The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care.

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.

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.

Nasal self-packing for epistaxis in Hereditary Hemorrhagic Telangiectasia increases quality of life.

STATEMENT OF PROBLEM: Hereditary hemorrhagic telangiectasia (HHT) is characterized by recurrent epistaxis that can lead to a feeling of losing control. We assessed potential benefits and side effects of different nasal packings used by patients themselves. METHOD OF STUDY: An online-questionnaire in English and German was used to analyze nasal self-packings. RESULTS: 588 of the 915 respondents suffered from HHT with most of them having moderate or severe epistaxis. Almost two thirds of the patients had already treated themselves with nasal packings. While one quarter used non-pneumatic nasal packings (NPNP) or pneumatic nasal packings (PNP), nearly half of the patients took only tissues to stop the bleeding. Patients with severe epistaxis used PNP more often than NPNP. Using nasal packings, most patients could stop their nosebleeds after a while. Patients using PNP reported the feeling of losing control less often and significant improvements in quality of life with a positive GBI. CONCLUSIONS: Our study showed that most patients with HHT using nasal self-packings could stop the bleeding after a while. Nasal self-packing is a user-friendly and secure method leaving patients more self-confident and independent.

Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) can be found in patients suffering from a loss-of-function mutation of the gene encoding for the activin receptor-like kinase 1 (ALK-1), a bone morphogenetic protein (BMP) type 1 receptor. Interestingly, ALK-1 mutations also lead to hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease characterized by arteriovenous malformations (AVMs) leading to potentially life-threatening bleeding complications such as epistaxis. Current therapeutic options for both diseases are limited and often only temporary or accompanied by severe side effects. Here, we report of a patient with a mutation of the ALK-1 gene suffering from both HHT and PAH. Recently, it was shown that tacrolimus increased ALK-1 signaling and had beneficial effects in selected end-stage PAH patients. We thus hypothesized that treatment with tacrolimus may prevent disease progression in this patient. Surprisingly, treatment with low-dose tacrolimus dramatically improved his HHT-associated epistaxis but did not attenuate progression of PAH.

[Assessing activities of daily living in patients with epilepsy]. / Die Erfassung von Aktivitäten des täglichen Lebens (ADL) bei Epilepsie.

BACKGROUND: Objective cognitive assessment and subjective self-assessment do not sufficiently reflect actual daily routines and everyday functioning of patients with epilepsy. The study at hand examined whether a questionnaire assessing the activities of daily living provides additional diagnostic information. METHODS: A total of 180 consecutive patients with epilepsy received a questionnaire addressing (i) mood, (ii) subjective cognitive performance as well as (iii) frequencies of subjective problems in everyday life and (iv) 36 activities of daily living (ADL-Track). Normative data were based on 536 healthy volunteers. Analysis focused on the interrelation among these subjective measures as well as their relation to objective neuropsychological performance. RESULTS: Compared to the normative sample, social activities, home activities, and mobility were reduced in 25 - 34 % of the patients (OR = 2.07 - 2.79). Frequencies of activities of daily living reflect the results of subjective performance ratings ("attention", "praxia") and objective performance in attention, language, intelligence and memory. A negative mood showed highly significant correlations with subjective complaints and increased the risk of reduced activities by a factor of 2 - 3. Multiple regression analyses explained between 9 - 22 % of the variance of the ADL-Track scales. CONCLUSION: The ADL-Track, a questionnaire on frequencies of activities of daily living, appears more independent from mood than subjective complaints and it shows relevant correlations with subjective and even more with objective cognitive measures. Moreover, it indicates a behavioural domain in epilepsy which is not yet covered by standard diagnostics. When applied longitudinally, the ADL-Track may well turn out to be a valuable longer-term outcome parameter with regard to epilepsy and its treatment.