Antithrombotic Therapy in Hereditary Hemorrhagic Telangiectasia: Real-World Data from the Gemelli Hospital HHT Registry

Abstract

Although Hereditary Hemorrhagic Telangiectasia (HHT) is characterized by an overwhelming bleeding propensity, patients with this disease may also present medical conditions that require antithrombotic therapy (AT). However, precise information on indications, dosage, duration, effectiveness, and safety of AT in HHT patients is lacking. We performed a retrospective analysis of the HHT Registry of our University Hospital and found 26 patients who received AT for a total of 30 courses (19 courses of anticoagulant therapy and 11 courses of antiplatelet therapy). Indications to treatments included: atrial fibrillation, venous thrombosis and pulmonary embolism, heart valve replacement, retinal artery occlusion, secondary prevention after either stroke or myocardial infarction, and thromboprophylaxis for surgery. The total time of exposure to antiplatelet therapy was 385 months and to anticoagulant therapy 169 months. AT was generally well tolerated, with no fatal bleedings and no significant changes in hemoglobin levels. However, we found three major bleedings, with an incidence rate of 6.5 per 100 patients per year. When only patients treated with anticoagulants were considered, the incidence rate of major bleedings increased to 21.6 per 100 patients per year. Our study indicates that major bleeding may occur in HHT patients receiving AT, with a substantially increased rate in those treated with anticoagulants. Further studies are needed to fully estimate the tolerability of antithrombotic drugs in HHT.

Unsupervised machine learning algorithms identify expected haemorrhage relationships but define unexplained coagulation profiles mapping to thrombotic phenotypes in hereditary haemorrhagic telangiectasia

“…CBC and iron profiles fitted with expected pathophysiological models, but four distinct coagulation profiles and three distinct combined iron-coagulation pro-files could not be explained by current, clinically recognised features, suggesting other drivers of these differences. While bleeding-iron deficiency considerations are centre stage in HHT, modified coagulation is not despite high rates of VTE [27,39], and the challenging risk-benefit considerations when using anticoagulation therapy [40][41][42][43].…”

A Rare Case of Upper Gastrointestinal Bleeding: Osler-Weber-Rendu Syndrome

“…Even though these symptoms occur only in 8% of patients, some of them may be life-threatening, and while diagnosing HHT, a hypothetical liver involvement should be taken into consideration [ 55 , 56 ]. HAVMs are significantly more frequent in patients who had the HHT2 genotype than in patients who had the HHT1 genotype [ 9 , 10 , 11 , 57 , 60 , 61 , 62 ]. The complications of liver involvement of HHT include high-output heart failure, portal hypertension and cirrhosis [ 63 ].…”

“…Cerebral arteriovenous malformations [CAVMs] are more common in patients with HHT1 than HHT2 [ 9 ]. CAVMs affect approximately 10% of HHT patients.…”

“…HHT is estimated to affect approximately 1 in 5000–6000 Europeans [ 7 , 8 ]. More than 76–80% of all cases of HHT are due to mutations in either ENG or ACVRL1 [ 9 , 10 ]. HHT-related GI bleeding develops in approximately 13–30% of HHT patients, typically manifesting in the fifth and sixth decades [ 10 , 11 , 12 ].…”

Hereditary Hemorrhagic Telangiectasia Associating Neuropsychiatric Manifestations with a Significant Impact on Disease Management—Case Report and Literature Review

“…Patient support groups/patient associations are proven to be very effective in helping all rare disease patients, in general, to better cope with their illness; unfortunately, in our case, the patient did not agree to be referred to a rare disease organization and no specific HHT patient group was locally available. The current guidelines for the approach to HHT [ 10 , 63 ] and research evidence show a broadening spectrum of therapeutic solutions like well-known or repurposed drugs (including bevacizumab, propranolol, pazopanib, tacrolimus, and antithrombotic drugs) and new surgical techniques [ 64 , 65 , 66 , 67 , 68 , 69 ]. These would require more supporting evidence on efficacy and standardized algorithms for clinical use.…”