Table 6. [Treatment of Manifestations in Individuals with Hereditary Hemorrhagic Telangiectasia]. - GeneReviews®

Manifestation/ Concern	Treatment	Considerations/Other
Nosebleeds (epistaxis)	Humidification 2x-daily topical moisturizing therapy Hemostatic products (e.g., gauze, sponge, powder products)	Consider additional treatments if epistaxis is causing anemia or interfering w/normal activities.
Antifibrinolytic therapy (oral tranexamic acid) Ablation therapies (e.g., laser treatment, radiofrequency ablation, electrosurgery, sclerotherapy)	Consider if epistaxis does not respond to topical moisturizing therapies.
System antiangiogenic agents (e.g., intravenous bevacizumab) Septodermoplasty & nasal closure	Consider if epistaxis does not respond to topical moisturizing therapies, tranexamic acid, &/or ablative therapies [Faughnan et al 2020]. Surgical treatment for severe epistaxis in persons w/HHT should be performed by surgeons who regularly treat people w/HHT [Richer et al 2012].
GI bleeding	EGD is 1st-line diagnostic approach for suspected bleeding [Faughnan et al 2020]. Consider capsule endoscopy if EGD does not identify the source of suspected GI bleeding to help localize the source of bleeding [Grève et al 2010].	Endoscopic argon plasma coagulation may be administered concurrent w/initial EGD, but should be used sparingly during endoscopy & rpt sessions avoided [Faughnan et al 2020].
In those w/mild GI bleeding (i.e., anemia controlled w/iron replacement): consider oral antifibrinolytics (e.g., tranexamic acid).	Treatment is typically unnecessary unless iron therapy has been ineffective in maintaining a normal hemoglobin level.
In those w/GI bleeding that requires intravenous iron therapy or blood transfusions: consider systemic antiangiogenic agents (intravenous bevacizumab) [Faughnan et al 2020].
Anemia	Oral iron therapy IV iron in those intolerant or unresponsive to oral iron therapy Red blood cell transfusion only in those w/: hemodynamic instability/shock, comorbidities that require a higher hemoglobin target, need to ↑ the hemoglobin acutely (e.g., prior to surgery or pregnancy), or inability to maintain adequate hemoglobin despite frequent iron infusions
Pulmonary AVMs	Transcatheter embolotherapy is the treatment of choice: Consider occlusion for any pulmonary AVM w/a feeding vessel >1-2 mm in diameter [Trerotola & Pyeritz 2010]. Treatment is indicated for dyspnea, exercise intolerance, & hypoxemia, but is most important for prevention of lung hemorrhage & neurologic complications of brain abscess & stroke, even in those w/normal pulmonary function & oxygen saturation.	See Footnote 1. Occasionally, a small lesion cannot be reached by transcatheter embolotherapy because of its location or the size of the feeding vessel.
Chest CT &/or contrast echocardiography after embolization of pulmonary AVMs because of reported recanalization & development or growth of untreated pulmonary AVMs [Cottin et al 2007].	Usually, follow-up CT 6-12 mos post occlusion; then, if no recanalized or new pulmonary AVMs are noted, follow-up CT every 5 yrs [Trerotola & Pyeritz 2010, Faughnan et al 2011].
Cerebral abscess / Air embolism	If contrast echocardiography shows pulmonary shunting (even if no pulmonary AVM is identified on chest CT): Prophylactic antibiotics in accordance w/the American Heart Association protocol for dental cleaning & other procedures w/risk of bacteremia is advised because of the risk of abscess (esp brain abscess) assoc w/right-to-left shunting [Dupuis-Girod et al 2017]. Caution not to introduce air bubbles (to incl air filter if available) is recommended w/IV lines. Avoid scuba diving in those w/evidence of pulmonary AVMs.	Note: The risk assoc w/these lesions is not for subacute bacterial endocarditis.
Pulmonary artery hypertension	Treatment per cardiologist, pulmonologist, & other relevant specialists
Hepatic AVMs	Most w/symptomatic hepatic AVMs can be managed w/intensive medical therapy [Buscarini et al 2011]. Consider intravenous bevacizumab for those w/symptomatic high-output cardiac failure due to hepatic AVMs who have failed to respond to first-line management [Faughnan et al 2020].	See Footnote 1. Treatment of symptomatic hepatic AVMs is currently problematic. Embolization of hepatic AVMs (successful for treatment of pulmonary AVMs) has led to lethal hepatic infarctions.
Referral for consideration of liver transplantation for those w/symptomatic hepatic AVMs causing refractory high-output heart failure, biliary ischemia, or complicated portal hypertension [Faughnan et al 2020]	Liver transplantation has been standard treatment for those (usually older) persons whose symptoms of hepatic failure do not respond to medical management [Iyer et al 2019]. Liver biopsy should be avoided in persons w/HHT [Buscarini et al 2006].
Cerebral AVMs	Cerebral AVMs are typically treated using neurovascular surgery, embolotherapy, &/or stereotactic radiosurgery depending on size, location, & symptoms.	See Footnote 1.
*Intestinal polyps assoc w/SMAD4-HHT*	See Juvenile Polyposis Syndrome, Treatment of Manifestations.

Manifestation/
Concern

Treatment

Considerations/Other

Nosebleeds
(epistaxis)

Humidification
2x-daily topical moisturizing therapy
Hemostatic products (e.g., gauze, sponge, powder products)

Consider additional treatments if epistaxis is causing anemia or interfering w/normal activities.

Antifibrinolytic therapy (oral tranexamic acid)
Ablation therapies (e.g., laser treatment, radiofrequency ablation, electrosurgery, sclerotherapy)

Consider if epistaxis does not respond to topical moisturizing therapies.

System antiangiogenic agents (e.g., intravenous bevacizumab)
Septodermoplasty & nasal closure

Consider if epistaxis does not respond to topical moisturizing therapies, tranexamic acid, &/or ablative therapies [Faughnan et al 2020]. Surgical treatment for severe epistaxis in persons w/HHT should be performed by surgeons who regularly treat people w/HHT [Richer et al 2012].

GI bleeding

EGD is 1st-line diagnostic approach for suspected bleeding [Faughnan et al 2020].
Consider capsule endoscopy if EGD does not identify the source of suspected GI bleeding to help localize the source of bleeding [Grève et al 2010].

Endoscopic argon plasma coagulation may be administered concurrent w/initial EGD, but should be used sparingly during endoscopy & rpt sessions avoided [Faughnan et al 2020].

In those w/mild GI bleeding (i.e., anemia controlled w/iron replacement): consider oral antifibrinolytics (e.g., tranexamic acid).

Treatment is typically unnecessary unless iron therapy has been ineffective in maintaining a normal hemoglobin level.

In those w/GI bleeding that requires intravenous iron therapy or blood transfusions: consider systemic antiangiogenic agents (intravenous bevacizumab) [Faughnan et al 2020].

Anemia

Oral iron therapy
IV iron in those intolerant or unresponsive to oral iron therapy
Red blood cell transfusion only in those w/: hemodynamic instability/shock, comorbidities that require a higher hemoglobin target, need to ↑ the hemoglobin acutely (e.g., prior to surgery or pregnancy), or inability to maintain adequate hemoglobin despite frequent iron infusions

Pulmonary AVMs

Transcatheter embolotherapy is the treatment of choice:

Consider occlusion for any pulmonary AVM w/a feeding vessel >1-2 mm in diameter [Trerotola & Pyeritz 2010].
Treatment is indicated for dyspnea, exercise intolerance, & hypoxemia, but is most important for prevention of lung hemorrhage & neurologic complications of brain abscess & stroke, even in those w/normal pulmonary function & oxygen saturation.

See Footnote 1.
Occasionally, a small lesion cannot be reached by transcatheter embolotherapy because of its location or the size of the feeding vessel.

Chest CT &/or contrast echocardiography after embolization of pulmonary AVMs because of reported recanalization & development or growth of untreated pulmonary AVMs [Cottin et al 2007].

Usually, follow-up CT 6-12 mos post occlusion; then, if no recanalized or new pulmonary AVMs are noted, follow-up CT every 5 yrs [Trerotola & Pyeritz 2010, Faughnan et al 2011].

Cerebral abscess /
Air embolism

If contrast echocardiography shows pulmonary shunting (even if no pulmonary AVM is identified on chest CT):

Prophylactic antibiotics in accordance w/the American Heart Association protocol for dental cleaning & other procedures w/risk of bacteremia is advised because of the risk of abscess (esp brain abscess) assoc w/right-to-left shunting [Dupuis-Girod et al 2017].
Caution not to introduce air bubbles (to incl air filter if available) is recommended w/IV lines.
Avoid scuba diving in those w/evidence of pulmonary AVMs.

Note: The risk assoc w/these lesions is not for subacute bacterial endocarditis.

Pulmonary artery
hypertension

Treatment per cardiologist, pulmonologist, & other relevant specialists

Hepatic AVMs

Most w/symptomatic hepatic AVMs can be managed w/intensive medical therapy [Buscarini et al 2011].
Consider intravenous bevacizumab for those w/symptomatic high-output cardiac failure due to hepatic AVMs who have failed to respond to first-line management [Faughnan et al 2020].

See Footnote 1.
Treatment of symptomatic hepatic AVMs is currently problematic. Embolization of hepatic AVMs (successful for treatment of pulmonary AVMs) has led to lethal hepatic infarctions.

Referral for consideration of liver transplantation for those w/symptomatic hepatic AVMs causing refractory high-output heart failure, biliary ischemia, or complicated portal hypertension [Faughnan et al 2020]

Liver transplantation has been standard treatment for those (usually older) persons whose symptoms of hepatic failure do not respond to medical management [Iyer et al 2019].
Liver biopsy should be avoided in persons w/HHT [Buscarini et al 2006].

Cerebral AVMs

Cerebral AVMs are typically treated using neurovascular surgery, embolotherapy, &/or stereotactic radiosurgery depending on size, location, & symptoms.

See Footnote 1.

Intestinal polyps assoc w/SMAD4-HHT

See Juvenile Polyposis Syndrome, Treatment of Manifestations.

From: Hereditary Hemorrhagic Telangiectasia

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.