Integration of clinical parameters, genotype and epistaxis severity score to guide treatment for hereditary hemorrhagic telangiectasia associated bleeding

Joan D Beckman,Ofri Leitner,Karen L Smith,Raj S Kasthuri,Quefeng Li,Samuel T Hester

doi:10.1186/s13023-020-01453-1

Abstract

BackgroundHereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited disorder characterized by development of mucocutaneous telangiectases and visceral organ arteriovenous malformations, which can lead to recurrent, spontaneous bleeding and development of iron deficiency anemia. The primary objective of this study was to ascertain the relationship between epistaxis severity scores (ESS), laboratory values, genotype, and phenotype in HHT. Our secondary objective was to assess efficacy of systemic antifibrinolytic therapy in reducing ESS in HHT.MethodologyWe conducted a retrospective review of patients seen at the UNC HHT Center from January 1, 2009 to February 28, 2015. ESS, demographics, and results of genetic testing were abstracted from the medical record. Response to antifibrinolytic therapy was evaluated by comparing pre-post ESS.ResultsOne hundred and forty nine patients were eligible with 116 having genetic testing and 33 without. Age, hemoglobin and ferritin levels were predictive of ESS. Of the 116 patients that underwent genetic testing: 63 had an ACVRL1 mutation, 40 had an ENG mutation, 2 had a SMAD4 mutation, and 11 patients had no pathologic HHT genetic variation detected. Compared to patients without a detectable HHT-associated genetic variation, patients with a HHT-associated genetic variation had higher ESS scores (p < 0.05). Neither ESS nor genotype was predictive of pulmonary or brain AVMs. Twenty-four HHT patients with ESS > 4 were started on antifibrinolytic therapy (tranexamic acid or aminocaproic acid) and had a post-treatment ESS recorded. All patients had a decrease in ESS of > 0.71 (minimal meaningful difference), but patients taking antifibrinolytics displayed larger decreases. No patients on antifibrinolytics experienced a VTE with median follow up of 13 months.ConclusionsWe demonstrate that the ESS correlates with age, hemoglobin and ferritin. Additionally, we demonstrate that HHT patients with genetic mutations have higher ESS scores. Our data demonstrate that antifibrinolytics are effective in decreasing epistaxis severity and safe with long-term use in HHT patients.

Highlights

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited disorder characterized by development of mucocutaneous telangiectases and visceral organ arteriovenous malformations, which can lead to recurrent, spontaneous bleeding and development of iron deficiency anemia
Our data demonstrate that antifibrinolytics are effective in decreasing epistaxis severity and safe with long-term use in HHT patients
These data demonstrate that increased age, low Hgb and low ferritin are associated with more severe epistaxis

Summary

Introduction

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited disorder characterized by development of mucocutaneous telangiectases and visceral organ arteriovenous malformations, which can lead to recurrent, spontaneous bleeding and development of iron deficiency anemia. Affected individuals may develop visceral arteriovenous malformations (AVMs) in the brain, lung, or liver [1]. The diagnosis of HHT is made based on the Curacao criteria, which include: (i) spontaneous and recurrent epistaxis, (ii) mucocutaneous telangiectasias, (iii) family history of HHT in a first-degree relative, and (iv) visceral AVMs [2]. A pathogenic gene variant is expected to be identified in around 85% of patients with HHT, and genetic testing will be negative for such a mutation in about 15% of individuals with clinically diagnosed HHT [6, 7]

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