Incidence of Thromboembolic Disease in Hereditary Hemorrhagic Telangiectasia (Osler Weber Rendu Syndrome)

The Hereditary Hemorrhagic Telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia that affects 1-5000 individuals worldwide. Is characterized by fragile mucocutaneous telangiectasia and vascular malformations in organs such as brain, lungs, liver and the gastrointestinal tract. Nose and gastrointestinal bleeding are remarkable, leading to frequent iron deficiency anemia (IDA) or life threatening bleeding episodes. Venous thromboembolic events (VTE) in HHT are probably more frequent than general population due to high plasmatic levels of FVIII specially in clinical conditions like long time immobilization due to brain abscesses or severe anemia. Additionally, in those patients with pulmonary fistula, the thromboembolic events can produce paradoxal strokes. On the other hand, almost all HHT medical treatments usually used to treat HHT related bleeding could produce thromboembolic disease. Anticoagulation (ACO) in this bleeding condition is a challenge, nevertheless, almost 50% can tolerate it well.

Objective: To report the incidence of VTE in the HHT population.

Methods: Ambispective cohort of adult based on the Institutional Registry of HHT. VTE was defined as the first episode of pulmonary embolism (PE), deep venous thrombosis (VTE) or thrombosis in the fistula sac or the progression of a prior event after its first 48 hs despite anticoagulation.

Result: Over 524 patients 394 adults with HHT confirmed by Curazao criteria or positive genetic test and complete data were included. There were 18 VTE events 4.6% (CI95% 2.7-6.8%), 9 DVT (2.3% IC95% 1.2-4.4%) and 3 PE (0.7% IC95% 0.13-2%). The female gender represents 72%. The median age at the event was 67 years (IIQ 25-75% 56-73).

Five patients (27%) were on ACO prior to the event, mainly for atrial fibrillation, and 3(18%) suffered a previous VTE.

The most frequent risk factors were recent hospitalization (44%) and iron deficiency anemia (44%), immobility (33%), recent surgery (18%), as well as cancer (5%) and recent travel (5%) patient each.Fifteen (83%) patients received ACO, 10(55%) received LMH followed by acenocumarol, 3(30%) of which had to be stopped due to nose or gastrointestinal bleeding.In 5 (27%) a cava vein filter were inserted, of which 3 are under anticoagulation therapy.

Conclusion: VTE incidence in our study was significantly higher than reported in general population at similar age. However, the inclusion of more symptomatic and serious HHT patients could be selection bias. The low number of patients, may influence the results. IDA and hospitalization were the most important associated conditions. Most patients tolerated well the anticoagulation therapy.