HHT

What is HHT?

HHT (Hereditary Hemorrhagic Teleangiectasia), called Osler-Weber-Rendu syndrome,  is an inherited disorder in which small blood vessels develop abnormally [ref 1].  It is estimated that 30,000 to 60,000 people (1 out 5,000 to 10,000) in the United States are affected. Individuals with HHT develop telengiectasias in the skin (usually in the fingers and hands) and the mucosa of the nose and mouth.  Similar abnormal blood vessels (arterial-venous malformations, AVMs) can also develop in internal organs like the lungs, brain, liver and intestines (called ).  The most common symptom of HHT is frequent nose bleeds.  Anemia is also common. AVMs in internal organs can lead to bleeding and infections. 

Why Does Thrombosis Occur in HHT?

Similar to individuals without HHT, patients with HHT may develop DVT and PE associated with the usual transient risk factors, e.g. hospitalization, immobility, major surgery, hormonal therapy and others; associated with obesity, smoking and inherited or acquired thrombophilias; or unprovoked. It is not known whether HHT patients are at higher than usual risk for DVT and PE.  Additional risk factors for thrombosis in people with HHT include use of potentially pro-thrombotic medications.

1. Estrogens are used to decrease bleeding and are well established as risk factors for DVT and PE.
2. Amicar® (aminocaproic acid) and Lysteda® (tranexamic acid), the anti-fibrinolytic drugs, are used for the treatment of HHT patients. While there have been concerns that these drugs may increase the risk for DVT and PE, it is reassuring that recent reports suggest this is not the case [ref 2,3].
3. There is increasing evidence to support the use of Thalidomide and Avastin® (Bevacizumab) to treat bleeding in people with HHT in whom routine medications and interventions have not been effective [ref 4,5,6].
   • Avastin® has been associated with an increased risk for DVT and PE in cancer patients when taken at higher doses [ref 7]. There is no consensus on the best dose to use in HHT patients: lower or similar doses as in cancer patients have been used. It is not known whether Avastin® leads to an increased risk of blood clots in HHT patients at the higher (or lower) doses, but it may well not.
   • Thalidomide: The risk for venous thromboembolism in cancer patients is particularly pronounced if it is given together with steroids. Steroids are not used together with Thalidomide in the treatment of HHT patients. Thus, thrombotic risk in HHT patients treated with Thalidomide may not be an issue.
4. Anemia and the need for blood transfusions may require hospital admission and immobility, which by themselves increase the risk for DVT and PE.
5. Finally, patients with HHT may have disturbances in their coagulation system, such as elevated clotting factor VIII levels, that may increase the risk of DVT and PE [ref 2].

How Common is Thrombosis in HHT?

Data are limited about the prevalence of DVT and PE in individuals with HHT.  The only large published report on thrombosis in HHT patients showed that 6.5 % of patients had a DVT or PE (20 of 309 patients) [ref 8]. This is not unsubstantial.

 

How are DVT and PE Prevented in HHT Patients

The hospitalized and immobile HHT patient typically should be treated with intermittent compression devices (ICDs). In higher risk patients (e.g. after major surgery) prophylactic doses of a s.c. anticoagulant should be considered.

How Are DVT and PE Treated?

Management of HHT patients who have developed a DVT or PE can be very challenging, as bleeding from the abnormal blood vessels in nose and gastrointestinal tract may become much worse when anticoagulants are given [ref 8,9]. Yet, anticoagulants are needed in this situation to prevent thrombus progression and PE.  A thorough assessment of all the patient’s risk factors for venous thromboembolism and those for bleeding is needed to make a solid decision on (a) what drug to use, (b) what intensity of treatment to choose (i.e. target INR in the patient on warfarin) and, importantly, (c) how long to treat with anticoagulants. In the case of an unprovoked DVT or PE, thrombophilia and  D-dimer testing may be helpful to assess the risk of recurrent VTE and help make decisions on length of anticoagulant therapy. Evaluation and management in a specialized HHT Center [ref 1] is probably the best option for these patients to optimally balance the risk of bleeding and recurrent thrombosis.

References

1. http://hht.org/– the website of “HHT Foundation International”
2. Kagoma YK et al. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: A systematic review of randomized trials. Thromb Res 2009;123:687-696.
3. CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial. Lancet 2010;376:23-32.
4. Lebrin, F et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nature Medicine;16:420-428.
5. Brinkerhoff, BT et al. Long-term therapy with bevacizumab in hereditary hemorrhagic teleangiectasia. N Engl J Med 2011;364:688-689.
6. Chen S et al. Safety of intranasal Bevacizumab (avastin) treatment in patients with hereditary hemorrhagic teleangiectasia-associated epistaxis. Laryngoscope. 2011;121:644-646.
7. Nalluri SR et al. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients. A meta-analysis. JAMA 2008;300:2277-2285.
8. Shovlin CL et al. Elevated factor VIII in hereditary haemorrhagic teleangiectasia (HHT): Association with venous thromboembolism. Thromb Haemost 2007;98:1031-1039.
9. Ghosh K et al. Hereditary haemorrhagic teleangiectasia (HHT): Negotiating between the Scylla of bleeding and Charybdis of thrombosis. Thromb Haemost 2008;100:162-164.

For Patients: This same education blog, written for patients and non-health care professionals, can be found here.

Authors: This blog entry was written by Dr. Stephan Moll and Dr. Raj Kasthuri, both at the Hemostasis and Thrombosis Center, University of North Carolina, Chapel Hill, NC.  Dr. Kasthuri is also the Director of the UNC HHT Center of Excellence.

 

Disclosure: The authors have no financial conflict of interest with this education blog.

Last updated: March 1st, 2011