(Familial hemorrhagic angiomatosis, Rendu-Osler disease, hereditary hemorrhagic telangiectasia)

Prevalence: 1/5,000 to 1/8000. Autosomal dominant transmission.

Different types have been identified:

-        type HHT1 [MIM 187 300]: ENG gene (9q33-34) coding for endoglin, 25 % of the cases.

-        type HHT2 [MIM 600 376]:  ACVLR1 or ALK1 gene (12q11-14) coding for a kinase of activin receptor, 70 % of the cases.

-        type HHT3 [MIM 601 101]: HHT3 gene (5q31)

-        type HHT4 [MIM 610 655]: gene on 7p14

-        type HHT5 [MIM 615 506]: GDF2 (10q11)

-        other mutations of the MADH4 gene (18q21.2) coding for the SMAD4 protein are associated with the combination of juvenile polyposis and Osler-Rendu disease [MIM 175 050].

The two main genes code for one of the receptors of the transforming growth factor β involved in cellular  proliferation and  strongly expressed in endothelial cells. This causes the formation of arteriovenous communications at the level of the skin, mucous membranes and many organs. The growth of the arteriovenous fistulae is influenced by hormonal changes that occur during adolescence, which explains the appearance or worsening of the symptoms from this period.

Clinical diagnosis criteria, known as Curaçao criterias: recurrent epistaxis, telangiectases, visceral arteriovenous malformations and familial history of a first degree relative with HHT.

Telangiectases (lower lip, cheekbones), aneurysms and arteriovenous malformations. Spontaneous and recurrent epistaxis: earlier onset in type I.

Arteriovenous malformations:

-         lung (48 %): often subclinical, poorly visible on chest X-ray: ultrasound with gas contrast allows their non-invasive screening. They can lead to: hemoptysis, cyanosis with orthodeoxia by shunt effect if the fistula is massive  (larger desaturation in the standing than in the supine position because the fistulae are usually located in the lung bases); stroke or brain abscess following paradoxical embolism which justifies their embolization. They are much more frequent in case of HHT type I (60 %) than in type II (20 %) and are as common in children as in adults. Their prevalence is estimated to 60 % in children. 60 % of the large fistulae are asymptomatic. A regular surveillance is recommended as those fistulae can appear or growth at any age. Treatment: embolization.

-         brain (10 %): headache, seizures, stroke, hemorrhage

-         spinal cord (< 1 %, but seem more frequent in children): pain, neurological disorders

-         gastrointestinal: stomach and duodenum (15 %), liver (30 %); hepatic vascular abnormalities are more common in type II; they cause mild cholestasis (sometimes necrosis), sometimes portal hypertension or porto-systemic encephalopathy; lesions of focal nodular hyperplasia

-         sometimes heart failure caused by arteriovenous fistulae.

-         pregnancy can aggravate pre-existing fistulae or cause new ones

Anesthetic implications: 

-         chronic anemia; order blood bank before any intervention at the level of vascular malformations (including at the level of the nasal cavity)

-         test for the presence of pulmonary arteriovenous malformations: measurement of SpO2 when breathing room air (orthodeoxia ?); ultrasound; check the absence of pulmonary arterial hypertension 

-         if possible, avoid any manoeuvre by nasal route (intubation, gastric tube): risk of catastrophic epistaxis. 

-         risk of hemoptysis.

-         check liver function. 

-         detailed medical history before planning a neuraxial block: risk of arteriovenous malformation that can be injured or decompensate following the modification of perimedullary pressures in case of spinal or epidural injection.

For the pregnant woman, the following decision tree is proposed:

1)          normal MRI before pregnancy : OK for perimedullary anesthesia

2)         no MRI before pregnancy: MRI without contrast during the 2nd or 3rd trimester

3)         in the presence of a lumbar arteriovenous malformation: contraindication to perimedullary anesthesia or analgesia

4)         in the presence of a cervical or dorsal arteriovenous malformation: evaluate the individual risk/benefit ratio of perimedullary anesthesia compared to general anesthesia

References : 

-        Radu C, Reich DL, Tamman R. 
Anesthetic considerations in a cardiac surgical patient with Osler- Weber-Rendu disease. 
       J Cardiothorac Vasc Anesth 1992; 6:461-4.

-        Lomax S, Edgcombe H.
       Anesthetic implications for the parturient with hereditary hemorrhagic telangiectasia.
       Can J Anaesth 2009; 56: 347-84.

-        Al-Saleh S, Dragulescu A, Manson D, Golding F, Traubici J, Mei-Zahav M, MacLusky IB, Faughnan ME, Carpenter S, Ratjen F. 
Utility of contrast echocardiography for pulmonary arteriovenous malformation screening in pediatric Hereditary Hemorrhagic Telangiectasia. 
J Pediatr 2012; 160: 1039-43.

-         Latino GA, Al-Saleh S, Alharbi N, Edwards C, Faughnan ME, Ratjen F. 
Prevalence of pulmonary arteriovenous malformations in children versus adults with hereditary hemorrhagic telengiectasia. 
J Pediatr 2013; 163: 282-4.

-        Weingarten TN, Hanson JW, Anusionwu KO, Moncrief ML et al. 
Management of patients with hereditary hemorrhagic telangiectasia undergoing general anesthesia : a cohort from a single academic center’s experience. 
J Anesth 2013 ; 27 : 705-11.

-         Pai V, Alexander A, Knecht K. 
The curious case of hypoxemia. 
Clin Pediatr 2014; 53: 300-2. 

-        Mowers KL, Sekarski L, White AJ, Grady RM.
Pulmonary arteriovenous malformations in children with hereditary hemorrhagic telangiectasia: a longitudinal study.
Pulm Circ 2018 ;8: doi 10.1177/2045894018786696

-        Poisson A, Vasdev A, Brunelle F, Plauchu H, Dupuis-Girod S.
Acute paraplegia due to spinal arteriovenous fistula in two patients with hereditary hemorrhagic telangiectasia.
Eur J Pediatr 2009; 168:135-9.

-        Crijnen TEM, van Gijlswijk S, De Dooy J, Voormolen MHJ et al.
A spinal arteriovenous fistula in a 3-year old boy.
Case Reports in Pediatrics 2014; doi 10.1155/2014/696703

-        Safi C, Troob S, Gudis DA.
Rapid sequence induction and intubation for patients with Hereditary Hemorrhagic Telangiectasia.
JAMA Otolaryngology-Head & Neck Surgery 2021; 147: 676-7

-        Nedunchezhian AS, Praceen R, Sethuraman M, Varma S.
Anesthetic challenges in a child with hereditary hemorrhagic telangiectasia with coexisting pulmonary and cerebral arteriovenous malformations for intracerebral hematoma evacuation: a case report.
J Clin Anesth 2021; 74:110430

-        Brady S, Tan T, O’Flaherty D.
Hereditary haemorrhagic telangiectasia and neuraxial anaesthesia in pregnancy: when should magnetic resonance imaging be performed ?
Anaesthesia Reports 2023, 11, e12227

Updated: May 2023