Hereditary hemorrhagic telangiectasia and the anesthesiologist

Sandeep Kumar Kar1, Tanmoy Ganguly2,

1Assistant Professor; 2PDT
Department of Cardiac Anesthesiology, Institute of Postgraduate Medical Education & Research, Kolkata (India)
 Correspondence:  Dr Sandeep Kumar Kar, Department of Cardiac Anesthesiology, Institute of Postgraduate Medical Education & Research, Kolkata (India); E-mail: sndpkar@yahoo.co.in
ABSTRACT
Osler-Weber-Rendu disease (OWRD) or Hereditary Hemorrhagic Telangiectasia (HHT) is a rare autosomal dominant disorder that causes muco-cutanesous and visceral vascular dysplasia and results in increased tendency for bleeding. Patients with HHT presenting with continuous bleeding pose a serious problem to the Anesthesiologist .Pre-existing anemia due to recurrent bleeding is common and sudden decompensation may lead to heart failure. Uncontrolled bleeding may occur from skin lesions during patient positioning and transport. Epistaxis may lead to aspiration of blood into trachea causing pulmonary edema. Intravenous access may be difficult. Sudden change in blood pressure may cause bleeding from arteriovenous malformations (AVMs) anywhere in the body, most serious of which is from cerebral AVM. Gastric distension may occur from ingested blood and may cause reflux and aspiration during induction. Any instrumentation including laryngoscopy and intubation, nasogastric tube insertion, urinary catheterization should be carried out with utmost caution as bleeding may occur from undetected lesions. Management include blood transfusion, antifibrinolytics and surgical hemostasis. Anesthesia strategy should include rapid sequence induction and controlled hypotension.

Key words: Telangiectasia, Hereditary Hemorrhagic; Osler-Rendu Disease; Osler-Weber-Rendu Syndrome; Congenital Abnormalities; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformation

Citation: Kar SK, Ganguly T. Hereditary hemorrhagic telangiectasia and the anesthesiologist. Anaesth Pain & Intensive Care 2017;21(3): 387-392

Received – 5 Mar 2017; Reviewed & Accepted – 16 Mar 2017

INTRODUCTION
Osler-Weber-Rendu disease (OWRD) or Hereditary Hemorrhagic Telangiectasia (HHT) is a rare autosomal dominant disorder that causes muco-cutanesous and visceral vascular dysplasia and results in increased tendency for bleeding.1-4 Patients with HHT may present with variety of symptoms and management differs accordingly. Epistaxis is the most common symptom of HHT and mucocutaneous telangiectasia is the most common sign.5
23fig1

Figure 1: Endoscopic view of the angiofibroma
INCIDENCE
HHT is a rare systemic fibro vascular dysplasia6 with incidence varying from 1 in 5,000 to 10,0007 to 1 to 2 in 1,00,0006. Sutton8 in 1864 first described this syndrome in a man with a vascular malformation and recurrent epistaxis. In 1896 Rendu9 first noted the association between hereditary epistaxis and telangiectasia in a 52 years old man. Osler10 in 1901 and Weber11 in 1907 further elaborated the association between hemorrhagic lesions in skin and mucous membranes and its familial inheritance. Although the disease is popularly known as Osler-Weber-Rendu syndrome, the name ‘hereditary hemorrhagic telangiectasia’ suggested by Hanes12 in 1909, recognizes the characteristics that define the disease.

GENETICS OF HHT
HHT is manifested by mucocutaneous telangiectasias and arteriovenous malformations (AVMs) in different parts of body. Lesions can affect the nasopharynx, central nervous system (CNS), lung, liver, and spleen, as well as the urinary tract, gastrointestinal (GI) tract, conjunctiva, trunk, arms, and fingers.2,13 Impaired signaling of transforming growth factor-ß/bone morphogenesis protein (TGF-β/BMP)14-17 as well as vascular endothelial growth factor (VEGF)18,19 has been attributed as the primary cause of HHT. The gene mutations found to be responsible are as follows in Table 1.

 

Table 1: Types of HHT with genetic basis
HHT types Mutated genes Gene location
HHT1 ENG20 Long arm of chromosome 921-23
HHT2 ALK1 (Activin receptor-like kinase 1),  also  called ACVRL124,25 Long arm of chromosome 12
hereditary benign telangiectasia (HBT), HHT3 RASA1 26 chromosome 5q14
HHT4 Chromosome 7p1427
HHT + Juvenile polyposis coli SMAD4/MADH428-30 18q21.2
HHT2 + primary pulmonary hypertension BMPRII31,32 2q33
DIAGNOSIS
The diagnosis of HHT is made clinically on the basis of the Curaçao criteria3, established in June 1999 by the Scientific Advisory Board of the HHT Foundation International, Inc. (Table 2), and recommended by HHT Foundation International - Guidelines Working Group,33 or by identification of a causative mutation.

Table 2: Curaçao criteria
Criterion Description
Epistaxis Spontaneous and recurrent
Telangiectasias Multiple, at characteristic sites: lips, oral cavity, fingers, nose
Visceral lesions GI Telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs
Family history A first degree relative with HHT according to these criteria
“definite” if 3 or more criteria are present, “possible or suspected” if 2 criteria are present, and “unlikely” if 0 or 1 criterion is present.
Histopathology of HHT lesions show many layers of smooth muscle cells without elastic fibers and very frequently arterioles directly communicating with smooth muscle cells. As a result telangiectasias are very sensitive to slight trauma and friction. HHT may present in children as bleeding but usual age of presentation in adulthood.4 Male and females are equally affected.34 Classic triad of presentation include telangiectasias of the skin and mucous membranes, epistaxis, and a positive family history. Epistaxis may be present in upto 95% cases,4,35 whereas skin lesions account for 75-90% of presentations.35,36 Skin telangiectasias rarely cause bleeding4. Gastrointestinal telangiectasia may occur in 10-33% patients37 most commonly in the stomach and upper duodenum.37 Significant bleeding from gastrointestinal tract may occur in 25% patients older than 60 years and may increase with age.38 Pulmonary involvement in the form of arteriovenous malformations (AVMs) may be present in 75% HHT1 and 44% HHT2 patients.39 Patients with pulmonary involvement are at high risk of developing cerebral thrombotic and embolic events including stroke, brain abscess, or transient ischemic attacks due to right-to-left shunting.14,37   Cerebral AVMs may be present 15-20% HHT1 and 1-2% HHT2 patients,39-43 and may present with seizure, headache or intracranial haemorrhages.4,44 Hepatic AVMs may be present upto 74% cases45 but usually asymptomatic4.

MANAGEMENT
Management strategies for AVMs associated with HHT may differ with location and presentation and depicted in Table 3.

Table 3: Management strategy of HHT according to site of involvement
Location Lesions Indications of management Management
Nose Telangiectasia, AVMs Recurrent epistaxis Sclerotherapy with sodium tetradecyl sulphate46, submucosal radiofrequency47, Bevacizumab48, Septal mucosal dermoplasty39,49, Embolization of external carotid artery branches50,
Skin Telangiectasia Pain2, cosmesis4 Cauterization, hypertonic saline sclerotherapy, dye laser treatment51. Pulsed Nd:YAG laser52,
Gastro intestinal tracts AVMs, Angio-dysplasia4 Chronic anemia, melena Diagnosis: Endoscopy, Angiography4
Management: Bipolar electrocoagulation4, Laser4, estrogen-progesterone therapy53, interferon α54
Lungs AVMs Exercise intolerance, cyanosis, migraine headaches, polycythemia and clubbing

CNS events14,40
During pregnancy55		 Feeder vessel >3 mm: Transcatheter embolisation56,

Smaller lesion: Follow up14
Antibiotic prophylaxis to prevent brain abscess
Diffuse pulmonary AVM Severe hypoxia Lung transplantation4
CNS Cerebral and spinal AVMs Transcatheter embolization, resection, stereotactic radiosurgery57,58
Liver AVMs, Life threatening portosystemic shunts Liver transplant59-61
Bevacizumab62
Patients with HHT presenting with continuous bleeding pose a serious problem to the Anesthesiologist .Pre-existing anemia due to recurrent bleeding is common and sudden decompensation may lead to heart failure. Uncontrolled bleeding may occur from skin lesions during patient positioning and transport. Epistaxis may lead to aspiration of blood into trachea causing pulmonary edema. Intravenous access may be difficult. Sudden change in blood pressure may cause bleeding from AVMs anywhere in the body, most serious of which is from cerebral AVM. Gastric distension may occur from ingested blood and may cause reflux and aspiration during induction. Any instrumentation including laryngoscopy and intubation, nasogastric tube insertion, urinary catheterization should be carried out with utmost caution as bleeding may occur from undetected lesions.

Box 1: Perioperative management problems in HHT patient

Perioperative management risk and problems
  1. Patient may present with:
  • Preexisting anemia
  • AVMs elsewhere
  • Blood in stomach
  • Aspiration
  1. Surgery related:
  • Difficult exposure
  • Difficult hemostasis
  • Prolonged surgery
  1. Problems in anesthesia conduct:
  • Positioning and transport
  • Perioperative aspiration risk
  • Unstable hemodynamics
  • IV access
  • Instrumentation
  • Massive blood transfusion
 
 

In hemodynamically stable patients, posted for elective surgery, preoperative optimization of the anemic status is corrected with oral or parenteral iron and if necessary erythropoiesis-stimulating agent63. Preoperatively angiogenesis inhibitors or hormone therapy should be considered in selected patients to reduce perioperative bleeding. Careful history and physical examination may indicate any systemic involvement and standard radiological imaging with angiography may be performed to search for hemangiomas in brain, lung, gastrointestinal tract, nose and paranasal sinuses.  In unstable patient presenting with severe bleeding focus should be directed to simultaneous resuscitation and hemostasis. Blood transfusion forms the mainstay of volume resuscitation in severely volume depleted patient. Epistaxis should be controlled with tight nasal packing immediately followed by cauterization of bleeding vessels and Septodermoplasty if required. Since bleeding does not result from a defect in coagulation cascade, but from the malformed vascular structures, platelet or plasma transfusions are of no use and reserved only to supplement the loss. Antifibrinolytics including tranexamic acid64,65 and aminocaproic acid66 have been used with success to control epistaxis. In addition to antifibrinolytic effects, tranexamic acid also stimulates the expression of ALK-1 and endoglin, as well as the activity of the ALK-1/endoglin pathway.67 Intraoperatively controlled hypotension should be achieved with nitroglycerine or inhaled anesthetics or alpha 2 agonists to reduce bleeding.

Conclusion
Patients with Osler-Weber-Rendu disease (OWRD) or Hereditary Hemorrhagic Telangiectasia (HHT) may present with uncontrolled bleeding. Resuscitation along with hemostasis forms the cornerstone of treatment. As the bleeding occurs from malformed vessels, standard coagulation tests will reveal no abnormality. Management strategies include blood transfusion, antifibrinolytics and surgical hemostasis. Anesthesia planning should include rapid sequence induction and controlled hypotension.

Conflict of interest: None declared by the authors
Authors’ Contribution:
SKK: Concept and writing

TG: Contributing author

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