eMedicine Specialties > Pediatrics: General Medicine > Hematology

Osler-Weber-Rendu Syndrome: Treatment & Medication

Author: Lawrence C Wolfe, MD, Senior Associate in Pediatric Hematology/Oncology, Schneider Children's Hospital
Coauthor(s): Arun Panigrahi, MD, Resident Physician, Department of Pediatrics, Tufts University School of Medicine
Contributor Information and Disclosures

Updated: Nov 20, 2009

Treatment

Medical Care

  • Medical and surgical care in patients with Osler-Weber-Rendu syndrome are aimed at decreasing the amount of hemorrhage and minimizing the sequelae of arteriovenous malformations (AVMs), which may develop in multiple organ systems. Historically, estrogen-related hormones and antifibrinolytic agents have been used the management of bleeding; however, recent studies reveal that their use likely increases the risk of thrombotic events in patients with Osler-Weber-Rendu who have pulmonary AVMs. Because of this finding, patients should receive screening studies for the presence of pulmonary AVMs prior to treatment of the disease.
  • Novel therapies, such as N-acetylcysteine and tamoxifen (antiestrogenic agent), are also being studied as options for management of recurrent epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT).9,10 A recent case report also illustrates the use of bevacizumab (Avastin) in the treatment of HHT.11
  • Recent recommendations also advocate the use of antibiotic prophylaxis prior to surgical or dental procedures in all patients with known pulmonary AVMs or positive contrast echocardiography findings (agitated saline solution transthoracic contrast echocardiography [TTCE] grade 1 or higher). Recent studies also recommend that women with HHT who conceive should be considered to have high-risk pregnancies because of rare major complications and improved survival outcome following prior recognition.12

Surgical Care

  • Septal dermoplasty can reduce the severity of epistaxis by 75%. This procedure is performed by replacing the nasal mucosa with autologous skin grafts. Telangiectasias may also develop on the autologous skin grafts.
  • Pulsed dye laser treatment may also be used to photocoagulate telangiectasias in the nasal mucosa. As many as 3 subsequent treatments may be necessary before any change in bleeding frequency or severity is observed.
  • Endovascular embolization for treatment of severe acute epistaxis is also a treatment modality.13 Patients who undergo endovascular embolization often require repeat embolization and surgical procedures.
  • Septectomy combined with septal dermoplasty may also be a viable option for patients with severe transfusion-dependent epistaxis.14
  • Embolization of pulmonary AVMs has been shown to be a safe and effective procedure that prevents brain abscess and ischemic stroke if complete occlusion of all pulmonary AVMs is acheived.15 Embolization is currently recommended for every pulmonary AVM with a feeding artery of 3 mm or more.3 Other treatment modalities for pulmonary AVMs include surgical ligation.
  • Life-threatening GI bleeds are often effectively treated by segmental bowel resection.
  • Embolization of the hepatic artery in selected patients with liver involvement may be used, as well as liver transplantation.16,17
  • Radiosurgery, microsurgery, or embolization are used to treat cerebral AVMs.

Consultations

Consultation with multiple specialists may be useful in the diagnosis and treatment of this disease. Certain specialists may only warrant consultation when certain complications arise.

  • Dermatologist
  • Pulmonologist
  • Hematologist
  • Gastroenterologist
  • Neurologist and neurosurgeon

Diet

  • In most patients, no special diet is required.
  • Iron can be depleted if the patient experiences chronic blood loss.
  • Folate requirements can be high if the bone marrow is chronically activated.

Activity

  • Most patients can continue normal activities.

Medication

Estrogen and progesterone combinations and aminocaproic acid may help safely control mucosal bleeding in patients with Osler-Weber-Rendu syndrome whose screening test findings reveal the absence of pulmonary arteriovenous malformations (AVMs).

Oral contraceptives

These agents may be used to decrease the amount of bleeding. Topical preparations can be used to help strengthen mucosa and decrease the susceptibility of the mucosa to external trauma. Prior to use, screening tests for pulmonary AVMs should be performed because of the risk of complications involving thromboembolism.


Norethindrone acetate and ethinyl estradiol (Yasmin, Loestrin 1.5/30)

Used to decrease mucosal bleeding. Probably works by strengthening mucosal tissues and thereby making them more resistant to trauma.

Adult

PO contraceptives that contain ethinyl estradiol 30 mcg and norethindrone 1.5 mg/tab: 1 tab PO qd
Use until bleeding controlled

Pediatric

Not well established; use adult doses for older children

May reduce hypoprothrombinemic effects of anticoagulants; estrogen levels may be reduced with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; an increase in corticosteroid levels may occur when administered concurrently with ethinyl estradiol; use of ethinyl estradiol with hydantoins may cause spotting, breakthrough bleeding, and pregnancy; increase in fluid retention caused by estrogen intake may reduce seizure control

Documented hypersensitivity; thrombophlebitis or thromboembolic disorders; history of stroke; coronary artery disease; active liver disease; carcinoma of the breast; undiagnosed vaginal bleeding; ophthalmic vascular disease; pregnancy

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Women >35 y who smoke are at increased risk of serious adverse effects on the heart and blood vessels; caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease

Antifibrinolytics

These agents are used to enhance hemostasis when fibrinolysis contributes to bleeding. Prior to use, screening for pulmonary AVMs should be performed due to risk of thromboembolic events.


Aminocaproic acid (Amicar)

Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. Used to prevent or treat mucosal bleeding caused by bleeding disorders or trauma.

Adult

3.5 g IV initially, then 1 g/h until bleeding stops; not to exceed 8 h treatment duration
3.5 g/dose PO tid/qid for 3-4 d
Topical: Insert a gauze soaked in a 10% solution of aminocaproic acid into the nasal cavity

Pediatric

50-100 mg/kg IV infused over 30-60 min, then 30-50 mg/kg/h until bleeding stops; not to exceed 8 h treatment duration
50 mg/kg/dose PO tid/qid for 3-4 d
Topical: Administer as in adults

Coadministration with estrogens may cause increase in clotting factors, leading to a hypercoagulable state

Documented hypersensitivity; evidence of active intravascular clotting process; disseminated intravascular coagulation ([DIC] because aminocaproic acid can be fatal in patients with DIC, differentiate between hyperfibrinolysis and DIC)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Reduce dose in cardiac, renal, or hepatic disease

Immunomodulating agent

Two case reports have documented the regression of Osler-Weber-Rendu lesions with the use of interferon alpha in patients who were treated for other indications.18,19


Interferon alfa-2a (Roferon-A)

Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.

Adult

HHT: Not established
Airway hemangiomas: 3 million IU/m2/d SC

Pediatric

HHT: Not established
Airway hemangiomas: Administer as in adults

Theophylline may increase toxicity of interferon alpha by reducing clearance; cimetidine may increase antitumor effects of interferon alpha; zidovudine and vinblastine may increase toxicity of interferon alpha

Documented hypersensitivity; avoid in patients who have anaphylactic sensitivity to mouse IgG, egg protein, or neomycin; autoimmune hepatitis

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Depression and suicidal ideation may be side effects of treatment; infrequently, severe or fatal GI hemorrhage has been reported in association with interferon alpha therapy
Bone marrow suppression: Prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cell, and bone marrow hairy cells; monitor patient periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 6 mo, discontinue treatment; if response occurs, continue treatment until no further improvement observed (not known whether continued treatment after that time is beneficial)

More on Osler-Weber-Rendu Syndrome

Overview: Osler-Weber-Rendu Syndrome
Differential Diagnoses & Workup: Osler-Weber-Rendu Syndrome
Treatment & Medication: Osler-Weber-Rendu Syndrome
Follow-up: Osler-Weber-Rendu Syndrome
Multimedia: Osler-Weber-Rendu Syndrome
References
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Further Reading

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Keywords

Osler-Weber-Rendu syndrome, hereditary hemorrhagic telangiectasia, HHT, Rendu-Osler-Weber syndrome, heredofamilial angiomatosis, familial hemorrhagic angiomatosis, Osler's disease, Osler disease, multiorgan arteriovenous malformation, AVM, treatment, diagnosis, symptoms

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Contributor Information and Disclosures

Author

Lawrence C Wolfe, MD, Senior Associate in Pediatric Hematology/Oncology, Schneider Children's Hospital
Lawrence C Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of Blood Banks, American Society of Hematology, Children's Oncology Group, and Eastern Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Arun Panigrahi, MD, Resident Physician, Department of Pediatrics, Tufts University School of Medicine
Arun Panigrahi, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

Sharada A Sarnaik, MBBS, Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan
Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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