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Related Subjects: |Subarachnoid Haemorrhage |Upper Gastrointestinal Bleed (GI Bleed) |Epistaxis |Iron deficiency Anaemia |Haemolytic anaemia |Macrocytic anaemia |Megaloblastic anaemia |Microcytic anaemia |Myelodysplasia |Myelofibrosis

Introduction

• Hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease
• Rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation
• Telangiectasia found in the skin, mucous membranes
• Others found in the lungs, liver, and brain
• Most Cerebral AVMs in the HHT population are symptomatic.
• Family history of a parent, sibling or child with the same

The prevalence of brain AVMs in HHT patients was 10.4% in a large analysis of trials with no significant difference between males and females

Aetiology

• A disorder of angiogenesis with abnormal fragile blood vessels
• Mutations in several genes, including the ACVRL1, ENG, and SMAD4 genes
• HHT1 patients more likely to have brain AVMs than HHT2 patients.

Aetiology of stroke

• Bleeding from a cerebral vascular malformation
• Paradoxical embolism through a pulmonary AVM (rare)
• The vessels lack contractile elements and so given direct arterial connection, bleeding from telangiectases can be brisk and difficult to stop. This may be seen with GI Bleeds.

Most individuals with a PAVM(s) have Hereditary haemorrhagic telangiectasia

Clinical

• Difficulties with Epistaxis seen in most by adulthood
• GI bleeding, Haematemesis, Melaena, Fe deficiency anaemia often over age of 50
• Haemorrhagic stroke as risk of AVMS
• Mucocutaneous lesions in skin and oral cavity and nose
• Embolic stroke via paradoxical embolism via pulmonary AVM
• Pulmonary AVM can rupture, leading to haemoptysis

Clinical Signs

Types

• Type 1: mutations in the ENG gene. Brain AVMS in 13.4 %
• Type 2: mutations in the ACVRL1 gene. Brain AVMS in 2.4 %
• Juvenile polyposis/hereditary haemorrhagic telangiectasia syndrome is caused by mutations in the SMAD4 gene.

Differential

• Vasculitis rash
• Thrombocytopenia
• Telangiectasis of chronic liver disease are spider like with a central core and small vessels radiating outward

Diagnostic clinical criteria

Investigations

• FBC: exclude Fe deficiency anaemia from GI blood loss.
• Ferritin and Iron studies as well as ESR, CRP, U&E, LFTs, B12,folate
• Stroke presentation: Brain Imaging - CT/MRI/MRA
• CXR or Lung CT: may show lung lesion - AVM
• Cerebral Angiography if AVM suspected. The Spetzler-Martin grade for HHT related lesions is 2 or less in nearly 90% of patients.
• Bubble echo shown to be a sensitive screen for Pulmonary AVMs which can lead to paradoxical emboli. CT Pulmonary angiogram if positive bubble echo. This avoids radiation in young adults. This may need to be repeated at 5-year intervals.
• Colonoscopy and upper endoscopy +/- capsule endoscopy. Those with mutations in the SMAD4 gene may be at increased risk for polyps. Alternatively, may be done to exclude other cause of Fe deficiency anaemia
• Molecular genetic testing is used to establish the genetic subtype of hereditary haemorrhagic telangiectasia in a clinically affected individual and family, and for early diagnosis to allow for appropriate screening and preventive treatment.

Management

• ABC, Stroke management for Haemorrhagic stroke. See Topic
• Acute management for Upper GI Bleed as needed. Transfusion if needed. See Topic
• ENT referral for epistaxis - Laser ablation is usually recommended as the intervention for control of mild to moderate nosebleeds
• Gastroenterology review for GI bleeds. Iron replacement therapy for anaemia.
• Avoid antithrombotic drugs. Antifibrinolytic drugs such as tranexamic acid have been used in select patients
• Genetic counselling.
• Management of Cerebral Arteriovenous Malformations if found. A recent study has found that functional outcomes were not statistically different between those who had surgery and those who didn't on long term follow-up. Link
• Closure of Pulmonary AVM if embolic stroke by Interventional neuroradiology if needed. Any PAVM with a feeding artery > 1–3 mm detected by chest CT should be considered for treatment by transcatheter embolization.

References

• Prevalence and characteristics of brain arteriovenous malformations in hereditary haemorrhagic telangiectasia: a systematic review and meta-analysis. J Neurosurg. 2017 Aug;127(2):302-310.
• MR of hereditary haemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations.
• Surgical Treatment vs Nonsurgical Treatment for Brain Arteriovenous Malformations in Patients with Hereditary Haemorrhagic Telangiectasia: A Retrospective Multicentre Consortium Study.
• Hereditary haemorrhagic telangiectasia: An overview of diagnosis, management, and pathogenesis Genetics in Medicine volume 13, pages 607–616 (2011)