Thankyou for your help this week!
This week we had a look at HHT. Our patient was diagnosed with HHT aged 30 after a history of epistaxis was noted. On further questioning she was also found to have cutaneous telangectasia.
Her mother died aged 35 when our patient was old 1 from a ‘brain haemorrhage’, however she also had a history of significant epistaxis and telangectasia. Her grandfather also had recurrent epistaxis, telangectasia and suffered with recurrent GI bleeding.
HHT is a rare systemic disorder of fibrovascular tissue. It is thought to be autosomal dominant with 5 genetic variants, most of which affect the VEG-F beta receptors. The condition results in an overgrowth of blood vessels and abnormal vessel formation. >90% of patients who carry the mutation will have some bleeding, this tends to worsen with age.
It can affect many systems, and can cause problems with GI tract, nasal, lungs, brain, liver and skin. Some mutations have also been associated with juvenile polyposis and primary PAH.
Diagnostic criteria for HHT- curacao criteria.
3 or more criteria met indicate definite HHT
2 criteria met indicate possible HHT
Less than 2 criteria met indicates HHT unlikely
1. recurrent and spontaneous nosebleeds which may be mild to severe
2. Multiple telangectasia on the skin of the hands, lips, face or inside of the nose or mouth. Telangectasia are small blood vessels that appear as bed spots that disappear when push on.
3. AVM (arteriovenous malformations) or telangectasia that affect internal organs such as brain/liver/lungs/gi tract/spinal cord.
4. A family history of a first degree relative who meets the criteria for definite HHT or who has been genetically diagnosed.
Haematologist may often find that they are caring for patients, either by ensuring that they are getting regular iron or blood transfusion, or other treatments, or by coordinating care and ensuring that the patient is being seen by the appropriate specialties for management or screening for complications.
ENT are very often involved for management of epistaxis. This may involve topical treatments. Teaching the patient low pressure packing techniques, cauterisation, or other procedures such as septodermoplasty (skin graft in the nose) or Young’s procedure (surgical closure of the nostrils)
The respiratory team will also be involved. 1/3 of patients with have pulmonary AVMs. This causes a right to left shunt, although they rarely bleed they can an can require coiling. Paradoxical emboli can occur causing stroke or brain abscess. As a result if any patient with known AVM or any unscreened patient requires dental work they should have prophylactic antibiotics. Patients can also develop pulmonary arterial hypertension, this may be primary or can be secondary to liver AVMs causing high output heart failure or recurrent VTE.
The liver team may also be involved. 80% of patients will have liver AVMs, although only 5% will be symptomatic. These can cause portal HTN, biliary disease or high output heart failure.
The gastroenterology team may also be involved. 80% of patients will have lesions on endoscopy, although only 1/3 will have bleeding. Repeated endoscopy with coagulation of these lesions is often necessary. In patients who have juvenile polyposis they will need regular screening endoscopy.
The brain can affected 25% of patients. These can be telangectasia, AVM or venous malformations. Symptoms can include headaches, seizure and ICH.
Patients will need to be closely monitored through any pregnancy, they may require transfusion and problems with bleeding pulmonary AVM can occur. There is a 1% maternal mortality associated with pregnancy in the context of HHT.
Patients with HHT and chronic iron deficiency also appear to be prothrombotic, presumably due to the increase in factor VIII associated with chronic blood loss.
If the patient develops AF with an indication for anticoagulation, although anticoagulation should not be withheld definitive treatment e.g. Definitive treatment for AF +/- left atrial appendage if ongoing anticoagulation is indicated.
When screening a new patient genetic testing should be considered, with screening of first degree relatives if a mutation is found.
A bubble echo to look for pulmonary AVMs should be considered, with a repeat every 5 years if negative. If positive further imaging is required.
MRA brain to look for cerebrovascular defects
Consider liver U/S
General managment will include ensuring adequate b12/folate/iron replacement and if regular transfusion is needed, appropriate vaccination and blood provision.
Drugs that have been used in the treatment of HHT include tranexamic acid, hormone therapy, tamoxifen, raloxifene, thalidomide and bevacizumab(avastin). Bevacizumab is a VEG-F inhibitor which is usually used in malignancies, but small studies and case reports have shown there may be benefit in certain patients with HHT. (Dupuis-girod 2014, JAMA)
Further information can be found in international guidelines for the diagnosis and management of hereditary haemorrhaging telangectasia, journal of medical genetics 2011 faughnan ME, Palma VA, Garcia-Tsao G et al
VASCERN.org – vascular European research network
Geisthoff et al 2015 BJHaem review
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