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Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications.METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved.RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Despite being a hemorrhagic condition, patients with hereditary hemorrhagic telangiectasia (HHT) are at increased thromboembolic risk. We designed an observational retrospective cohort study of HHT patients who required anticoagulation therapy, described their indications and adverse events. From January 2006 until August 2019 28 out of 347 adult HHT patients received anticoagulant drugs for a median of 0.5 years (IQR 0.2–4.1). Median age was 64 years (IQR 51–70), all of the patients had epistaxis and at least one arteriovenous malformation. Fourteen (50%) patients received anticoagulants due to venous thromboembolic disease and 6 (21.4%) for atrial fibrillation. Nine patients (32.1%) received low-molecular-weight heparin and 19 (67.9%) vitamin-K antagonists. Seven (25%) withdrew treatment due to increased bleeding frequency from usual sites and 5 (17.9%) had a major bleeding event. Ten (35.7%) patients completed short length anticoagulation without significant adverse events.

Corona virus disease (COVID-19) presents a serious threat to global health. A historical timeline of early molecular diagnostics from government alert (January 22) (D) was presented. After in silico analysis, Brazilian Army Institute of Biology (IBEx-RJ) tested samples in house using real-time reverse transcriptase polymerase chain reaction (RT-PCR) (fast mode) based on Centers for Disease Control and Prevention (CDC) recommendations. First cases from Brazil, Rio de Janeiro, IBEx, and diagnosis team were reported in D36, D44, D66, and D74 respectively. Therefore, after 1300 tests, we recommend N1/N2 primer sets (CDC) for preliminary and Charite protocol confirmation in case of positive results. Moreover, every professional should be tested before starting work, in addition to weekly tests for everyone involved.

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder that causes chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHTassociated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, Epistaxis Severity Score (ESS), red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. Bevacizumab was given to 238 HHT patients for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% confidence interval: 2.9-3.5 g/dL); i.e., from a mean hemoglobin of 8.6 (8.5-8.8) g/dL to 11.8 (11.5-12.1) g/dL; P

Objective To report our clinical experience with bevacizumab in a cohort of Hereditary Hemorrhagic Telangiectasia (HHT) patients with severe hepatic involvement and/or refractory anemia. Methods Observational, ambispective study of the Institutional Registry of HHT at Hospital Italiano de Buenos Aires. Patients were treated with bevacizumab due to iron deficiency refractory anemia secondary to nasal/gastrointestinal bleeding and/or high output cardiac failure. We describe basal clinical data, bevacizumab schedules, efficacy outcomes and adverse events. Wilcoxon signed ranks test and longitudinal analysis were conducted. Results Twenty adult patients were included from July 2013 to June 2019. Clinical indications were: 13 for anemia, 4 for heart failure and 3 for both. In the anemia group, median pretreatment hemoglobin was 8.1 g/dl [IQR: 7.2–8.4] and median transfusion requirement was 4 units [2–6]. In heart failure group, pretreatment median cardiac index was 4.5 L/min/m2 [4.1–5.6] and cardiac output was 8.3 L/min [7.5–9.2]. Bevacizumab 5 mg/kg/dose every 2 weeks for 6 applications was scheduled. By the end of induction, median hemoglobin at 3 months was 10.9 g/dl [9.5–12.8] (p = 0.01) and median transfusion requirement 0 units [0–1] (p

Hereditary hemorrhagic telangiectasia (HHT) usually presents in association with pulmonary arteriovenous malformations (PAVMs). In addition, the incidence of venous thromboembolism tends to be increased in these patients. A 74-year-old female with HHT presented with cyanosis and hypoxemia. Contrast-enhanced multislice computed tomography (MSCT) revealed two left PAVMs and one in the right upper lobe. Both left PAVMs were treated with embolotherapy. Follow-up MSCT revealed an incidental pulmonary embolism in the right pulmonary branches. Deep venous thrombosis was confirmed and anticoagulation was initiated. Follow-up MSCT revealed the resolution of thromboembolism. Finally, embolotherapy was performed. This case illustrates the chronic adaptation to hypoxemia and adds further evidence to the relative safety of anticoagulation treatment in these patients.

Background Around 47–74% of patients with hereditary hemorrhagic telangiectasia (HHT) have hepatic vascular malformations (HVMs); magnetic resonance images (MRI) of the central nervous system (CNS) might show in T1 sequences a hyper-intensity signal in different areas, mainly in the basal ganglia (BG) as consequence of manganese (Mn) deposits as observed in cirrhotic patients. These patients might suffer from different neuropsychiatric disorders (hepatic encephalopathy). In HHT patients, even in the presence of hepatic shunts, hepatocellular function is usually preserved. Additionally, Mn shares iron absorption mechanisms, transferrin and CNS transferrin receptors. In iron deficiency conditions, the Mn may harbor transferrin and access BG. The objectives were to describe frequency of BG Mn deposit-induced lesions (BGMnIL) in HHT patients, its relationship with iron deficiency anemia (IDA) and HVMs. Finally, explore the association between neuropsychological and motor consequences. We performed a cross-sectional study. We determined HHT patients with or without BG-MnIL by the MRI screening of the CNS. We included all patients with lesions and a random sample of those without lesions. All patients underwent standardized and validated neuropsychological assessment to evaluate BG actions. Results were analyzed with multiple logistic regression, adjusting for potential confounders. Results Among 307 participants from a cohort included in the Institutional HHT Registry, 179 patients had MRI performed and Curaçao Criteria ≥3. The prevalence of BG-MnIL was 34.6% (95%CI 27.69-42.09). While neuropsychological symptoms were present in all patients, BG-MnIL patients performed poorly in three of the neuropsychological tests (serial dotting, line tracing time, number connection test A). HVMs frequency in BG-MnIL was 95.1%, versus 71.4% in those without lesions (p

Patients with hereditary hemorrhagic telangiectasia (HHT) and pulmonary arteriovenous malformation (PAVM) face higher risk of embolic complications. It is not clear whether poor outcomes are related to PAVM severity or pulmonary symptoms. Furthermore, there is currently no available data on HHT patients in Argentina. We conducted a cross sectional study in a teaching hospital in Buenos Aires, Argentina. We describe baseline characteristics of HHT and compare the prevalence of embolic complications in patients with significant PAVM compared to patients without significant PAVM. One hundred and eight consecutive patients were included. Significant PAVM was defined as: contrast echocardiography grade 2 or greater; bilateral PAVM or feeding artery bigger than 3mm; or previous PAVM treatment. Primary composite outcome was defined as: cerebrovascular accident, cerebral abscess or peripheral embolism. 20% of participants had embolic complications, the most frequent one was stroke. Embolic complications were associated with significant PAVM and respiratory symptoms.

Resumen Los pacientes con telangiectasia hemorragica hereditaria (THH) y malformacion arteriovenosa pulmonar (MAVP) afrontan un riesgo mas elevado de complicaciones embolicas. No esta claro si la mala evolucion clinica esta relacionada con la gravedad de la MAVP o con los sintomas pulmonares. Ademas, en la actualidad no disponemos de datos de pacientes con THH en Argentina. Llevamos a cabo un estudio transversal en un hospital universitario de Buenos Aires, Argentina. Describimos aqui las caracteristicas basales de la THH y comparamos la prevalencia de complicaciones embolicas en pacientes con una MAVP significativa frente a la de los pacientes sin una MAVP significativa. Un total de 108 pacientes consecutivos fueron incluidos en el estudio. La MAVP significativa se definio de la siguiente forma: ecocardiografia con contraste de grado 2 o superior; MAVP bilateral o aferencia de mas de 3 mm, o tratamiento previo de la MAVP. La variable de valoracion combinada primaria se definio como: accidente cerebrovascular, absceso cerebral o embolia periferica. Un 20% de los participantes presento complicaciones embolicas, la mas frecuente de las cuales fue el ictus. Las complicaciones embolicas se asociaron a una MAVP significativa y sintomas respiratorios.

Introduction : Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare hereditary multisystem vascular disease of disordered angiogenesis. Pathologic elevations in vascular endothelial growth factor (VEGF) result in fragile, abnormal vessels in nasal and gastrointestinal (GI) mucosa causing recurrent epistaxis, chronic GI bleeding, and anemia that is often transfusion-dependent. Bevacizumab is a monoclonal IgG1 antibody that neutralizes circulating VEGF and is a potential targeted anti-angiogenic treatment in HHT, which has no FDA-approved therapy. Data for use of intravenous (IV) bevacizumab in HHT is currently limited to case reports and small single-center retrospective case series. The International HHT Intravenous Bevacizumab Investigative Team study of Bleeding (InHIBIT-Bleed) is an international collaboration of HHT Centers seeking to more definitively describe the safety and effectiveness of systemic bevacizumab to treat chronic bleeding and anemia in HHT. Methods : The following data was retrospectively collected at each participating center for all HHT patients treated for at least 3 months with off-label systemic bevacizumab for chronic bleeding: demographics, baseline HHT characteristics, epistaxis severity score (ESS, a validated 10-point scale to evaluate epistaxis in HHT), bevacizumab dosing, treatment-emergent adverse events (TEAEs), hemoglobin (Hgb), red blood cell (RBC) transfusions, and IV iron infusions. Hgb and ESS at baseline were compared with post-bevacizumab values at 3, 6, 9, and 12 months with the paired t-test. RBC transfusion and iron infusion requirements before and after bevacizumab treatment were compared with the Wilcoxon signed rank test. Results : 140 HHT patients were treated with IV bevacizumab for chronic bleeding for a median of 23 (range, 3-96) months with a median of 12 (range, 2-74) total infusions. Bevacizumab was dosed at 5 mg/kg every 2 weeks for the first 2 months, then monthly for 4 months; following this, maintenance dosing practices varied depending on center. Baseline patient characteristics are given in Table 1. After bevacizumab initiation, patients with baseline anemia (Hgb Conclusions : We present results of IV bevacizumab treatment of chronic bleeding and anemia in a large cohort of 140 HHT patients, demonstrating that bevacizumab was highly effective, with an improvement in mean Hgb of 3.9 g/dL, dramatic reduction in ESS, and decrease in RBC transfusion and iron infusion requirements by 86% and 66%, respectively. Effectiveness was maintained over time. Safety analysis included a total of 194 patient-years of IV bevacizumab administration to HHT patients and had low TEAE rates with only 4% discontinuing treatment due to TEAEs. Disclosures Al-Samkari: Agios: Consultancy, Research Funding; Moderna: Consultancy; Dova: Consultancy, Research Funding. Kuter:Caremark: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Dova: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Zafgen: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria; Shinogi: Consultancy, Honoraria; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Agios: Consultancy, Honoraria, Research Funding; Platelet Disorder Support Association: Consultancy, Honoraria; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Caremark: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Merck Sharp Dohme: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Argenx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Kezar: Research Funding; Shire: Consultancy, Honoraria; Kezar: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Principia: Consultancy, Honoraria, Research Funding; Zafgen: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Principia: Consultancy, Honoraria, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Protalix: Consultancy, Honoraria; Protalix: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Rigel: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; UCB: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Protalex: Consultancy, Honoraria, Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Shinogi: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Dova: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Momenta: Consultancy, Honoraria. OffLabel Disclosure: The presentation will discuss off-label use of systemic bevacizumab for the treatment of chronic bleeding and anemia in hereditary hemorrhagic telangiectasia.

The Hereditary Hemorrhagic Telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia that affects 1-5000 individuals worldwide. Is characterized by fragile mucocutaneous telangiectasia and vascular malformations in organs such as brain, lungs, liver and the gastrointestinal tract. Nose and gastrointestinal bleeding are remarkable, leading to frequent iron deficiency anemia (IDA) or life threatening bleeding episodes. Venous thromboembolic events (VTE) in HHT are probably more frequent than general population due to high plasmatic levels of FVIII specially in clinical conditions like long time immobilization due to brain abscesses or severe anemia. Additionally, in those patients with pulmonary fistula, the thromboembolic events can produce paradoxal strokes. On the other hand, almost all HHT medical treatments usually used to treat HHT related bleeding could produce thromboembolic disease. Anticoagulation (ACO) in this bleeding condition is a challenge, nevertheless, almost 50% can tolerate it well. Objective: To report the incidence of VTE in the HHT population. Methods: Ambispective cohort of adult based on the Institutional Registry of HHT. VTE was defined as the first episode of pulmonary embolism (PE), deep venous thrombosis (VTE) or thrombosis in the fistula sac or the progression of a prior event after its first 48 hs despite anticoagulation. Result: Over 524 patients 394 adults with HHT confirmed by Curazao criteria or positive genetic test and complete data were included. There were 18 VTE events 4.6% (CI95% 2.7-6.8%), 9 DVT (2.3% IC95% 1.2-4.4%) and 3 PE (0.7% IC95% 0.13-2%). The female gender represents 72%. The median age at the event was 67 years (IIQ 25-75% 56-73). Five patients (27%) were on ACO prior to the event, mainly for atrial fibrillation, and 3(18%) suffered a previous VTE. The most frequent risk factors were recent hospitalization (44%) and iron deficiency anemia (44%), immobility (33%), recent surgery (18%), as well as cancer (5%) and recent travel (5%) patient each.Fifteen (83%) patients received ACO, 10(55%) received LMH followed by acenocumarol, 3(30%) of which had to be stopped due to nose or gastrointestinal bleeding.In 5 (27%) a cava vein filter were inserted, of which 3 are under anticoagulation therapy. Conclusion: VTE incidence in our study was significantly higher than reported in general population at similar age. However, the inclusion of more symptomatic and serious HHT patients could be selection bias. The low number of patients, may influence the results. IDA and hospitalization were the most important associated conditions. Most patients tolerated well the anticoagulation therapy. Disclosures No relevant conflicts of interest to declare.

The recent generation of AMPLATZER Vascular Plug (AVP; ie, the AVP IV) was used for the occlusion of eight pulmonary arteriovenous malformations (PAVMs) in five patients. A treatment was considered successful when there was a reduction or disappearance of the aneurysmal sac. At a mean follow-up of 20.1 months, no recanalization of PAVMs was observed on multidetector computed tomographic angiography. This shows the AVP IV to be safe and effective as an embolic device to occlude PAVMs.

Patients with hereditary hemorrhagic telangiectasia (HHT) and pulmonary arteriovenous malformation (PAVM) face higher risk of embolic complications. It is not clear whether poor outcomes are related to PAVM severity or pulmonary symptoms. Furthermore, there is currently no available data on HHT patients in Argentina. We conducted a cross sectional study in a teaching hospital in Buenos Aires, Argentina. We describe baseline characteristics of HHT and compare the prevalence of embolic complications in patients with significant PAVM compared to patients without significant PAVM. One hundred and eight consecutive patients were included. Significant PAVM was defined as: contrast echocardiography grade 2 or greater; bilateral PAVM or feeding artery bigger than 3mm; or previous PAVM treatment. Primary composite outcome was defined as: cerebrovascular accident, cerebral abscess or peripheral embolism. 20% of participants had embolic complications, the most frequent one was stroke. Embolic complications were associated with significant PAVM and respiratory symptoms.

In August, 2011, an 83-year-old woman presented to our emergency department with several days of diff use persistent abdominal pain. She also reported an episode of lower gastrointestinal bleeding with symptoms of orthostasis. She had a history of cardiac failure, pulmonary hypertension, and epistaxis of un known cause. On initial physical examination she was haemodynamically stable without signs of acute ab dom inal disease. She had oral mucocutaneous telangiectases. Gastric lavage was done, and no evidence of upper gastrointestinal bleeding was seen. Blood tests showed a haematocrit concentration reduction from 25% to 20%, and a haemoglobin of 69 g/L. She was admitted for blood transfusion and assessment. After 5 days, she developed acute abdominal pain, tachycardia (135 beats per min), and hypotension (80/40 mm Hg). Sonography of the abdomen showed a large amount of free abdominal fl uid. Multi-detector computed tomography (MDCT) of the abdomen and pelvis confi rmed intra-abdominal fl uid and also showed liver arteriovenous malformations. CT-guided paracentesis confi rmed a diagnosis of haemo peritoneum. An emergency surgical exploration of the abdominal cavity was done because of her poor clinical condition. Explor ation showed haemo peritoneum and a portal vein branch with active bleeding due to the vascular malformations (fi gure). Haemostatic suturing was done to stop bleeding, and the abdominal cavity was drained. She had an uneventful postoperative course and was discharged at postoperative day 10. At last follow-up in Lancet 2013; 381: 962