Screening Guidelines

There are hidden manifestations of HHT that can contribute to life-threatening events.

What are Screening Tests?

It is important to gain an understanding of how HHT impacts the internal organs. There are several tests that everyone who is known or suspected to have HHT should have done. These are called screening tests since the abnormality is looked for prior to causing a problem. Lung AVMs and brain VMs are the only problems associated with HHT for which we recommend pre-symptomatic, preventive screening.

A screening test will:

  1. Confirm you meet the criteria for a diagnosis of HHT
  2. Look for pulmonary (lung) AVMs and cerebral (brain) AVMs since these can cause serious life-threatening events without warning
  3. Identify additional areas of impact from HHT

Adult Screening

Pulmonary AVMs (Lung AVMs)

Screening for lung AVMs (PAVM) is dependent on the age of the individual, and to a lesser degree, their symptoms. Preferably, individuals with HHT will have had screening for PAVMs by the time of their early teens. If a pregnant woman with HHT has not had a recent evaluation for PAVM, it is imperative for her to do so as soon as pregnancy is recognized. In many cases, an HHT Treatment Center will be able to use tests performed by another facility unless the original tests are too old, the old test is not of high enough quality, or the old test was performed a little differently.

PAVMs larger than a certain size should be embolized to prevent complications like brain abscesses and strokes. For smaller PAVMs, antibiotics prior to most dental work and certain other non-sterile invasive procedures, like colonoscopy, are recommended. Until PAVMs are excluded by testing, a person over the age of 10 with known or suspected HHT should take antibiotics before all dental cleanings, work and other medical procedures which have a risk of introducing bacteria into the bloodstream.

Clinicians should screen all patients with possible or confirmed HHT for pulmonary AVMs.

Contrast Echocardiogram (bubble echo)

This is the recommended test of choice for PAVM screening in adults and also used in older children and adolescents. This test uses sound waves (ultrasound) to determine if injected saline bubbles can get through the lung circulation and be seen back in the heart, on the left side. This would be called a shunt. It is a very sensitive test but not everyone with a “positive” or “abnormal” bubble echo test has a Pulmonary AVM large enough to require treatment by embolization. To determine if treatment is necessary, a chest CT scan should be done if the bubble echo is more than minimally abnormal.

Chest X-ray

A standard X-ray of the lungs will let doctors look at the size of your heart and the condition of your lungs.

Shunt Test

During this test you breathe pure oxygen for 15 minutes with a nose clip on, then a small sample of arterial blood is collected from an artery in your wrist. This is not a routine screening test, but rather is used to assess a patient before and after treatment for PAVMs.

CT Scan of the Lungs

This is like a 3-dimensional high-resolution X-ray of your lungs. If “X-ray dye” is used, an IV will need to be started.

Pulmonary Angiogram

A catheter is inserted through a large vein in either your leg or neck, and is passed up into the arteries of the lungs. This involves one or more injections of “X-ray dye” into the arteries to expose the AVM.

Brain (Cerebral) VM

The rationale for screening for brain VMs in HHT is that screening will detect a treatable brain VM before the development of a life threatening or debilitating complication.

To screen for brain VM, an MRI with and without gadolinium dye is recommended. Since brain VMs can cause brain hemorrhage in infants, a brain MRI early in life is recommended.

No evidence exists at this time to recommend follow-up screening after an initial negative study during childhood, but consideration should be given to one adulthood MRI following initial negative childhood MRI (Faughnan et al.,2020).

GI Bleeding

  • Mild HHT-related GI bleeding: Patient who meets their hemoglobin goals* with oral iron replacement.
  • Moderate HHT-related GI bleeding: Patient who meets their hemoglobin goals* with IV iron treatment.
  • Severe HHT-related GI bleeding: Patient who does not meet their hemoglobin goals* despite adequate iron replacement or requires blood transfusions.

* Hemoglobin goals should reflect age, gender, symptoms and comorbidities.

An upper endoscopy is the first line diagnostic test for suspected HHT-related bleeding. Patients who meet colorectal cancer screening criteria and patients with a SMAD4 genetic variation (genetically proven or suspected) should also have regular colonoscopies.

Capsule endoscopy is recommended for suspected HHT-related bleeding when upper endoscopy does not reveal significant HHT-related telangiectasia.

Approximately 3% of HHT patients have the SMAD4 mutation and overlap with juvenile polyposis syndrome. These patients are at high risk of colorectal cancer and should be screened frequently starting at age 15. HHT patients without Juvenile Polyposis have colorectal cancer risks like the general population. Patients with the SMAD4 mutation are also at risk for heart and joint problems and require appropriate screening (Faughnan et al.,2020).

Liver VM

Diagnostic testing is recommended for liver VMs in HHT patients with symptoms and/or signs suggestive of complicated liver VMs such as heart failure, pulmonary hypertension, abnormal cardiac biomarkers, abnormal liver function tests, abdominal pain, portal hypertension or encephalopathy.

Doppler ultrasound, CT scan or contrast abdominal MRI are used to diagnose Liver VMs.

  • Doppler ultrasound has been proposed as the preferred first-line investigation for the assessment of liver VMs due to its safety, tolerability, low costs and accuracy for the detection of liver VMs
  • CT has been recommended previously when expertise in Doppler US is lacking for diagnosing liver VMs
  • Magnetic resonance imaging (MRI) of the liver provides excellent accuracy with both multiphase anatomic assessment and hemodynamic characterization of liver VMs

If a liver VM has been detected, echocardiographic evaluation is recommended to see how liver VMs impact heart function.

In those with signs or symptoms of heart failure and an intermediate or high probability of pulmonary hypertension, right-heart catheterization should be performed  to accurately assess cardiac and pulmonary hemodynamics. (Faughnan et al.,2020).

Referral is needed for liver transplant in patients with symptomatic complications of liver VMs.

Liver biopsy should be avoided in any patient with proven or suspected HHT.

Hepatic artery embolization should be avoided in patients with liver VMs as it is associated with significant morbidity and mortality.

Anemia

HHT patients who are adults (regardless of symptoms) and all children with recurrent bleeding and/or symptoms of anemia should be screened annually.

Screening for anemia typically involves: complete blood count (CBC), iron panel (serum iron, total iron binding capacity, transferrin saturation), and ferritin.  A CBC alone could miss underlying iron deficiency without anemia Faughnan et al.,2020).

Policy Statement on Iron Replacement Therapy in HHT

Annual Visit with your Primary Care Physician (PCP)

If you have HHT, a yearly evaluation by your PCP is recommended, along with an annual check of ferritin levels, hematocrit, and hemoglobin. Without periodic check-ups with an HHT expert, HHT related medical problems are often missed, misdiagnosed or mismanaged which can lead to catastrophic events. Most HHT Centers of Excellence will see patients every 3-5 years, or as symptoms warrant.

Pediatric Screening

Pediatric care recommendations:

  • Diagnostic genetic testing should be offered for asymptomatic children of a parent with HHT.
  • Screening for pulmonary AVMs in asymptomatic children with HHT or at risk for HHT at the time of presentation / diagnosis.
  • Large pulmonary AVMs and pulmonary AVMs associated with reduced oxygen saturation should be treated in children to avoid serious complications. 
  • Repeating pulmonary AVM screening in asymptomatic children with HHT or at risk for HHT; typically, at 5-year intervals 
  • And screening for brain VMs in asymptomatic children with HHT, or at risk for HHT, at the time of presentation / diagnosis is recommended. Brain VMs with high risk features should be treated.

According to the Clinical Guidelines, there is no consensus on the recurring tests of children with HHT. However, it is recommended by most HHT Centers that:

  1. Children with possible or confirmed HHT should be screened for Brain VM in the first year of life (or at the time of diagnosis) and at least one follow-up MRI at puberty since brain VM development appears to correlate with times of growth.
  2. Lung AVM screening is recommended every 3-5 years, if a pulse oximetry test result is 97% or higher. If a pulse oximetry result is lower than 97%, or a child is short of breath, additional tests or treatment may be required.

Pulmonary AVM screening

Based on the fact that some children do have complications from PAVMs, HHT medical professionals currently advocate screening for PAVM in all children of a parent who has HHT (HHT International Clinical Guidelines).

  1. Pulse oximetry PLUS chest X-ray.
  2. Transthoracic contrast echocardiography (TTCE; also called bubble echo) has a higher sensitivity as a screening test for pulmonary AVMs. TTCE has the advantage of being a non-radiating test and is the recommended screening test for symptomatic children who have low oxygen levels, complain of shortness of breath, have a hard time keeping up in sports, or have had prior neurologic complications.

When screening tests for PAVMs are positive, CT is the next step to determine where the PAVMs are located and if they are large enough to treat.

References

  1. Lynne Sekarski, MSN, RN, CPN and Lori Spangenberg, BSN, RN. (2011). 'Hereditary Hemorrhagic Telangiectasia: Children Need Screening Too', Pediatric Nursing37(4); 163-168.
  2. Faughnan, M. E. et al.(2020). 'Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia'. Annals of internal medicine173(12), 989–1001. https://doi.org/10.7326/M20-1443

Pregnancy Screening

Pregnant HHT patients should consult an HHT expert to make the best decisions for their specific pregnancy. Each pregnant person with HHT has different symptoms and they will need personalized advice. With the right screening, most women with HHT can have a normal pregnancy and delivery with no more risk than a woman without HHT.

Brain VM Screening

Screening recommendations:

  • Asymptomatic patients do not require routine brain VM screening during pregnancy. 

    • Around 10% of women with HHT will present with asymptomatic brain VM. If a woman has no symptoms, in most cases, treatment of brain VM will be deferred until after pregnancy due to the low risk of bleeding.

  • Pregnant women with HHT who have symptoms suggestive of brain VM, including those with previous brain bleed, should be screened for brain VMs using unenhanced (without gadolinium) MRI in the second trimester

0.5% of unscreened women will present with a brain bleed during pregnancy or after they give birth. In cases of prior bleeding of brain VM, the risk of re-bleeding is increased. This risk is up to 30%, mainly in the 2nd/3rd trimester and after birth.

Pulmonary AVM Screening

During pregnancy there is an increase in cardiac output, an increase in blood volume, and high progesterone levels. This combination can result in enlargement and/or rupture of PAVMs during pregnancy.

PAVMs can occur at any time during pregnancy. 85-90% of complications occur in the second or third trimesters. For previously treated PAVMs, the risk of complications during pregnancy is not precisely known, but may be about ~5%. 

PAVM screening recommendations for pregnant women:

  • In asymptomatic patients, initial pulmonary AVM screening should be performed using either agitated saline transthoracic contrast echocardiography (TTCE) or low-dose non-contrast chest CT, depending on local expertise. Chest CT, when performed, should be done early in the second trimester.
  • In patients with symptoms suggestive of pulmonary AVM, diagnostic testing should be performed using low-dose non-contrast chest CT. This testing can be performed at any gestational age, as clinically indicated.
  • Pulmonary AVMs should be treated starting in the second trimester unless otherwise clinically indicated.

Screening frequency recommendations:

  • Screening and treatment of PAVMs should occur as early as possible at ~12-20 weeks.
  • For patients who have had prior negative PAVM screening, additional screening during pregnancy is not needed in the absence of symptoms. 
  • Pregnant people with HHT who have not been recently screened and/or treated for pulmonary AVM should be screened and treated in pregnancy.

There is a procedural risk for PAVM embolization, which includes bleeding, TIA/stroke, and sedation reaction, but this risk is <1% of cases and are usually minor.

Uterine AVM
  • Uterine AVMs are more likely related to previous uterine procedures
  • Treatment: Uterine artery embolization