Hereditary hemorrhagic telangiectasia and pregnancy: potential adverse events and pregnancy outcomes

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant condition with a prevalence of ~1 in 5,000 individuals. The pathophysiology of this condition centers on the lack of capillary beds between arterioles and venules, leading to direct contact between these vessels. This results in telangiectases on characteristic locations such as the face, fingers, mouth, and nasal mucosa. Visceral arteriovenous malformations (AVMs) are also observed in many patients, and these are most commonly seen in the brain, gastrointestinal tract, and lungs. Liver AVMs are present in many patients with HHT, though these individuals are usually asymptomatic; however, liver AVMs may lead to serious complications, such as high output cardiac failure. Diagnosis of HHT hinges upon fulfilling three out of four criteria: family history of the condition, mucocutaneous telangiectases, spontaneous and recurrent episodes of epistaxis, and visceral AVMs. Management is guided by international consensus guidelines and targets patients’ specific AVMs. Prognosis is good, though severe complications including hemorrhage and paradoxical emboli are possible. Novel therapeutics are being explored in clinical trials; bevacizumab and pazopanib inhibit angiogenesis, while thalidomide bolsters blood vessel maturation. Pregnancy in patients with HHT is considered high risk. While the majority of pregnancies proceed normally, severe complications have been reported in some women with HHT; these include heart failure, intracranial hemorrhage, pulmonary hemorrhage, and stroke. Such complications occur most often in the second and third trimesters when maternal changes such as peripheral vasodilation and increased cardiac output are at their maximum. Awareness of the diagnosis of HHT has been associated with improved outcomes in pregnancy. Management guidelines for pregnant patients with HHT are reviewed.

TGF-β signaling promotes tumor vasculature by enhancing the pericyte-endothelium association

“…Telangiectases consist of abnormally dilated thin-walled vessels that are prone to spontaneous and recurrent bleeding. HHT is the autosomal-dominant trait and about 90% of HHT cases are linked to genetic inactivation of the TGF-β pathway in endothelial cells [ 43 , 44 ]. Recent studies have linked the pathogenesis of HHT to excessive angiogenesis and loss of capillary bed between arteries and veins [ 45 ].…”

A Case Report of Transient Exertional Hypoxemia in Pregnancy and Review of Hereditary Hemorrhagic Telangiectasia

“…Also known as Osler-Weber-Rendu syndrome, this autosomal dominant disease affects 1 in 5,000 people [3]. The mutations in patients with HHT produce abnormal TGF-β proteins that cause an inability to properly recruit smooth muscle cells during angiogenesis leading to AVMs [4]. A common diagnostic criterion used to identify patients with HHT is the Curacao criteria.…”

“…This decision was supported in a systematic review by Lomax et al which demonstrated that 53% (9/17) of patients with HHT (with predominantly pulmonary AVMs) were delivered by cesarean section although the indications for cesarean delivery as well as previous delivery history are unclear. Two of these patients are also noted to deliver with forceps assistance, although the indication for this choice is not specified [4].…”

Diagnostik und Behandlung der hereditären hämorrhagischen Teleangiektasie

“…Meist ist es zumal so, dass die Diagnosestellung erst nach Abschluss der Familienplanung erfolgt [50]. Treten Komplikationen auf, so ist dies gehäuft im zweiten und dritten Trimenon der Fall, da in dieser Zeit der periphere Gefäßwiderstand abnimmt und gleichzeitig das Herzzeitvolumen um bis zu 50 % ansteigt, was zu einer Exazerbation der vorhandenen Shuntverbindungen führen kann [51]. Die Aufgabe des behandelnden Arztes ist es, Patienten über die Wichtigkeit von Organuntersuchungen vor Beginn der Schwangerschaft aufzuklären, um eventuell lebensbedrohlichen Komplikationen vorbeugen zu können [50].…”