Antithrombotic therapy for atrial fibrillation in hereditary hemorrhagic telangiectasia

Virk, Zain M; Richardson, Tadarro L.; Al‐Samkari, Hanny

doi:10.1007/s11239-023-02839-1

Cited by 2 publications

(1 citation statement)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, antithrombotic therapy (anticoagulation and antiplatelet therapy) is widely used for HHT patients but is poorly tolerated, with objectively higher morbidity or worsened bleeding. This often leads to premature dose-reduction or the discontinuation of the therapy in some patients or treatment regimens [ 45 , 46 ]. Therefore, ENG-pathway genes could be used as the therapeutic targets for HHT1 [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

The ENG/VEGFα Pathway Is Likely Affected by a Nonsense Variant of Endoglin (ENG)/CD105, Causing Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) in a Chinese Family

Liu,

Fu,

Guo

et al. 2024

Genes

View full text Add to dashboard Cite

Hereditary hemorrhagic telangiectasia (HHT), also called Rendu–Osler syndrome, is a group of rare genetic diseases characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes. The correlations between the phenotype and genotype for HHT are not clear. An HHT Chinese pedigree was recruited. Whole exome sequencing (WES) analysis, Sanger verification, and co-segregation were conducted. Western blotting was performed for monitoring ENG/VEGFα signaling. As a result, a nonsense, heterozygous variant for ENG/CD105: c.G1169A:p. Trp390Ter of the proband with hereditary hemorrhagic telangiectasia type 1 (HHT1) was identified, which co-segregated with the disease in the M666 pedigree. Western blotting found that, compared with the normal levels associated with non-carrier family members, the ENG protein levels in the proband showed approximately a one-half decrease (47.4% decrease), while levels of the VEGFα protein, in the proband, showed approximately a one-quarter decrease (25.6% decrease), implying that ENG haploinsufficiency, displayed in the carrier of this variant, may affect VEGFα expression downregulation. Pearson and Spearman correlation analyses further supported TGFβ/ENG/VEGFα signaling, implying ENG regulation in the blood vessels. Thus, next-generation sequencing including WES should provide an accurate strategy for gene diagnosis, therapy, genetic counseling, and clinical management for rare genetic diseases including that in HHT1 patients.

show abstract

Section: Discussionmentioning

confidence: 99%

The ENG/VEGFα Pathway Is Likely Affected by a Nonsense Variant of Endoglin (ENG)/CD105, Causing Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) in a Chinese Family

Liu,

Fu,

Guo

et al. 2024

Genes

View full text Add to dashboard Cite

show abstract

How I treat bleeding in hereditary hemorrhagic telangiectasia

Al-Samkari

2024

Blood

View full text Add to dashboard Cite

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) affects 1 in 5,000 persons, making it the second most common inherited bleeding disorder worldwide. Telangiectatic bleeding, primarily causing recurrent epistaxis and chronic gastrointestinal bleeding, is the most common and most important manifestation of this multisystem vascular disorder. HHT-associated bleeding results in substantial psychosocial morbidity and iron deficiency anemia that may be severe. Although there remain no regulatory agency-approved therapies for HHT, multiple large studies, including randomized controlled trials, have demonstrated the safety and efficacy of antifibrinolytics for mild-to-moderate bleeding manifestations and systemic antiangiogenic drugs including pomalidomide and bevacizumab for moderate-to-severe bleeding. This has led to a recent paradigm shift away from repetitive temporizing procedural management towards effective systemic medical therapeutics to treat bleeding in HHT. In this article, 4 patient cases are used to illustrate the most common and most challenging presentations of HHT-associated bleeding that hematologists are likely to encounter in daily practice. Built on a framework of published data and supported by extensive clinical experience, guidance is given for modern evidence-based approaches to antifibrinolytic therapy, antiangiogenic therapy, and iron deficiency anemia management across the HHT disease severity spectrum.

show abstract

Antithrombotic therapy for atrial fibrillation in hereditary hemorrhagic telangiectasia

Cited by 2 publications

References 18 publications

The ENG/VEGFα Pathway Is Likely Affected by a Nonsense Variant of Endoglin (ENG)/CD105, Causing Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) in a Chinese Family

The ENG/VEGFα Pathway Is Likely Affected by a Nonsense Variant of Endoglin (ENG)/CD105, Causing Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) in a Chinese Family

How I treat bleeding in hereditary hemorrhagic telangiectasia

Contact Info

Product

Resources

About