with Systemic Mastocytosis with an Associated Hematologic Neoplasm

Background and Rationale: Systemic mastocytosis (SM) is a clonal hematologic neoplasm characterized by abnormal accumulation of mast cells which can lead to symptoms related to mast cell degranulation and/or, in the case of advanced systemic mastocytosis (AdvSM), organ dysfunction due to mast cell infiltration. AdvSM is a category of SM comprised of aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL), and SM with an associated hematologic neoplasm (SM-AHN). Among these, SM-AHN is the most common subtype, accounting for approximately 70% of AdvSM. A KIT D816V mutation found in up to 95% of SM cases is the primary oncogenic driver, making it a key therapeutic target. Avapritinib, a highly potent and selective inhibitor of D816V mutant KIT, has demonstrated high rates of rapid, deep, and durable responses in all AdvSM subtypes, including SM-AHN. However, a recent analysis of the EXPLORER study showed that avapritinib-treated patients were still at risk for progression of the AHN component, despite continued control of mast cell disease burden, indicating that combination therapy is likely to be required for optimal control of SM-AHN due to its inherent molecular complexity. Hypomethylating agents (HMA) form the backbone of therapy for advanced myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN), hematologic neoplasms most likely to co-occur with SM in patients (pts) with SM-AHN. To date, the combination of HMA and KIT inhibitors has not been clinically evaluated. In this study, we aim to assess the safety and tolerability of the combination of avapritinib and decitabine in patients with SM-AHN. Study design: The primary objective of the study is to establish the recommended dose (RP2D) of avapritinib in combination with decitabine based on dose-limiting toxicity, overall safety, and clinical activity data. A dose evaluation steering committee (DESC) comprised of participating investigators will review the totality of safety and efficacy data to determine RP2D. Secondary endpoints include SM overall response rate by the end of 6 cycles by the m-IWG consensus criteria and proposed ECNM-AIM criteria ( Gotlib et al., J Allergy Clin Immunol Pract, 2022), as well as incidence and frequency of adverse events. Exploratory endpoints will consist of patient reported outcomes, progression free survival, overall survival, and correlative biomarkers linked to mast cell disease or AHN. Adult pts with a diagnosis of SM-AHN by the WHO 2022 classification criteria will be eligible for inclusion. Eligible pts must have any of the following myeloid AHN per WHO 2022 criteria: MDS, chronic myelomonocytic leukemia, MDS/MPN with neutrophilia, MDS/MPN with SF3B1 mutation and thrombocytosis, or MDS/MPN- not otherwise specified. Patients with MDS must have intermediate, high- or very-high risk by IPSS-R. Patients with very-low or low-risk MDS by IPSS-R must be intolerant/refractory to ESA or have serum EPO &amp;gt; 200 U/L. A baseline platelet count of ≥ 75 x 10 9/L and ≥ 25 x 10 9/L will be required for inclusion in the dose-finding and the dose-expansion phases, respectively (Figure). Key exclusion criteria include a diagnosis of acute myeloid leukemia, history of intracranial hemorrhage or risk of major hemorrhage, prior treatment with avapritinib or decitabine with documented progression in SM or AHN component, respectively, or history of treatment with alternative KIT inhibitor or azacitidine within 4 weeks of study treatment initiation. In the dose finding part of the study, a Bayesian adaptive design will be employed to assess different doses of avapritinib (50 to 200 mg PO daily) in combination with fixed doses of decitabine (oral decitabine/cedazuridine: 35/100 mg/day or intravenous decitabine: 20 mg/m 2/day on days 1-5) in a 28-day treatment cycle. Close attention will be paid to treatment-emergent thrombocytopenia with protocol-driven treatment holds and dose modification strategies employed when platelet count drops below 50 x 10 9/L. After RP2D is determined, an additional 10 patients will be enrolled in the dose expansion phase. Patients with platelet count ≥ 25 x 10 9/L and &amp;lt; 75 x 10 9/L, will receive lead-in dosing with decitabine or decitabine/cedazuridine with the ability to add avapritinib if sufficient platelet thresholds are achieved. This study will open at 7 sites in the United States and is anticipated to open in January 2024.

Left appendage closure after intracranial hemorrhage: safety, efficacy and timing

Abstract Background Oral anticoagulation (OAC) use increases the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). Left atrial appendage occlusion (LAAO) is an alternative to OAC, however data about its use in patients with prior ICH is scare and the timing of its performance is controversial. Furthermore, the long-term outcomes in this group of patients have not been described. Objective To evaluate the safety and efficacy of LAAO in patients with non-valvular AF and prior ICH (CHA2SVASc &amp;gt;2) and to determine adequate timing of its performance. Methods The sample was obtained from a cohort of 397 patients with AF in which LAAO was performed between 2009 and 2020. In 115 of these patients, the indication for this procedure was ICH (29.8 %). Patients were divided into two groups: early occlusion (n=68; 59%), in which the procedure was performed before 90 days had elapsed after the bleeding, and late occlusion (n=47; 41%), after 90 days. Results Procedure success was 97% globally. Annual incidence of ischemic events was of 0,6%, with an absolute risk reduction of 5,9% and relative risk reduction of 90,3% compared to the predicted risk by CHA2DS2-VASC score. Regarding major hemorrhagic events, annual incidence was of 4%, with an absolute risk reduction of 3,4% and relative risk reduction of 45% compared to the predicted risk by HASBLED score. There were no significant differences between the procedures performed in patients with history of intracranial bleeding and other indications for the procedure. Early closure (first 90 days after the intracranial hemorrhage) was as safe as late closure, without an increase in in-hospital bleedings or complications. Furthermore, long-term follow-up demonstrated a significant reduction in all-cause mortality (11.76% versus 46.8%; HR 0.2, IC95% 0.07-0.55; p&amp;lt;0.001). compared with late occlusion. Conclusions Left atrial appendage occlusion is an effective and safe treatment option to reduce the risk of ischemic stroke in selected patients with AF patients and history of ICH over mean follow-up of 3 years. Early occlusion seems to be at least as safe and effective as late occlusion and therefore could potentially reduce the rate of complications after ICH in selected patients.Survival and closure timingIschemic and bleeding risk reduction

High bleeding risk mainly predicts non-access site bleeding events in the first month after percutaneous coronary intervention

Abstract Background/Introduction The majority of bleeding events after percutaneous coronary intervention (PCI) occur in the first month after PCI. To predict and anticipate on events during hospitalisation and in the first month, the CRUSADE- and ACUITY scores have been developed. In order to enhance the use of bleeding risk stratification, a consortium of PCI centres in the South East of the Netherlands has created and implemented a simple binary variant of the existing models. High bleeding risk (HBR) is defined by one of the following: eGFR&amp;lt; 30; anaemia (Hb &amp;lt; 7mmol/L); a spontaneous bleeding within one year before PCI; a history of intracranial haemorrhage. Purpose We evaluated the predictive value of our risk model and other risk factors for bleeding events in the first month after PCI and discriminated between access site- non-access site bleedings. Methods In an ongoing multicentre prospective PCI registry in the South East of the Netherlands collects baseline and follow-up data of all patients undergoing PCI. We compared access site- and non- access site bleedings between HBR and non HBR using the Kaplan Meier method and Cox regression. Also, we performed multivariate analysis of the separate factors of the model and other probable risk factors. Results We collected baseline and 30 day follow-up data in 3996 patients of which 357 with HBR (9%). Access site bleedings occurred in 3% of patients with HBR vs 2% without (sens. 0.13; spec. 0.98). Patients with HBR showed 5% non-access site bleedings versus 1% in non HBR (sens. 0.21; spec. 0.99). Survival curves and hazard ratios presented in figure 1 show that these differences are significant only for non-access site bleedings (HR: 4.2, 95% CI: 2.47-7.30). The multivariate analysis is presented in table 1. All bleeding events were predicted by age ≥ 60 and peripheral arterial disease. Furthermore, non-access site bleedings were predicted by anaemia and bleeding events in the previous year. Additional risk factors for access site bleedings were female sex and double access site punction. Conclusion The simplified risk model showed to be conservative in the determination of HBR as depicted by the sensitivity and specificity. However, it showed good discriminative value for non-access site bleedings which was driven by anemia and a history of bleedings. Furthermore, these results suggest that age ≥60 and peripheral arterial disease should be taken into consideration. Extra precaution for access site bleedings should also be taken in female patients and in the case of double access site punction.Figure 1Table 1

Parsimonious versus extensive score: can we simplify bleeding risk stratification after percutaneous coronary intervention without losing specificity?

Abstract Background/Introduction Prediction of bleeding risk in patients receiving dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has been repeatedly attempted and resulted in multiple risk models. To promote the adoption and use of risk stratification among clinicians, a consortium in the South East of the Netherlands, the "ZON-HR", has created a simple binary variant of the existing logistic models. This model includes commonly available factors which can be incorporated into the PCI report to generate stratification. In this "parsimonious" model, high bleeding risk (HBR) is stratified according to: history of intracranial haemorrhage, previous spontaneous bleeding, Hb &amp;lt; 11 g/dL, eGFR&amp;lt; 30. Purpose We aimed to perform an external validation of our model for bleeding risk and to demonstrate its discriminative value in comparison with the PRECISE DAPT score, an acknowledged risk score. Methods We performed a post hoc analysis of the GLOBAL LEADERS trial, a multicenter randomized trial, comparing ticagrelor monotherapy after one month of DAPT with standard DAPT after PCI. We stratified the patients for HBR according to the ZON-HR or a PRECISE-DAPT score ≥ 25. Bleeding events one year after PCI were compared in the entire population and in subgroups for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), Ticagrelor monotherapy and DAPT. Results Of the 15968 patients included in GLOBAL LEADERS, 1059 patients were excluded due to missing variables required for either model. Among the 14909 patients, 17% had HBR according to the PRECISE DAPT score, 4% according to ZON-HR and 3% according to both. Bleeding events occurred in 8.5% and 13% of HBR defined by PRECISE DAPT or ZON-HR respectively. Patients with HBR according to both models showed 13% bleedings as opposed to 5% in non-HBR. Table 1 presents the sensitivity and specificity. Regression analysis (figure 1) demonstrated that patients with HBR according to either model have significantly more bleedings. This was also significant in all subgroups except for ACS patients receiving standard DAPT when the ZON-HR model was used. Conclusion The ZON-HR model is more conservative compared to the PRECISE DAPT score as depicted by the sensitivity and specificity. This can be explained by the larger number of risk factors used in the PRECISE DAPT score that cumulatively contributes to the sensitivity as opposed to the binary ZON-HR model which is more specific. However, the survival curves and hazard ratios showed good predictive value of both models for bleeding risk in the overall population.Table 1.Figure 1.

Physicians' perspectives on percutaneous left atrial appendage occlusion for patients with atrial fibrillation

There has been an increasing uptake of transcatheter left atrial appendage occlusion (LAAO) for stroke reduction in atrial fibrillation. To investigate the perceptions and approaches among a nationally representative sample of physicians. Using the American Medical Association Physician Masterfile, we selected a random sample of 500 physicians from each of the specialties: general cardiologists, interventional cardiologists, electrophysiologists, and vascular neurologists. The participants received the survey by mail up to three times from November 9, 2021 to January 14, 2022. In addition to the questions about experiences, perceptions, and approaches, physicians were randomly assigned to 1 of the 4 versions of a patient vignette: white man, white woman, black man, and black woman, to investigate potential bias in decision-making. The top three reasons for considering LAAO were: a history of intracranial bleeding (94.3%), a history of major extracranial bleeding (91.8%), and gastrointestinal lesions (59.0%), whereas the top three reasons for withholding LAAO were: other indications for long-term oral anticoagulation (87.7%), a low bleeding risk (77.0%), and a low stroke risk (65.6%). For the reasons limiting recommendations for LAAO, 59.8% mentioned procedural risks, 42.6% mentioned "limiting efficacy data comparing LAAO to NOAC" and 32.8% mentioned "limited safety data comparing LAAO to NOAC." There was no difference in physicians' decision-making by patients' race, gender, or the concordance between patients' and physicians' race or gender. In the first U.S. national physician survey of LAAO, individual physicians' perspectives varied greatly, which provided information that will help customize future educational activities for different audiences. Although diverse practice patterns of LAAO have been documented, little is known about the reasoning or perceptions that drive these variations. Unlike prior surveys that were directed to Centers that performed LAAO, the current survey obtained insights from individual physicians, not only those who perform the procedures (interventional cardiologists and electrophysiologists) but also those who are closely involved in the decision-making and referral process (general cardiologists and vascular neurologists). The findings identify key evidence gaps and help prioritize future studies to establish a consistent and evidence-based best practice for AF stroke prevention.

Intracranial bleeding and associated outcomes in atrial fibrillation patients undergoing percutaneous left atrial appendage occlusion: Insights from National Inpatient Sample 2016-2020.

Percutaneous left atrial appendage occlusion (LAAO) has proved to be a safer alternative for long-term anticoagulation; however, patients with a history of intracranial bleeding were excluded from large randomized clinical trials. The purpose of this study was to determine outcomes in atrial fibrillation (AF) patients with a history of intracranial bleeding undergoing percutaneous LAAO. National Inpatient Sample and International Classification of Diseases, Tenth Revision, codes were used to identify patients with AF who underwent LAAO during the years 2016-2020. Patients were stratified based on a history of intracranial bleeding vs not. The outcomes assessed in our study included complications, in-hospital mortality, and resource utilization. A total of 89,300 LAAO device implantations were studied. Approximately 565 implantations (0.6%) occurred in patients with a history of intracranial bleed. History of intracranial bleeding was associated with a higher prevalence of overall complications and in-patient mortality in crude analysis. In the multivariate model adjusted for potential confounders, intracranial bleeding was found to be independently associated with in-patient mortality (adjusted odds ratio [aOR] 4.27; 95% confidence interval [CI] 1.68-10.82); overall complications (aOR 1.74; 95% CI 1.36-2.24); prolonged length of stay (aOR 2.38; 95% CI 1.95-2.92); and increased cost of hospitalization (aOR 1.28; 95% CI 1.08-1.52) after percutaneous LAAO device implantation. A history of intracranial bleeding was associated with adverse outcomes after percutaneous LAAO. These data, if proven in a large randomized study, can have important clinical consequences in terms of patient selection for LAAO devices.

Efficacy and safety of anticoagulation in atrial fibrillation patients with intracranial hemorrhage: A systematic review and meta-analysis.

Background: The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a history of intracranial hemorrhage (ICH) remain controversial. We performed a systematic review and meta-analysis to compare the safety and efficacy of starting oral anticoagulation (OAC) and non-oral anticoagulation in these patients. Methods: PubMed, Cochrane Library, and Embase were searched from inception to 01 May 2022 for randomized controlled trials and cohort studies, reporting effectiveness and safety outcomes for anticoagulation therapy in atrial fibrillation patients with intracranial hemorrhage. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration tool were used to evaluate bias risks for all randomized controlled trials (RCTs) and cohort studies. An effects model was applied to calculate adjusted hazard ratios (aHRs) for randomized controlled trials and cohort studies. Results: We analyzed data from two randomized controlled trials (304 patients) and seven Cohort studies (17,477 patients). Compared to non-oral anticoagulation, starting oral anticoagulation therapy reduced the risk of Ischemic Stroke/Systemic Embolism (SE) (aHR: 0.64, 95% CI: 0.55-0.57) and all-cause death (aHR: 0.53, 95% CI: 0.35-0.80) in atrial fibrillation patients and a prior history intracranial hemorrhage. Starting oral anticoagulation therapy did not increase the risk of recurrent intracranial hemorrhage (aHR: 1.07, 95% CI: 0.66-1.74), but increased the risk of major bleeding (aHR: 1.38, 95% CI: 1.00-1.91) than no oral anticoagulation therapy. The DOACs had a lower risk of Ischemic Stroke/SE (aHR: 0.84, 95% CI: 0.70-1.00), recurrent intracranial hemorrhage (aHR: 0.63, 95% CI: 0.49-0.82), and all-cause death (aHR: 0.65, 95% CI: 0.48-0.88) compared to warfarin. According to subgroup analyses, starting oral anticoagulation therapy have a higher risk of recurrent intracranial hemorrhage than non-oral anticoagulation therapy (aHR: 1.57, 95% CI: 1.36-1.81) for Asians. Conclusion: After intracranial hemorrhage in atrial fibrillation patients, restarting or initiating oral anticoagulation therapy decreased the risk of Ischemic Stroke/SE and all-cause death but did not increase the risk for recurrent intracranial hemorrhage. Direct oral anticoagulations have better efficacy and safety than warfarin if oral anticoagulation therapy is started. However, starting oral anticoagulation increases the risk for recurrent intracranial hemorrhage in the Asian region.

Abstract WP18: Association Of Quality Of Life Domains And Clinical Symptoms In Familial Cerebral Cavernous Malformation Patients

Background: Familial cerebral cavernous malformation (FCCM) is characterized by multiple brain lesions at risk for intracranial hemorrhage (ICH) and neurological morbidity, affecting quality of life (QoL). PROMIS-29 is a QoL survey validated in some neurological diseases but has not yet been evaluated for FCCM. We aimed to assess whether PROMIS-29 health domains are associated with clinical symptoms in FCCM patients. Methods: PROMIS-29 surveys assessing seven QoL domains were completed by 198 FCCM patients &gt;=18 years either at a baseline or follow-up visit in the Brain Vascular Malformation Consortium CCM study. Raw PROMIS-29 domain scores were converted to T scores that are standardized to a reference population with mean 50 and SD 10, and oriented so that higher scores are unfavorable. One-sample t-tests and p-values assessed whether mean T-scores were significantly different from 50 (p&lt;0.05). Multivariable linear regression was used to test whether domain scores were associated with history of ICH, seizures, or headaches at time of survey, adjusting for age and sex. Results: Compared to a reference population, FCCM patients had significantly higher anxiety (52.7, 95% CI: 51.3-54.2, p&lt;0.001), pain (52.5, 95% CI: 51.0-54.0, p=0.002), and physical functioning scores (52.0, 95% CI: 51.4-54.5, p&lt;0.001), but lower social participation scores (46.9, 95% CI: 45.4-48.5, p&lt;0.001). History of ICH and headaches were significantly associated with 4 domains each (all &gt;3 points, p&lt;0.05, Table), while seizures were not associated. Fatigue was the only affected domain in common. Conclusion: FCCM patients differed significantly from the reference population on anxiety, pain, physical functioning, and social participation domains. These same domains were significantly associated with history of ICH or headaches in patients. Further studies will determine whether changes in health domains are associated with changes in clinical symptoms.

Management of a patient with factor X deficiency with FEIBA: a case report

Abstract Hereditary factor X (FX) deficiency is a rare autosomal recessive disorder that increases bleeding tendencies, ranging from epistaxis to intracranial haemorrhage (ICH), which can be life-threatening. Single factor concentrates are recommended for treating rare bleeding disorders; however, in India most people with FX deficiency are treated with fresh frozen plasma (FFP). We report a case of FX deficiency in a child with a history of intracranial bleeding who was found to have a novel mutation in the F10 gene. Although managed with weekly prophylactic FFP infusions, he continued to experience regular bleeding including two further instances of ICH. Other therapeutic options were unavailable or unaffordable. When the Indian Government added FEIBA to the essential drug list, a decision was made to try FEIBA prophylaxis to better manage his bleeding. In 2019, he was started on a weekly dose of FEIBA, 500 IU (20 IU/ kg and his prophylactic FFP transfusion regimen was stopped. His bleeding episodes started to reduce after two months of starting FEIBA prophylaxis. Over the last three years he has had only four minor bleeding episodes and has remained completely free of major bleeding. He is now able to receive home-based therapy and his prognosis can be considered to be improved. FEIBA may be a useful medicinal therapy for FX-deficient patients who suffer severe haemorrhagic episodes in countries where plasma-derived factor X (pdFX) is not available.

Prehospital misdiagnosis of acute cerebral disease for acute coronary syndrome: a retrospective study

ObjectiveIn cerebrovascular accidents symptoms, laboratory results and electrocardiogram (ECG) changes can mimic acute coronary syndrome (ACS) and is subsumed as neurogenic stunned myocardium. So far, data regarding the frequency of cerebrovascular accidents misdiagnosed for ACS in a prehospital setting are missing. This study aims to quantify misdiagnoses and discover discriminating features.MethodsIn a retrospective cohort study, prehospital and hospital medical records of all patients treated by physician-staffed emergency medical teams in the city of Bonn (Germany) with suspected ACS in 2018 were evaluated regarding medical history, prehospital symptoms and findings as well as hospital diagnoses.ResultsFrom 758 patients admitted for presumed ACS, 9 patients (1.2%, 95% CI: 0.5–2.2%) suffered from acute cerebral disease (ACD group). Mainly, diagnoses were cerebrovascular accidents and one case of neuroborreliosis. A history of intracranial haemorrhage was found more often in the ACD group compared to the remaining cohort (OR 19, p = 0.01), while a history of arterial hypertension was less frequent (OR 0.22, p = 0.03). Presentation with headaches (OR 10.1, p = 0.03) or neurological symptoms (OR 16.9, p = 0.01) occurred more frequent in the ACD group. ECG changes were similar between groups.ConclusionAcute cerebral disease misdiagnosed for ACS seems more common than assumed. Out of 758 patients with presumed ACS, 9 patients (1.2%) suffered from ACD, which were cerebrovascular accidents mainly. This is highly relevant, since prehospital treatment with heparin and acetylsalicylic acid is indicated in ACS but contraindicated in cerebrovascular accidents without further diagnostics. Thus, discriminating these patients is crucial. An attentive patient history and examination may be the key to differentiating ACD. Due to small ACD group size, further studies are needed.

The characteristics and long-term outcomes of acute promyelocytic leukemia patients with early intracranial hemorrhage.

Intracranial hemorrhage (ICH) is a major cause of early death (ED) and leads to poor prognosis in acute promyelocytic leukemia (APL). We retrospectively described 27 unselected APL patients who experienced early ICH. The ED rate was 37%. The 3-year overall survival (OS) rate was 45.4%, while the 3-year OS rate of patients who survived through induction therapy was 87.5%. No patient experienced central nervous system leukemia (CNSL). Concurrent differentiation syndrome, white blood cell count, prothrombin time and D-dimer were related to death. Although the ED rate among APL patients with early ICH was high, patients with early ICH had a favorable outcome after surviving through induction therapy. CNSL was rare despite a history of ICH during induction therapy. Compared with APL patients without ICH, it seems unnecessary to administer additional measures to prevent CNSL for this subpopulation in the era of all-trans retinoic acid and arsenic trioxide, but this needs further validation in prospective trials.

Effect of Statin Therapy on Mortality and Recurrence of Intracerebral Hemorrhage in Patients With Spontaneous Intracerebral Hemorrhage.

Statins can play an essential role in the tertiary and primary prevention of cardiovascular events by reduction of cholesterol in a stroke patient. This meta-analysis aims to assess statin therapy's effect on mortality and recurrence of Intracranial Hemorrhage (ICH) in patients with spontaneous ICH. The current meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was performed using PubMed, EMBASE, and Cochrane Library to identify studies assessing the use of statins in patients with ICH. The primary outcome assessed in the current meta-analysis was a hemorrhagic stroke. The secondary outcomes included cardiac-related events and all-cause mortality. A total of 9 studies were included in the current meta-analysis enrolling 49027 patients, with 8094 patients on statin therapy and 40933 patients in the control group. The risk of recurrent ICH was significantly lower in patients receiving stains (RR: 0.81, 95% CI: 0.67-0.99, p-value: 0.02) compared to placebo. However, no significant differences were observed regarding all-cause mortality (RR: 0.80, 95% CI: 0.53-1.20, p-value: 0.27) and cardiovascular events (RR: 1.24, 95% CI: 0.88-1.74). In ICH patients, statins can reduce the risk of recurrent ICH in patients with a history of ICH. However, statins had no significant effect on all-cause mortality and cardiovascular events.

Swallowing-related quality of life in children with oesophageal atresia: a national cohort study

Swallowing and feeding disorders are a major concern for children with oesophageal atresia (OA) after primary or staged OA repair. Primary OA repair is associated with higher rates of short-term complications in preterm infants with very low birth weight (VLBW) or extreme low birth weight (ELBW). On the other hand, primary repair may have the benefit of early commencement of oral feedings. We hypothesize that also in the medium-term, swallowing-related quality of life is better after primary oesophageal repair. We conducted a prospective cross-sectional study on swallowing quality in a national cohort of former VLBW and ELBW children with OA, using the structured paediatric swallowing quality of life (pedSWAL-QOL) questionnaire. Results were correlated with surgical approach and baseline clinical data. Principal component analysis of pedSWAL-QOL domains was performed. In total, 44 complete data sets of 78 children were available. The mean age of children was 8.5 years (SD = 7.4), and 23 children (52%) had primary OA repair. The overall median pedSWAL-QOL score was 2 (IQR = 0–3), representing a high swallowing-related quality of life, independent of surgical technique (p = 0.086). Children with a history of intracranial haemorrhage (ICH) (p = 0.002) and those with VACTERL association (p = 0.008) had significantly decreased enjoyment with eating. In addition, children with VACTERL association had problems to find suitable foods (p = 0.04). Conclusion: In this national cohort of VLBW and ELBW preterm-born children with OA, swallowing-related quality of life is good, mostly independent of initial surgery. Children with OA and ICH or VACTERL association may require more intense support with feeding.What is Known:• Dysphagia, resembling feeding and swallowing disorders, is common in children and adults with repaired oesophageal atresia. Nevertheless, dysphagia in children with oesophageal atresia decreases with age.• Parents of younger children suffer from increased anxiety and fear regarding eating and swallowing abilities of their children.What is New:• Swallowing-related quality of life in former preterm children with oesophageal atresia is good, independent of initial surgical approach (primary vs. staged repair), even in very low birth weight or extreme low birth weight infants. • Children suffering from VACTERL association or intracranial haemorrhage show decreased enjoyment with eating.

Effect of oral anticoagulation therapy in atrial fibrillation patients with a history of intracranial hemorrhage: a systematic review and meta-analysis.

Use of oral anticoagulants (OACs) among atrial fibrillation (AF) patients surviving intracranial hemorrhage (ICH) represents a challenge due to the difficult balance between thrombosis and hemorrhage. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of OACs resumption in AF patients with a history of ICH during long-term follow-up. The outcome measures were ischemic stroke (IS), IS or systemic embolism (SE), all-cause death, recurrent ICH and major bleeding. Meta-analyses of pooled odds ratios (ORs) were conducted with random-effects models. A total of 2 randomized controlled trials (RCTs) and 9 observational studies were included, covering 18,115 patients with AF and a history of ICH. The risk of IS was not statistically different between the group of patients receiving OAC therapy and the no-OAC group (OR: 0.41, 95% CI: 0.16 to 1.0, P=0.05). The rate of IS or SE (OR: 0.42, 95% CI: 0.27 to 0.70, P=0.0008), all-cause death (OR: 0.54, 95% CI: 0.41 to 0.70, I2=42%, P<0.00001) were significantly decreased in patients receiving OAC therapy compared to those with no-OAC therapy. The pooled OR estimates for ICH recurrence (OR: 1.46, 95% CI: 0.94 to 2.26, P=0.09) and major bleeding (OR: 1.35, 95% CI: 0.86 to 2.11, P=0.19) were not significantly increased in the OAC therapy group. There was heterogeneity between the results of observational studies and RCTs in terms of all-cause death (I2=83.4%). Considering the heterogeneity in results between observational studies and RCTs, as well as the limited number and small size of RCTs, high grade evidences are needed. Pooled analysis is required when more RCTs are completed in the future to resolve this therapeutic dilemma.