Gastrointestinal Bleeding in Patients with Hereditary Hemorrhagic Telangiectasia: Risk Factors and Endoscopic Findings

Mora-Luján, José María; Iriarte, Adriana; Alba, Esther; Sánchez-Corral, Miguel Ángel; Berrozpe, Ana; Cerdà, Pau; Cruellas, Francesc; Ribas, J.; Castellote, José; Riera‐Mestre, Antoni

doi:10.3390/jcm9010082

Cited by 24 publications

(19 citation statements)

References 43 publications

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“…Canzonieri et al and van Tuyl et al systemically studied the extent of GI involvement with gastroscopy, video capsule endoscopy, and colonoscopy in 22 and 35 HHT patients, respectively, and found a higher prevalence of telangiectasia in patients with ENG mutation [8,35,36]. In a recent study, Mora-Luján et al reported that age, tobacco use, ENG mutation, and hemoglobin levels were associated with GI involvement in HHT comparing 67 patients with GI disease and 28 with negative GI study [37]. However, Berg et al, Sabbà et al and Letteboer et al assessing genotype-phenotype relationship in HHT patients, reported a similar incidence of GI telangiectasia in HHT1 and HHT2 patients [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry

Sánchez-Martínez

Iriarte

Mora-Luján

et al. 2020

Orphanet J Rare Dis

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Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease with autosomal dominant inheritance. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in more than 90% of cases submitted to molecular diagnosis. Methods: We used data from the RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry to describe genetic variants and to assess their genotype-phenotype correlation among HHT patients in Spain. Results: By May 2019, 215 patients were included in the RiHHTa registry with a mean age of 52.5 ± 16.5 years and 136 (63.3%) were women. Definitive HHT diagnosis defined by the Curaçao criteria were met by 172 (80%) patients. Among 113 patients with genetic test, 77 (68.1%) showed a genetic variant in ACVRL1 and 36 (31.8%) in ENG gene. The identified genetic variants in ACVRL1 and ENG genes and their clinical significance are provided. ACVRL1 mutations were more frequently nonsense (50%) while ENG mutations were more frequently, frameshift (39.1%). ENG patients were significantly younger at diagnosis (36.9 vs 45.7 years) and had pulmonary arteriovenous malformations (AVMs) (71.4% vs 24.4%) and cerebral AVMs (17.6% vs 2%) more often than patients with ACVRL1 variants. Patients with ACVRL1 variants had a higher cardiac index (2.62 vs 3.46), higher levels of hepatic functional blood tests, and anemia (28.5% vs 56.7%) more often than ENG patients. Conclusions: ACVRL1 variants are more frequent than ENG in Spain. ACVRL1 patients developed symptomatic liver disease and anemia more often than ENG patients. Compared to ACVRL1, those with ENG variants are younger at diagnosis and show pulmonary and cerebral AVMs more frequently.

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Section: Discussionmentioning

confidence: 99%

Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry

Sánchez-Martínez

Iriarte

Mora-Luján

et al. 2020

Orphanet J Rare Dis

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“…In fact, Plauchu et al reported that only 1.5% of patients had GI bleeding at ages younger than 30 [28]. In adults, anemia is a typical complication of chronic GI bleeding in HHT [6,[36][37][38], and Kasthuri et al described GI bleeding as an independent predictor of anemia in adult HHT patients [12]. Given the typically later-life onset of GI bleeding, the current HHT guidelines [6] recommend monitoring hemoglobin and hematocrit after the age of 35, as a marker of GI bleeding.…”

Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Correlations in Children with HHT

Kilian

Latino

White

et al. 2020

JCM

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Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype–phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype–phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0–18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presence of a combined phenotype—defined as both pulmonary AVMs and brain VMs—was also associated with ENG mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with SMAD4 genotype (p < 0.001). We conclude that genotype–phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with ENG mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.

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“…The association between genotype, epistaxis, and visceral AVMs has been previously evaluated [6,13,14,[29][30][31][32]. Epistaxis is the most common (> 90%) manifestation in patients with both ENG and ACVRL1 mutations, although patients with ENG mutations are believed to have onset of epistaxis at a younger age [6,[13][14][15]33].…”

Section: Discussionmentioning

confidence: 99%

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

Beckman

Hester

et al. 2020

Orphanet J Rare Dis

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Background: 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. 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. Methodology: We 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. Results: One 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 HHTassociated 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. Conclusions: We 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.

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Gastrointestinal Bleeding in Patients with Hereditary Hemorrhagic Telangiectasia: Risk Factors and Endoscopic Findings

Cited by 24 publications

References 43 publications

Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry

Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry

Genotype–Phenotype Correlations in Children with HHT

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

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