scholarly journals Management of Refractory Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia with Bevacizumab

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Muaaz Masood ◽  
Michael Coles ◽  
Humberto Sifuentes
Keyword(s):  
Monoclonal Antibody ◽  
Gastrointestinal Bleeding ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Autosomal Dominant ◽  
Vascular Malformations ◽  
Vascular Endothelial ◽  
Gi Bleeding ◽  
Autosomal Dominant Disorder ◽  
Recombinant Monoclonal Antibody ◽  
Endothelial Growth Factor

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder resulting in vascular malformations of several organs including the pulmonary, cerebral, and gastrointestinal systems. One sequela is recurrent gastrointestinal (GI) bleeding. Bevacizumab (Bev) is emerging as an effective treatment of recurrent gastrointestinal bleeding in HHT. Bev is a recombinant monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), an integral part of angiogenesis.

scholarly journals Bevacizumab as a treatment for hereditary hemorrhagic telangiectasia in children: a case report

2017 ◽  
pp. 88-93 ◽  
Author(s):  
Fabio E Ospina ◽  
Alex Echeverri ◽  
Iván Posso Osorio ◽  
Lina Jaimes ◽  
Jaiber Gutierrez ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Female Patient ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Pediatric Population ◽  
Adult Population ◽  
Autosomal Dominant Disorder ◽  
Arteriovenous Shunts ◽  
Clinical Benefits ◽  
Oxygen Requirements ◽  
Endothelial Growth Factor

Case description: Five-year-old female patient with hereditary hemorrhagic telangiectasia.Clinical Findings: Deterioration of cardiopulmonary function with higher oxygen requirements secondary to pulmonary arteriovenous shunts, epistaxis.Treatment and Outcome: The patient was treated with the monoclonal antibody bevacizumab, which inhibits the vascular endothelial growth factor, with good clinical outcome.Clinical Relevance: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations in different organs, making its clinical presentations varied. Systemic therapeutic options for a generalized disease are limited. The monoclonal antibody bevacizumab, seems to be a good option in this disorder. Although reported as successful in adult population, its use in pediatric population has not yet been reported. Here we report the use of bevacizumab in a 5-year-old female patient with hereditary hemorrhagic telangiectasia, showing clinical benefits and good outcome.

scholarly journals Emerging role of thalidomide in the treatment of gastrointestinal bleeding

2017 ◽  
Vol 9 (2) ◽  
pp. 98-104 ◽  
Author(s):  
Michael McFarlane ◽  
Lauren O’Flynn ◽  
Rachel Ventre ◽  
Benjamin R Disney
Keyword(s):  
Gastrointestinal Bleeding ◽  
Congenital Abnormalities ◽  
Vascular Malformations ◽  
Current Evidence ◽  
Vascular Endothelial ◽  
Antiangiogenic Effect ◽  
Vascular Abnormalities ◽  
Radiation Induced ◽  
Endothelial Growth Factor

Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

scholarly journals Bevacizumab as a treatment option in gastrointestinal bleeding associated to hereditary hemorrhagic telangiectasia. Case Report

2019 ◽  
Vol 67 (3) ◽  
pp. 343-347
Author(s):  
Erwing Castillo ◽  
Jeanette Prada-Arismendy
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Control Measures ◽  
Vascular Endothelial ◽  
Gi Bleeding ◽  
Therapeutic Choice ◽  
Life Threatening ◽  
Low Levels ◽  
Endothelial Growth Factor ◽  
The Brain ◽  
Symptomatic Control

Introduction: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disease characterized by the presence of arteriovenous malformations in the nasal mucosa, the tips of fingers, and sometimes in the lungs, the gastrointestinal tract, the liver, the pancreas, the marrow and the brain. Its treatment is based on symptomatic control measures, but recently, the administration of anti-vascular endothelial growth factor (VEGF) molecules has been proposed as a treatment alternative, especially in patients with recurrent bleeding.Case presentation: The case of a 67-year-old man diagnosed with HHT and suffering from potentially life-threatening gastrointestinal GI bleeding is presented. The patient underwent several esophagogastric cauterization procedures but not positive outcomes were obtained, so he had to go to the Emergency Service of the hospital multiple times due to having low levels of hemoglobin (as low as 3.5g/dl). A bevacizumab based treatment was started by using a novel dosage regimen consisting of the administration of 6 5mg/kg bevacizumab dosages every 14 days. During the first week of treatment, hemoglobin levels increased to 14g/dl and the condition was stabilized.Conclusions: The findings reported here suggest that bevacizumab may be a therapeutic choice to be considered when treating patients with recurrent and refractory GI bleeding caused by HHT. However, a larger sample is required to determine if administering this medication is safe for these patients, as well as the appropriate dosage.

Bevacizumab Rapidly and Completely Corrects Massive Transfusion Requirement In a Patient with Hereditary Hemorrhagic Telangiectasia (Osler Weber Rendu Syndrome)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2118-2118
Author(s):  
Donald Busiek ◽  
Keith Bernstein
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Peripheral Neuropathy ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Clinical Presentation ◽  
Transfusion Requirement ◽  
Case Reports ◽  
Aminocaproic Acid ◽  
Vascular Endothelial ◽  
Gi Bleeding ◽  
Endothelial Growth Factor

Abstract Abstract 2118 Hereditary hemorrhagic telangiectasia (HHT, Osler Weber Rendu Syndrome) is an autosomal dominant vascular disease characterized by mucocutaneous telangiectasias, epistaxis, GI bleeding and iron deficiency. Arteriovenous malformations also frequently occur in pulmonary, hepatic and cerebral circulation. The disease prevalence has been estimated between 1:5000 and 1:8000, but much higher rates are seen in geographically isolated regions such as Curacao and Bonaire (1:1330). At least 5 genetic mutations have been implicated in the development of HHT but the two major gene targets are endoglin (chromosome 9) and activin receptor like kinase 1, ALK 1 (chromosome 12). Endothelial cells derived from HHT patients express one half the normal levels of these proteins. In addition, increased plasma levels of vascular endothelial growth factor(VEGF) and TGF-Beta-1 have been noted in HHT patients. Inhibition of VEGF would appear to be an appropriate target to arrest the aberrant vascular proliferation in this disease. Despite better understanding of the pathophysiology of this syndrome, treatment advances have been hampered by the variability in clinical presentation and a lack of controlled clinical trials. Recommendations are largely based on anecdotal experience and case reports. We report a 77 year old patient with HHT (4/4 Curacao criteria) who developed a massive, prolonged transfusion requirement due to epistaxis and GI bleeding. Six units of packed red blood cells per week were required over a 4 year period to maintain a hemoglobin of 8 g/dl. He also required 400 mg of iron sucrose intravenously per week to maintain a ferritin level of 50ng/ml. Bone marrow biopsy demonstrated no evidence of a myelophthisic process or myelodysplastic syndrome. Erythropoietin levels were markedly elevated and coagulation studies were consistently normal. Bleeding persisted despite multiple endoscopies with extensive cauterization. He received sequential 3 month treatments with aminocaproic acid, sirolimus and thalidomide before receiving bevacizumab. Aminocaproic acid and sirolimus resulted in no change in the chronic 6 unit weekly transfusion requirement. Thalidomide transiently decreased the transfusion requirement to 4 units per week before being discontinued due to peripheral neuropathy. Bevacizumab at 5 mg/kg was administered every two weeks. By 4 weeks the transfusion requirement decreased to 1 unit per 2 weeks. By three months, he was transfusion independent and has remained so for three months. HHT is a vascular disorder with evidence of disordered angiogenesis. The clinical presentation and severity of symptoms varies widely. 3 case reports have previously demonstrated amelioration of bleeding due to bevacizumab. Our case is significant for the severity and prolonged duration of the bleeding. Local measures, aminocaproic acid and sirolimus failed to have any effect on the rate of bleeding in this patient. Thalidomide had a modest benefit at the expense of development of peripheral neuropathy. Bevacizumab completely corrected the prolonged and extreme bleeding in this case and it effectiveness was evident after the first dose. Our experience suggests that angiogenesis inhibition may have a significant role in the management HHT. Further investigation into patient selection, optimum dosing and duration of treatment is needed. Disclosures: Off Label Use: Bevacizumab is a monoclonal antibody to Vascular Endothelial Growth Factor. Our case describes its use to eliminate bleeding in a patient with Hereditary Hemorrhagic Telangiectasia.

scholarly journals Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4127
Author(s):  
Aline de Cristo Soares Alves ◽  
Franciele Aline Bruinsmann ◽  
Silvia Stanisçuaski Guterres ◽  
Adriana Raffin Pohlmann
Keyword(s):  
Monoclonal Antibody ◽  
Physicochemical Characterization ◽  
Vascular Endothelial ◽  
Organic Nanoparticles ◽  
Humanized Monoclonal Antibody ◽  
Angiogenesis Process ◽  
Endothelial Growth Factor ◽  
Drug Pharmacokinetics

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

scholarly journals Predictors of mortality in patients with hereditary hemorrhagic telangiectasia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
K. P. Thompson ◽  
◽  
J. Nelson ◽  
H. Kim ◽  
L. Pawlikowska ◽  
...  
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Cox Regression ◽  
Clinical Symptoms ◽  
Vascular Malformations ◽  
Smoking Status ◽  
Treatment Options ◽  
Gi Bleeding ◽  
Cox Regression Analysis ◽  
Predictors Of Mortality

Abstract Background Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark’s centre-treated HHT patients. However, clinical phenotypes vary widely in HHT, likely affecting mortality. We aimed to measure predictors of mortality among centre-treated HHT patients. HHT patients were recruited at 14 HHT centres of the Brain Vascular Malformation Consortium (BVMC) since 2010 and followed annually. Vital status, organ vascular malformations (VMs) and clinical symptoms data were collected at baseline and during follow-up (N = 1286). We tested whether organ VMs, HHT symptoms and HHT genes were associated with increased mortality using Cox regression analysis, adjusting for patient age, sex, and smoking status. Results 59 deaths occurred over average follow-up time of 3.4 years (max 8.6 years). A history of anemia was associated with increased mortality (HR = 2.93, 95% CI 1.37–6.26, p = 0.006), as were gastro-intestinal (GI) bleeding (HR = 2.63, 95% CI 1.46–4.74, p = 0.001), and symptomatic liver VMs (HR = 2.10, 95% CI 1.15–3.84, p = 0.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality (p > 0.05). Patients with SMAD4 mutation had significantly higher mortality (HR = 18.36, 95% CI 5.60–60.20, p < 0.001) compared to patients with ACVRL1 or ENG mutation, but this estimate is imprecise given the rarity of SMAD4 patients (n = 33, 4 deaths). Conclusions Chronic GI bleeding, anemia and symptomatic liver VMs are associated with increased mortality in HHT patients, independent of age, and in keeping with the limited treatment options for these aspects of HHT. Conversely, mortality does not appear to be associated with pulmonary AVMs or brain VMs, for which patients are routinely screened and treated preventatively at HHT Centres. This demonstrates the need for development of new therapies to treat chronic anemia, GI bleeding, and symptomatic liver VMs in order to reduce mortality among HHT patients.

scholarly journals Lactulose to the Rescue: A Case of Toxic Hepatic Encephalopathy Caused by Portosystemic Shunting and Epistaxis in a Patient with Hereditary Hemorrhagic Telangiectasia

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Ruchit N. Shah ◽  
Michael Makar ◽  
Nasir Akhtar ◽  
Erin Forster
Keyword(s):  
Hepatic Encephalopathy ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Rare Case ◽  
Autosomal Dominant ◽  
Rare Complication ◽  
Multiple Organ ◽  
Autosomal Dominant Disorder ◽  
Life Saving ◽  
Organ Systems ◽  
Portosystemic Shunting

Hereditary hemorrhagic telangiectasia (HHT) is an uncommon autosomal dominant disorder characterized by telangiectasias and arteriovenous malformations. Multiple organ systems are involved including the skin, lungs, gastrointestinal tract, and brain. Hepatic encephalopathy is an extremely rare complication of HHT and early diagnosis and treatment can be life-saving. We present a rare case of hepatic encephalopathy caused by HHT-induced portosystemic shunting treated with lactulose.

scholarly journals Future treatments for hereditary hemorrhagic telangiectasia

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Florian Robert ◽  
Agnès Desroches-Castan ◽  
Sabine Bailly ◽  
Sophie Dupuis-Girod ◽  
Jean-Jacques Feige
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Vascular Endothelial ◽  
Protein Receptor ◽  
Morphogenetic Protein ◽  
Receptor Like Kinase ◽  
Recent Developments ◽  
Frequent Mutations ◽  
Transcriptional Complex ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor

AbstractHereditary Hemorrhagic Telangiectasia (HHT), also known as Rendu-Osler syndrome, is a genetic vascular disorder affecting 1 in 5000–8000 individuals worldwide. This rare disease is characterized by various vascular defects including epistaxis, blood vessel dilations (telangiectasia) and arteriovenous malformations (AVM) in several organs. About 90% of the cases are associated with heterozygous mutations of ACVRL1 or ENG genes, that respectively encode a bone morphogenetic protein receptor (activin receptor-like kinase 1, ALK1) and a co-receptor named endoglin. Less frequent mutations found in the remaining 10% of patients also affect the gene SMAD4 which is part of the transcriptional complex directly activated by this pathway. Presently, the therapeutic treatments for HHT are intended to reduce the symptoms of the disease. However, recent progress has been made using drugs that target VEGF (vascular endothelial growth factor) and the angiogenic pathway with the use of bevacizumab (anti-VEGF antibody). Furthermore, several exciting high-throughput screenings and preclinical studies have identified new molecular targets directly related to the signaling pathways affected in the disease. These include FKBP12, PI3-kinase and angiopoietin-2. This review aims at reporting these recent developments that should soon allow a better care of HHT patients.

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