Epistaxis Severity Research Articles

Comparison of traditional and next-generation oral anticoagulants in the etiology of epistaxis

Background/Aim: There is a dearth of studies addressing the effects of next-generation anticoagulants on epistaxis. The aim of this investigation was to determine whether there are any differences between traditional and next-generation anticoagulants in the etiology of epistaxis. Methods: This retrospective cohort study focused on a total of 7,110 individuals (3,278 females (46.1%) and 3,832 males (53.9%)) diagnosed with epistaxis between 2018 and 2022; the mean age of the patients was 37.7 years. Patient data (age, gender, outpatient and inpatient treatments, relevant laboratory parameters, and treatment evidence) were retrospectively reviewed from a hospital database. The severity of epistaxis was assessed based on treatment notes. Patients with hypertension and those undergoing antiaggregant therapy were excluded from the study. International Classification of Diseases (ICD) codes from the automated system were examined retrospectively. The data were used to establish three patient groups: the first group consisted of individuals taking next-generation oral anticoagulants, the second group consisted of individuals taking traditional oral anticoagulants, and the third group consisted of healthy controls. Results: We found statistically significant differences among the groups in terms of age, the severity of epistaxis, the treatment modality, and laboratory findings (P<0.001); no statistically significant difference was found in terms of gender (P=0.954). Group 2 contained the largest number of hospitalized patients and patients with severe active nosebleeds. Conclusion: Next-generation anticoagulants are more reliable than traditional anticoagulants in terms of the severity of epistaxis, the need for hospitalization, and laboratory results.

Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia

BackgroundHereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life.MethodsWe conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations).ResultsThe trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was −0.94 points (95% confidence interval [CI], −1.57 to −0.31; P=0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was −1.4 points (95% CI, −2.6 to −0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash.ConclusionsAmong patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).

Molecular and Functional Cargo of Plasma-Derived Exosomes in Patients with Hereditary Hemorrhagic Telangiectasia.

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder leading to frequent bleeding in several organs. As HHT diagnosis is demanding and depends on clinical criteria, liquid biopsy would be beneficial. Exosomes from biofluids are nano-sized vesicles for intercellular communication. Their cargo and characteristics represent biomarkers for many diseases. Here, exosomes of HHT patients were examined regarding their biosignature. Methods: Exosomes were isolated from the plasma of 20 HHT patients and 17 healthy donors (HDs). The total exosomal protein was quantified, and specific proteins were analyzed using Western blot and antibody arrays. Human umbilical vein endothelial cells (HUVECs) co-incubated with exosomes were functionally examined via immunofluorescence, proliferation, and scratch assay. Results: The levels of the angiogenesis-regulating protein Thrombospondin-1 were significantly higher in HHT compared to HD exosomes. Among HHT, but not HD exosomes, a negative correlation between total exosomal protein and soluble Endoglin (sENG) levels was found. Other exosomal proteins (ALK1, ALK5) and the particle concentration significantly correlated with disease severity parameters (total consultations/interventions, epistaxis severity score) in HHT patients. Functionally, HUVECs were able to internalize both HD and HHT exosomes, inducing a similar change in the F-Actin structure and a reduction in migration and proliferation. Conclusions: This study provided first insights into the protein cargo and function of HHT-derived exosomes. The data indicate changes in sENG secretion via exosomes and reveal exosomal Thrombospondin-1 as a potential biomarker for HHT. Several exosomal characteristics were pointed out as potential liquid biomarkers for disease severity, revealing a possible new way of diagnosis and prognosis of HHT.

The Role of Thalidomide and Its Analogs in the Treatment of Hereditary Hemorrhagic Telangiectasia: A Systematic Review.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations and telangiectases, in which the endothelium and immune system play a role in the pathophysiology. Therefore, treatments with antiangiogenic properties which are also regarded as immunomodulators were demonstrated to play an important role in treatment. This systematic review aimed to gather the accumulated information of the use of thalidomide and its analogs in the treatment of HHT. Methods: In this systematic review, publications that were published up to March 2024 and met the inclusion criteria were compiled using the keywords 'thalidomide', 'lenalidomide', 'pomalidomide', 'immunomodulatory drugs' and 'HHT' in Medline and Scholars databases. Results: A total of 53 articles were evaluated and 15 were included in the study. Thalidomide was the predominant used agent and was observed to be used in patients with ages ranging from 37 to 77 years, with doses ranging from 50 to 200 mg daily, and the mean follow-up period was observed to be 6-60 months. Assessments regarding efficacy were based on the epistaxis severity score (ESS), hemoglobin level, and transfusion independence. While thalidomide showed significant efficacy, it also had an adverse event rate of any severity of up to 85% of patients. Use of lenalidomide to control bleeding in HHT was reported in a single case report, while the use of pomalidomide was observed to be investigated in Phase 1 and Phase 2 studies in patients aged 48 to 70 years, with doses ranging from 1 to 5 mg daily for 6-24 months. This treatment was reported to provide significant improvement in hemoglobin levels and ESS. Adverse events of any severity were observed at a frequency of 60-66%. Conclusions: Antiangiogenic agents such as thalidomide, lenalidomide, and pomalidomide may be effective in managing HHT. However, further studies are needed to optimize the timing, dose, and sequence.

EFFECT OF BEVEL DIRECTION OF THE ENDOTRACHEAL TUBE ON THE PROPORTION OF CASES DEVELOPING EPISTAXIS DURING NASOTRACHEAL INTUBATION-A RANDOMIZED CONTROLLED INTERVENTIONAL STUDY

Objective: Nasotracheal intubation is associated with a number of complications, most commonly nasal trauma or epistaxis. The aim of the study is to determine the effect of conventional versus cephalad direction of the bevel of endotracheal tube on the development of epistaxis during nasotracheal intubation. Methods: A total of 74 adults aged 18 to 50 y posted for surgeries requiring nasotracheal intubation were randomly divided into group A (Conventional) and group B (Interventional). After induction of anesthesia, in group a bevel direction of thermo softened PVC endotracheal tube was towards the nasal septum in the nasal passage and cephalad in group B, later nasotracheal intubation was completed with direct laryngoscopy and Magill forceps. After five minutes direct laryngoscopy was done to check for presence of epistaxis and its severity. Degree of resistance, nasal passage time, intubation time and haemodynamic parameters (heart rate, blood pressures) were also assessed and compared. Results: The incidence of epistaxis was significantly lower in group B (Interventional) than group A (Conventional) [15 vs 27; p-value = 0.005], severity of epistaxis [0/1/2] were also significantly lower in group B [22/12/3] than group A [10/15/12] [p value = 0.001]. There was significant difference in haemodynamic parameters between both groups at 1 min till 7 min post intubation. There was no significant difference in degree of resistance, nasal passage time and mean intubation time. Conclusion: The cephalad direction of the bevel of endotracheal tube in nasal passage during nasotracheal intubation decreases the chances of developing epistaxis and its severity. Hemodynamic parameters are also more stable in cephalad direction.

Risk factors of epistaxis in rural Denmark: a cross-sectional population-based survey of data from the Lolland-Falster health study.

Epistaxis is a common condition that affects about 60% of the population in their lifetime, with 6% needing medical attention. Little is known about the epidemiology and risk factors of epistaxis outside the health care system. This study aimed to investigate the prevalence and risk factors of epistaxis in a rural Danish population using data from the Lolland-Falster Health Study (LOFUS). We conducted a cross-sectional survey based on data from LOFUS, a household-based, prospective cohort study in the rural provincial area of Lolland-Falster, Denmark. We enrolled 10,065 participants (≥ 50 years) and collected data on demographics, comorbidities, medication, lifestyle factors, and laboratory parameters. Logistic regressions were used to test for correlations between epistaxis and different risk factors. In total 5.3% of the participants had experienced epistaxis within the past 30 days, and 7.9% had sought medical attention for epistaxis at some point in their lives. We identified several factors that were significantly correlated with increased odds of epistaxis, such as male gender, age group 50-59 years, high BMI (> 25), allergy, diabetes, hypertension, atherosclerosis, angina, and anticoagulant treatment. Excellent or good self-reported health was correlated to significantly lower odds of epistaxis. This study provides a comprehensive overview of the prevalence and risk factors of epistaxis outside the health care system. Our study suggests that preventive measures targeting these risk factors may reduce the incidence and severity of epistaxis in this population.

Změna v preskripci antikoagulační terapie ve vztahu k závažné epistaxi

Summary Introduction: Epistaxis is vascular bleeding in the area of the nasal mucosa. Anticoagulation therapy increases the incidence of epistaxis. Anticoagulants are divided into direct and indirect depending on their effects. Direct anticoagulants are primarily novel oral anticoagulants (NOACs). Warfarin belongs to the group of indirect anticoagulants. Methodology: The retrospective study evaluates the benefit of the introduction of NOACs for otorhinolaryngology in connection with the occurrence of severe epistaxis. A comparison was done of the number of hospitalized adult patients with epistaxis over the course of 6 years during warfarin and NOAC treatment who were hospitalized with epistaxis at the ENT department of KNTB in Zlín between 2017–2022. The patient’s age and gender were also monitored. The severity of epistaxis was evaluated in relation to the used nasal packing and general anesthesia. The relationship with SÚKL data on the number of issued anticoagulant drugs is described. Results: During 6 years, a total of 221 patients were hospitalized for epistaxis, 32 were taking warfarin, and 20 were taking NOACs. The average age of patients with anticoagulant treatment was 78 years, represented by 61.5% men and 38.5% women. Over the years, we see a decrease in the number of epistaxis cases in warfarin patients; with NOACs the number is stationary. According to SÚKL statistics on preparations delivered to pharmacies in 2017 and 2022, there was a decrease in the prescription of warfarin by 44%; on the contrary, an increase of NOAC was up to 170%. Conclusion: With the decrease in the prescription of warfarin, we observe a reduced number of hospitalizations with severe epistaxis with this type of treatment. On the contrary, the increase in anticoagulation therapy with preparations from the NOAC group does not lead to an increase in the incidence of epistaxis, which also benefits the ENT field. Key words epistaxis – anticoagulants – NOAC – warfarin

Surgery or No Surgery? Exploring the Dilemma of Epistaxis Management in Patients with HHT.

Background: Epistaxis, particularly in Hereditary Hemorrhagic Telangiectasia (HHT) patients, is a common otolaryngological emergency, often requiring complex management. A hierarchy of increasingly invasive interventions, from external compression of the nasal pyramid to nostril closure, is typically proposed and applied. Methods: We conducted a retrospective study on HHT patients to assess the effectiveness and longevity of invasive procedures postoperatively. Data were collected using the Epistaxis Severity Score (ESS) questionnaire. The primary focus was on changes in the frequency and intensity of epistaxis, while the secondary focus was on the overall quality of life. Results: This study found that invasive procedures initially improved the frequency and intensity of epistaxis in HHT patients. However, within 1 to 9 months postoperatively, these benefits often diminished, with hemorrhagic symptoms recurring at similar or worsened levels. Conclusions: The findings suggest a need for a cautious and restrained approach to using invasive treatments in managing epistaxis in HHT patients. Highly invasive procedures should be reserved for cases where less invasive methods fail, due to their temporary effectiveness and the risk of causing anatomical-functional changes in the rhino-sinus area, complicating future management of severe epistaxis.

Incidence of Neoplasm in Patients Referred for Epistaxis.

Objectives: The primary objective was to identify the incidence of neoplastic disease in patients referred for epistaxis. Secondary objectives included identification of any mass lesion, and the need for further workup with imaging and/or biopsy as well as risk factors associated with identification of a mass lesion. Study Design: Retrospective cohort study. Methods: Medical records of adult patients who presented to Tufts Medical Center over an 11 year period (2010-2021) with a chief complaint of epistaxis were reviewed. The primary outcome was identification of a nasal or nasopharyngeal mass. Patient characteristics including age, sex, race, smoking status, anticoagulation, comorbidities (hypertension, allergic rhinitis, vasculitis), and treatment of epistaxis (used as surrogate for severity of epistaxis) were also examined. Results: A total of 1164 patients met inclusion and exclusion criteria. Thirty-six nasal masses were found among patients presenting with epistaxis (3.09%, P < .001), comprised primarily of benign etiology (2.66%) including nasal polyposis and thornwaldt cyst. Asian race correlated with finding of mass lesion (75%, P = .007). Five malignancies were found (0.43%) including nasopharyngeal carcinoma (2 patients), extranodal natural killer T-cell lymphoma (2 patients), and nasal adenocarcinoma (1 patient). Conclusions: Epistaxis is a common cause for referral to otolaryngology. Although the incidence of neoplasm in our patient population was low, nasal mass lesions warranting further workup were identified in 36 patients. Findings of neoplasm were more common in patients of Asian ethnicity, which may reflect the increased prevalence of nasopharyngeal carcinoma in this population. Otolaryngologic evaluation and nasal endoscopy should be considered in all cases of epistaxis.

Impact of COVID-19 lockdown on hospital admissions for epistaxis in Germany.

Reports of a decrease in hospital admissions during the coronavirus disease 2019 (COVID-19) lockdown period have raised concerns about delayed or missed diagnoses and treatments for non-COVID-19-related illnesses. To investigate the impact of the COVID-19 pandemic-induced lockdown and its end on hospital admissions of patients with epistaxis in Germany. A retrospective analysis based on the national database of the Hospital Remuneration System was used to compare hospital admissions during defined time periods between 2019 and 2022 with the lockdown period as the reference period. This was done on a weekly basis before, during, and after the lockdown. An Interrupted Time Series was used as the analysis method. In our analysis, we included 26183 patients. The implementation of the lockdown led to a substantial reduction in the overall occurrence of epistaxis among patients (P < 0.05). This effect was most pronounced in the age group of 0-39 years, where the decrease was highly significant (P < 0.001). However, there was no change observed in patients aged 80 years and older (not significant). With the end of the lockdown period, the overall number of patients, especially in the youngest age group, increased abruptly and significantly (P < 0.01). During the lockdown period, there was a decrease in hospital admissions for younger patients with epistaxis, possibly due to the fear of COVID-19 exposure. We also conclude that the severity of epistaxis was not underestimated in the elderly during the pandemic.

Tacrolimus as a Promising Drug for Epistaxis and Gastrointestinal Bleeding in HHT

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting the patient’s quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and the need for blood transfusions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT. Methods: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5–2 mg/day) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. The epistaxis severity score (ESS) and hemoglobin levels were the parameters used to evaluate the impact of tacrolimus. The occurrence of side effects was also recorded. Results: Tacrolimus was well tolerated in all of the patients except 2 (who stopped the treatment). The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced when comparing the ESS before and after the treatment. Hemoglobin levels significantly increased, overcoming the anemia, during the course of the treatment. Conclusion: Tacrolimus at low doses should be considered as a promising treatment for epistaxis and gastrointestinal bleeding in HHT.

PATH-HHT, a Double-Blind, Randomized, Placebo-Controlled Trial in Hereditary Hemorrhagic Telangiectasia Demonstrates That Pomalidomide Reduces Epistaxis and Improves Quality of Life

Introduction Hereditary hemorrhagic telangiectasia (HHT), the second most common bleeding disorder worldwide, affects 1 in 5000 people and is characterized by extensive formation of telangiectasia and arteriovenous malformations (AVM) in mucosa, lung, brain, and liver. The primary clinical manifestation is recurrent, often severe epistaxis which commonly results in iron deficiency anemia, emergency room visits, hospitalizations, and reduced quality of life (QOL). Though non-randomized and/or underpowered studies have suggested that systemic bevacizumab or thalidomide may be effective in treating HHT, there have been no pivotal studies and therefore no FDA or EMA approved therapies. Methods PATH-HHT was an NHLBI-funded, randomized, placebo-controlled clinical trial conducted at 13 centers in the US to determine the safety and efficacy of pomalidomide for bleeding in HHT. Pomalidomide was supplied by Celgene and Bristol Myers Squibb. Patients were randomized in a 2:1 ratio to receive pomalidomide 4 mg daily or matching placebo for 6 months. Dose reductions were allowed for toxicity. The primary endpoint was the change in the Epistaxis Severity Score (ESS), a well-validated bleeding score in HHT, from baseline (randomization) to the end of the six-month treatment period, analyzed using a mixed model for repeated measures with adjustment for baseline value, center, treatment, visit, and treatment by visit interaction. Key secondary endpoints included 1) change in the average daily self-reported epistaxis duration from the four weeks preceding the baseline visit to weeks 20-24 of treatment, 2) amount of parenteral iron infused or blood transfused, and 3) change in QOL measurements, including an HHT-specific QOL score. Results PATH-HHT opened in November 2019 and was closed to enrollment by the NHLBI in June 2023 after a planned 75% interim analysis met a prespecified threshold for efficacy. A total of 144 patients were randomized and treated (95 pomalidomide, 49 placebo). Early study discontinuation was 25% in pomalidomide: 14% AE, 11% withdrawn, 1 unrelated death, compared with placebo (4% withdrawn). Across groups, 8% were terminated after 12 weeks for early study closure. Participants included 48% females, 11% non-white race; mean (± SD) age was 58.8±12.2 years. The mean ESS at baseline was 5.0±1.5 (4.9 pomalidomide, 5.2 placebo), consistent with moderate to severe epistaxis. At 24 weeks, the ESS in patients treated with pomalidomide decreased by a mean [95% CI] of -1.84 [-2.24, -1.44] and in the placebo group decreased by -0.89 [-1.39, -0.39] (mean difference -0.95 [-1.58, -0.32], p = 0.003) (Figure, Panel A). Difference between groups was apparent by 12 weeks (mean difference -0.52, 95% CI [-1.04, -0.01], p = 0.045). The HHT-specific QOL score, which ranges from 0 to 16 with higher scores indicating more limitations, also decreased more in the pomalidomide (mean -2.6, 95% CI [-3.3, -1.9]) vs the placebo group at 24 weeks (mean -1.2, 95% CI [-2.1, -0.3], p = 0.015) (Figure, Panel B). Adverse events that occurred more in the pomalidomide group included mild to moderate neutropenia (45% vs. 10%), constipation/diarrhea (60% vs. 37%), and rash (36% vs. 10%). Venous thrombosis occurred in 2% of patients in each group. Conclusion PATH-HHT is the largest and the first adequately powered, randomized trial of systemic therapy in HHT. The study demonstrated a significant and highly clinically relevant reduction in epistaxis in pomalidomide-treated patients as well as an improvement in the HHT-specific QOL score. Pomalidomide may offer a novel approach to management of HHT. Since plasma was collected from patients in this study before and at the end of treatment, additional studies may identify biomarkers predicting pomalidomide responses.

The bleeding diathesis in patients with hereditary haemorrhagic telangiectasia is not due to impaired platelet function

BackgroundPatients with the rare disease; Hereditary haemorrhagic telangiectasia (HHT) often bleed from telangiectatic lesions in mucosal surfaces. Studies suggest that impaired platelet function may also play a role in their bleeding tendency. The aim of the present study was to investigate whether HHT-patients with epistaxis have impaired platelet function.MethodWe conducted a case–control study based on a sample size calculation and included 22 HHT-patients (inclusion criteria: epistaxis severity score ≥ 4, no intake of medicine affecting platelet function the last 5 days, HHT-type 1 or 2, age ≥ 18 years) and 20 controls. We assessed the platelet function with standard haemostasis parameters, flow cytometry (platelet function and micro aggregation), rotational thromboelastometry and Platelet Function Analyzer 200.ResultsWe found no significant difference in mean platelet volume and immature platelet fraction and no difference in platelet activation as measured by exposure of CD62P, CD63P and PAC1 binding. Nor did we find a significant difference in platelet aggregation response in HHT-patients compared with the control group for all agonists (thrombin receptor activating peptide, adenosine diphosphate and collagen-related peptide). The PFA-200 analysis was without difference between the two groups and thromboelastometry showed no impairment of global haemostasis.ConclusionReduced platelet function is unlikely to contribute to the frequent and long bleeding episodes that HHT-patients suffer from. We propose that further studies should focus on whether patients with HHT have hypercoagulability.

Risk Factors and Management Outcomes in Pediatric Epistaxis at an Emergency Department

BackgroundMost cases of pediatric epistaxis are spontaneous and self-resolve. However, a subset of children may experience significant bleeding and require procedural or medical intervention. ObjectiveWe aim to identify risk factors associated with moderate and severe epistaxis in the emergency department (ED) and explore management outcomes. MethodsWe retrospectively reviewed all patients under 22 years old with epistaxis who presented to our ED between 2013 and 2022. Epistaxis severity was defined as mild (required nasal compression or intranasal medications), moderate (required cautery or packing), or severe (required factor replacement, transfusion, hospital admission, or surgery). We performed univariable and multinomial regression analyses, with risk factors and outcomes analyzed according to severity. ResultsOf 858 visits, 41 (5%) patients had moderate and 67 (8%) had severe epistaxis. Patients with moderate epistaxis were older than those with mild and severe epistaxis (median 15.6 vs. 8.3 vs. 10.7 years, p < 0.001). In regression analysis, moderate epistaxis was associated with older age, prior ED visit within 72 h, and antiplatelet medication use (p < 0.01). Severe epistaxis was associated with bleeding disorders, nasal procedures within 30 days, and anticoagulation medication use (p ≤ 0.001). Bleeding over 30 min prior to arrival was associated with both moderate and severe epistaxis (p < 0.05). Of the 67 patients with severe epistaxis, 10 (15%) required factor replacement, 28 (42%) required transfusion, 52 (77%) required hospital admission, and 5 (7%) underwent surgery. ConclusionEpistaxis severity is associated with certain risk factors. However, most cases of pediatric epistaxis are mild and do not require intervention or ED evaluation.

Assessing the Psychometric Validity of the Epistaxis Severity Score: Internal Consistency and Test-Retest Reliability.

The Epistaxis Severity Score (ESS) is the gold-standard patient-reported outcome measure for evaluating nosebleed severity in patients with hereditary hemorrhagic telangiectasia (HHT). To date, the ESS has been assessed only for content validity and concurrent validity. We evaluate the internal consistency and test-retest reliability of the ESS. After receiving institutional review board approval, we sent an online survey battery, including the ESS survey, to 305 (39% male) English-speaking HHT patients ≥18 years old at a single center. Of those, 140 (46%) patients completed the battery, and 110/140 (79%) reported epistaxis. Cronbach's alpha and correlation analyses were used to evaluate internal consistency. For the test-retest reliability evaluation, we recruited 69 HHT patients during HHT clinic to complete 2 self-administered ESS surveys 2 weeks apart. Participants also completed a modified Clinical Global Impression-Improvement scale with readministration of the ESS survey. We calculated the intraclass correlation coefficient in a 2-way mixed model with absolute agreement. The ESS survey demonstrated low internal consistency (Cronbach's alpha = 0.495), suggesting that it measured multiple unrelated concepts. Factor analysis revealed 3 latent factors with moderate intercorrelation, suggesting the presence of 3 related but distinct constructs underlying the ESS. However, the ESS demonstrated excellent test-retest reliability (intraclass correlation coefficient = 0.955; 95% CI, 0.91-0.98). Although the ESS demonstrates high test-retest reliability, it may not adequately assess different dimensions of nosebleed severity. Additional correlated survey questions and sub-scores may be needed to increase internal consistency to accurately measure each component of epistaxis severity. It is necessary to acknowledge epistaxis severity from different dimensions and to consider evaluating individual ESS items separately for a comprehensive understanding.

Factors affecting Naseptin treatment success - A prospective cohort study.

To assess patient factors to predict treatment success of Naseptin for recurrent paediatric epistaxis. This prospective cohort study of paediatric patients referred to a tertiary paediatric otolaryngology clinic with recurrent epistaxis treated with Naseptin cream and education. Patients with red flag symptoms and bleeding diathesis were omitted, along with patients with concurrent otolaryngology complaints. Statistical analysis included logistic regression analysis to assess for predictive factors contributing to treatment success. 125 of 210 patients on the waiting list met the inclusion criteria and were given a complete trial of Naseptin. 80.8% (n=101) of patients found that the frequency and severity of epistaxis had reduced, with the remaining 19.2% (n=24) reporting that the episodes of epistaxis remained the same and required further management (i.e., silver nitrate cautery). Five patients (4%) reported minor side effects (skin irritation etc.) with no significant adverse events reported. We found that Naseptin is a safe, well-tolerated treatment that should be trialled in most cases of recurrent paediatric epistaxis. Most children will benefit from it with complete epistaxis cessation or at least reduced frequency and severity.

Unsupervised machine learning algorithms identify expected haemorrhage relationships but define unexplained coagulation profiles mapping to thrombotic phenotypes in hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) can result in challenging anaemia and thrombosis phenotypes. Clinical presentations of HHT vary for relatives with identical casual mutations, suggesting other factors may modify severity. To examine objectively, we developed unsupervised machine learning algorithms to test whether haematological data at presentation could be categorised into sub-groupings and fitted to known biological factors. With ethical approval, we examined 10 complete blood count (CBC) variables, four iron index variables, four coagulation variables and eight iron/coagulation indices combined from 336 genotyped HHT patients (40% male, 60% female, 86.5% not using iron supplementation) at a single centre. T-SNE unsupervised, dimension reduction, machine learning algorithms assigned each high-dimensional datapoint to a location in a two-dimensional plane. k-Means clustering algorithms grouped into profiles, enabling visualisation and inter-profile comparisons of patients' clinical and genetic features. The unsupervised machine learning algorithms using t-SNE and k-Means identified two distinct CBC profiles, two iron profiles, four clotting profiles and three combined profiles. Validating the methodology, profiles for CBC or iron indices fitted expected patterns for haemorrhage. Distinct coagulation profiles displayed no association with age, sex, C-reactive protein, pulmonary arteriovenous malformations (AVMs), ENG/ACVRL1 genotype or epistaxis severity. The most distinct profiles were from t-SNE/k-Means analyses of combined iron-coagulation indices and mapped to three risk states - for venous thromboembolism in HHT; for ischaemic stroke attributed to paradoxical emboli through pulmonary AVMs in HHT; and for cerebral abscess attributed to odontogenic bacteremias in immunocompetent HHT patients with right-to-left shunting through pulmonary AVMs. In conclusion, unsupervised machine learning algorithms categorise HHT haematological indices into distinct, clinically relevant profiles which are independent of age, sex or HHT genotype. Further evaluation may inform prophylaxis and management for HHT patients' haemorrhagic and thrombotic phenotypes.

Exploring effects of atmospheric conditions in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations. Individuals with HHT often identify low humidity and temperature as detrimental to epistaxis severity. We set out to assess the relationship between humidity and temperature on epistaxis severity in patients with HHT. Retrospective cross-sectional study at an academic hospital with an HHT center between July 1, 2014 and January 1, 2022. The primary outcome of this study was ESS. Pearson correlation analyses and multiple linear regression analyses were performed to test the association between weather variables and epistaxis severity scre (ESS). Results were reported as coefficient and 95% confidence interval (CI). Four hundred twenty-nine patients were included in the analysis. Through a Pearson correlation analysis, neither humidity (regression coefficient=-0.01; 95% CI,-0.006 to 0.003; p=0.50), daily low temperature (regression coefficient=0.01; 95% CI,-0.011 to 0.016; p=0.72), or daily high temperature (regression coefficient=0.01; 95% CI,-0.004 to 0.013; p=0.32) were significantly correlated with ESS. In a multiple linear regression analysis, adjusting for both daily low temperature and humidity, medications taken, demographics, and genotype, neither daily low temperature (regression coefficient=-0.02; 95% CI,-0.04 to 0.01; p=0.14) nor humidity (regression coefficient=0.01; 95% CI,-0.01 to 0.01; p=0.64) were significantly associated with ESS. We have shown in a large clinical sample that neither humidity nor temperature were strongly correlated with HHT patient epistaxis severity.

Silicone septal splint for recurrent epistaxis in HHT patients: experience of a national referral centre.

To report our experience in the use of silicone septal splint for recurrent severe epistaxis in hereditary haemorrhagic telangiectasia patients (HHT). This is a descriptive analysis carried out at the Otorhinolaryngology Department of Fondazione IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent silicone septal splint positioning after the endoscopic surgical treatment of epistaxis from 2000 to 2022. Of the 506 patients surgically treated in the period of analysis, 74 patients underwent silicone septal splint positioning and 37 were post-operatively interviewed. With a mean of 2.4 previous surgical treatments and a mean epistaxis severity of 7.38, the majority of patients presented with septal perforation (71.6%). On average, patients maintained the splint in place for 54.5 months, with a good tolerability and a significant reduction in epistaxis severity, need for blood transfusion and improvement of haemoglobin levels. In HHT patients with recurrent severe epistaxis and with septal perforation, the placement of septal splints offers a useful additional strategy in the management of nosebleeds.

Surgiflo® hemostatic matrix versus NasoPore® nasal packing following postassium titanyl phosphate laser surgery for hereditary hemorrhagic telangiectasia: A randomized controlled trial.

To help ensure adequate hemostasis immediately following potassium titanyl phosphate (KTP) laser treatment, many centres treating hereditary hemorrhagic telangiectasia (HHT) routinely use nasal packing post-operatively. The purpose of this study was to compare hemostatic thrombin matrix with standard packing for postoperative bleeding, patient pain, and comfort. A prospective, randomized, double-blinded, non-inferiority study was conducted with participants at an HHT centre of excellence (COE) and randomized to the treatment group with reconstituted thrombin gelatin matrix (Surgiflo®) or control group with a biodegradable synthetic polyurethane foam (NasoPore®). Adult subjects with confirmed HHT and moderate to severe epistaxis (a minimum calculated epistaxis severity score [ESS] of 4.0) warranting KTP laser treatment were recruited. Data was collected 2 weeks post operatively by a blinded reviewer completing a visual outcomes evaluation and each patient completing a subjective symptoms questionnaire. Non-parametric statistical analysis was employed. Twenty-eight adult patients were randomized to the treatment and control arms with comparable preoperative epistaxis severity scores. Postoperative nasal bleeding was equivalent. Significantly less pain was found in the treatment arm (p=.005). While there were trends towards less obstruction and increased satisfaction in the treatment group as well as less crusting in the control group, these findings were not statistically significant. Allocation to the treatment group was associated with an approximately $75 higher cost. When compared to NasoPore® for hemostasis, Surgiflo® hemostatic matrix performed equivalently while causing less discomfort in HHT patients following nasal KTP treatment. 1b.