Quality of life in patients with hereditary haemorrhagic telangiectasia (HHT)

Background: There are very few studies about general quality of life parameters, standards for the description of health status and comparison with general population data on patients with Hereditary hemorrhagic telangiectasia (HHT), a rare disease in which epistaxis is a cardinal symptom. Purpose: To assess the quality of life in a population of Spanish patients with HHT and compare it with the general population. Design and methods: Between January 1st 2005 and December 31st 2013, 187 adult patients diagnosed with HHT who were admitted to the HHT Unit of the Hospital Sierrallana, completed on their first visit, the EuroQol 5D-3L (five dimensions and three levels) quality of life descriptive test and the visual analog scale (VAS). The numerical social index value was also determined and the subjective effect of the nasal epistaxis on their quality of life was estimated classified as mild, moderate or severe. Results: Patients with HHT had greater problems than the general population in the five dimensions of the EuroQol 5D-3L, particularly considering pain/discomfort and anxiety/depression. In the VAS and the social index value, patients with HHT also scored lower than the general population, particularly older patients, males, and patients with HHT2. They also had values similar to those of populations with chronic illnesses. The subjective perception of the severity of epistaxis correlated strongly with the VAS and social index values. Conclusions: The quality of life of patients with HHT, estimated using the EuroQol 5D-3L scale, is affected across all dimensions. The scores are similar to those seen in cases of other chronic diseases. Older patients, males and the carriers of the ACVRL1 mutation generally have worse scores on these scales. The VAS and the social index value are index that correlate well with the severity of the clinical symptoms associated mainly with epistaxis

Can iron treatments aggravate epistaxis in some patients with hereditary hemorrhagic telangiectasia?

Objectives/Hypothesis To examine whether there is a rationale for iron treatments precipitating nosebleeds (epistaxis) in a subgroup of patients with hereditary hemorrhagic telangiectasia (HHT). Study Design Survey evaluation of HHT patients, and a randomized control trial in healthy volunteers. Methods Nosebleed severity in response to iron treatments and standard investigations were evaluated by unbiased surveys in patients with HHT. Serial blood samples from a randomized controlled trial of 18 healthy volunteers were used to examine responses to a single iron tablet (ferrous sulfate, 200 mg). Results Iron tablet users were more likely to have daily nosebleeds than non–iron-users as adults, but there was no difference in the proportions reporting childhood or trauma-induced nosebleeds. Although iron and blood transfusions were commonly reported to improve nosebleeds, 35 of 732 (4.8%) iron tablet users, in addition to 17 of 261 (6.5%) iron infusion users, reported that their nosebleeds were exacerbated by the respective treatments. These rates were significantly higher than those reported for control investigations. Serum iron rose sharply in four of the volunteers ingesting ferrous sulfate (by 19.3–33.1 μmol/L in 2 hours), but not in 12 dietary controls (2-hour iron increment ranged from −2.2 to +5.0 μmol/L). High iron absorbers demonstrated greater increments in serum ferritin at 48 hours, but transient rises in circulating endothelial cells, an accepted marker of endothelial damage. Conclusions Iron supplementation is essential to treat or prevent iron deficiency, particularly in patients with pathological hemorrhagic iron losses. However, in a small subgroup of individuals, rapid changes in serum iron may provoke endothelial changes and hemorrhage

Family planning, sexual activity and contraception in hereditary hemorrhagic telangiectasia:a European survey study

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) can influence the quality of life and social relationships, mostly due to epistaxis, but the topics of family planning, sexual activity and contraception have not been investigated to date. This study aimed to gain more insight: what is the influence of HHT on family planning, sexual activity and contraception? METHODS: This multi-language European survey study included a patient's and partners' version of a questionnaire designed specifically for this study. HHT patients were informed about the study through HHT expert centres, social media and websites of patient associations. Data collection took place between March- May 2023. RESULTS: The survey was completed by 572 patients with a definite HHT diagnosis, based on genetic confirmation or ≥ 3 Curaçao criteria. In most patients, HHT did not affect relationship decisions (n = 353, 62%), decisions concerning pregnancy and children (n = 287, 50%) and sexual activity (n = 315, 57%). However, 28% of HHT patients (n = 157) did experience effect on sexual activity and may benefit from improved epistaxis management and better awareness of their partners. CONCLUSIONS: HHT did not affect family planning decisions and sexual activity in most patients, but approximately a quarter of patients experienced effect on sexual activity caused by epistaxis.</p

Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia

Background: Hereditary haemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anaemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolismand/or atrial fibrillation. Over decades,tolerance data has been publishedfor almost 200HHT-affected usersof warfarinand heparins, but there are no publisheddata forthe newer direct oralanticoagulants(DOACs)in HHT. Methods: To provide such data, aretrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Vascular Disorders (VASCERN),in Denmark, France, Germany, Italy, Netherlands and UK. Results: Although HHT Centreshad not specifically recommended the use of DOACs, 32treatment episodes had been initiated by other cliniciansin 28patients reviewed at the centres, at median age 65years(range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes).The 32 treatment episodes used Apixaban (n=15), Rivaroxaban (n=14), and Dabigatran (n=3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15(26.7%) Apixabanepisodes and 7/14 (50%)Rivaroxaban episodes.By a 4 point scale of increasing severity,there was a trend for Rivaroxaban to be associated with a greaterbleeding riskboth including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associationswere maintained after adjustment for genderand treatment indication. Extreme haemorrhagic responses, worse thananything experienced previously, with individual nosebleedslasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in5/14(35.7%) Rivaroxabanepisodes compared to 3/15(20%) Apixabanepisodes and published rates of ~5% for warfarin and heparin. Conclusions: Currently, conventional heparin and warfarin remain first choice anticoagulantsin HHT. If newer anticoagulants are considered,although study numbers are small, at this stage Apixaban appearsto be associated with lesser bleeding riskthan Rivaroxaban

Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT. Methods: To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK. Results: Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin. Conclusions: Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.</p

Ocular lesions in hereditary hemorrhagic telangiectasia: genetics and clinical characteristics

Background: The aim of our study is to study the association between eye lesions in Hereditary Hemorrhagic Telangiectasia (HHT) and other signs of the disease, as well as to characterize its genetics. Methods: A cross-sectional study was conducted of a cohort of 206 patients studied in the HHT Unit of Hospital de Sierrallana, a reference centre for Spanish patients with HHT. Odds ratios for several symptoms or characteristics of HHT and ocular lesions were estimated using logistic regression adjusting for age and sex. Results: The ocular involvement was associated with being a carrier of a mutation for the ENG gene, that is, suffering from a type 1 HHT involvement (OR = 2.09; 95% CI [1.17–3.72]). p = 0.012). In contrast, patients with ocular lesions have less frequently mutated ACVRL1/ALK1 gene (OR = 0.52; 95% CI [0.30–3.88], p = 0.022). Conclusions: In conclusion, half of the patients with HHT in our study have ocular involvement. These eye lesions are associated with mutations in the ENG gene and ACVRL1/ALK1 gene. Thus, the ENG gene increases the risk of ocular lesions, while being a carrier of the mutated ACVRL1/ALK1 gene decreases said risk

Development of the First Force-Controlled Robot for Otoneurosurgery

Objective: In some surgical specialties, e.g. orthopedics, robots are already used in the operating room for bony milling work. Oto- and otoneurosurgery may also greatly benefit by robotic enhanced precision. Study Design: Experimental study on robotic milling on oak wood and human temporal bone specimen. Methods: A standard industrial robot with a 6 degrees-of-freedom serial kinematics was used with force feedback to proportionally control the robot speed. Different milling modes and characteristic path parameters were evaluated to generate milling paths based on CAD geometry data of a cochlear implant and an implantable hearing system. Results: The best suited strategy proofed to be the spiral horizontal milling mode with the burr held perpendicularly to the temporal bone surface. In order to avoid high grooves, the distance in between paths should equal half the radius of the cutting burr head. Due to the vibration of the robot’s own motors, a rather high oscillation of the standard deviation of forces was encountered. This oscillation dropped drastically to nearly 0 N, when the burr head reached contact with the dura mater due to its damping characteristics. The cutting burr could be moved a long time on the dura without damaging it, because of its rather blunt head. The robot moved the burr very smoothly according to the encountered resistances. Conclusion: This is the first development of an functioning robotic milling procedure for otoneurosurgery with force-based speed control. It is planned to implement ultrasound-based local navigation and to perform robotic mastoidectomy