Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder characterized by development of high-flow arteriovenous malformations (AVMs) that can lead to stroke or high-output heart failure. HHT2 is caused by heterozygous mutations in ACVRL1, which encodes an endothelial cell bone morphogenetic protein (BMP) receptor, ALK1. BMP9 and BMP10 are established ALK1 ligands. However, the unique and overlapping roles of these ligands remain poorly understood. To define the physiologically relevant ALK1 ligand(s) required for vascular development and maintenance, we generated zebrafish harboring mutations in bmp9 and duplicate BMP10 paralogs, bmp10 and bmp10-like. bmp9 mutants survive to adulthood with no overt phenotype. In contrast, combined loss of bmp10 and bmp10-like results in embryonic lethal cranial AVMs indistinguishable from acvrl1 mutants. However, despite embryonic functional redundancy of bmp10 and bmp10-like, bmp10 encodes the only required Alk1 ligand in the juvenile-to-adult period. bmp10 mutants exhibit blood vessel abnormalities in anterior skin and liver, heart dysmorphology, and premature death, and vascular defects correlate with increased cardiac output. Together, our findings support a unique role for Bmp10 as a non-redundant Alk1 ligand required to maintain the post-embryonic vasculature and establish zebrafish bmp10 mutants as a model for AVM-associated high-output heart failure, which is an increasingly recognized complication of severe liver involvement in HHT2.
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PMID:BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance. 3182 46

Although Hereditary Hemorrhagic Telangiectasia (HHT) is characterized by an overwhelming bleeding propensity, patients with this disease may also present medical conditions that require antithrombotic therapy (AT). However, precise information on indications, dosage, duration, effectiveness, and safety of AT in HHT patients is lacking. We performed a retrospective analysis of the HHT Registry of our University Hospital and found 26 patients who received AT for a total of 30 courses (19 courses of anticoagulant therapy and 11 courses of antiplatelet therapy). Indications to treatments included: atrial fibrillation, venous thrombosis and pulmonary embolism, heart valve replacement, retinal artery occlusion, secondary prevention after either stroke or myocardial infarction, and thromboprophylaxis for surgery. The total time of exposure to antiplatelet therapy was 385 months and to anticoagulant therapy 169 months. AT was generally well tolerated, with no fatal bleedings and no significant changes in hemoglobin levels. However, we found three major bleedings, with an incidence rate of 6.5 per 100 patients per year. When only patients treated with anticoagulants were considered, the incidence rate of major bleedings increased to 21.6 per 100 patients per year. Our study indicates that major bleeding may occur in HHT patients receiving AT, with a substantially increased rate in those treated with anticoagulants. Further studies are needed to fully estimate the tolerability of antithrombotic drugs in HHT.
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PMID:Antithrombotic Therapy in Hereditary Hemorrhagic Telangiectasia: Real-World Data from the Gemelli Hospital HHT Registry. 3249 18

Hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu syndrome) is an inherited vascular disorder with a spectrum of clinical manifestations depending on lesion distribution. Epistaxis, mucocutaneous telangiectasia, and gastrointestinal bleeding are most common. Patients with pulmonary arteriovenous malformations are at serious risk of cerebral embolic stroke and abscess due to paradoxical embolism, indicating the need for early diagnosis and intervention. Herein, we report a 14-year-old boy who presented to his pediatrician's office with hypoxemia and personal history of epistaxis, family history of HHT, and radiologic workup demonstrating pulmonary and cerebral arteriovenous malformations. He was diagnosed with HHT and treated by endovascular embolization.
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PMID:Pulmonary arteriovenous malformation in a pediatric patient with epistaxis and hypoxemia. 3277 76

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the development of arteriovenous malformations. The arteriovenous shunts may result in high output heart failure, which predisposes to atrial dilatation and atrial fibrillation. Due to recurrent bleeding from epistaxis or the gastrointestinal tract, patients with HHT and atrial fibrillation are at high risk of bleeding if anticoagulated for stroke prevention. In this report, we present a case of a 74-year-old woman with a history of HHT and atrial fibrillation who developed a large left atrial thrombus that initially was thought to represent an atrial myxoma. The diagnosis was confirmed with cardiac magnetic resonance imaging, and the patient underwent surgical resection of the thrombus. This case demonstrates the role of different imaging modalities in the assessment of left atrial masses and presents an opportunity to review the data on safety of anticoagulation in patients with HHT.
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PMID:Left atrial thrombus mimicking myxoma in a patient with hereditary hemorrhagic telangiectasia: Diagnostic and therapeutic dilemmas. 3287 83


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