An open letter to The Editor from Gaetani et al was recently published in the Orphanet Journal of Rare Diseases. Dr. Gaetani and associates at the Fondazione Policlinico Universitario, Rome Italy, are conducting a study analyzing the safety of antithrombotic therapy (AT) in the treatment of Hereditary Hemorrhagic Telangiectasia (HHT).
AT is a therapy that involves prevention or treatment of harmful blood clots.
The Gaetani letter references the limitations of two earlier studies. Gaetani et al agree with the authors of those studies that additional trials are necessary in order to confirm AT’s efficacy as a therapy for HHT patients.
About the Earlier Studies
One study by Shovlin et al across eight European Reference Network centers assesses the safety of oral anticoagulants in twenty-eight HHT patients.
With respect to the Shovlin study, Gaetani et al noted that patients’ treatment had been initially prescribed by “other physicians.” The study consists of thirty-two cycles treating subsets venous thromboembolism (VTE) or atrial fibrillation (AF). The Shovlin study resulted in an escalation of epistaxis (nose bleeds) in twenty-four of thirty-two treatment cycles. Eleven patients had to discontinue treatment.
The second study conducted by Riera-Mestre et al analyzed the RIETE Registry in an effort to assess therapeutic approaches, clinical characteristics, and outcomes.
In the RIETE study, anticoagulant therapy was administered to twenty-three HHT patients who were diagnosed with VTE. The clinicians discovered that anticoagulants may possibly raise the risk of bleeding. Most cases, however, would not be fatal as the majority of HHT bleeds are not the result of large vascular malformations.
The aforementioned-studies dealt with thrombotic disease in patients with HHT. The studies also covered the issue of insufficient data on AT’s safety.
HHT is a rare disease usually inherited from one parent, which may cause various medical conditions. The most common characteristics are delicate blood vessels that tend to bleed easily. Another name for HHT is Rendu-Osler-Weber disease.
HHT may also cause red or purple clusters to appear on either the skin or on the surface of organs in the body.
The studies currently being conducted are due to uncertainty about the safety of AT as a therapy for HHT and also due to lack of sufficient data.
About The Current HHT/AT Study
Subjects are selected for enrollment who have been diagnosed with HHT and who have received an AT prescription from a physician at the University’s HHT Centre. Twelve participants have been enrolled to date.
The number of bleedings, excessive or minor, will be the primary outcome of the study. A secondary outcome is whether epistaxis (recurrent nose bleeds) increases. The epistaxis severity score (ESS) is used as a guide. At the time the patient is enrolled in the study, hemoglobin measurement will be recorded.
Patients will be monitored with regard to their dependency on blood transfusions or any changes in hemoglobin levels after their initial treatment with AT.
Interim Results of the HHT/AT Study
Approximately seven months after the onset of the HHT/AT study, no significant or unusual bleeding was recorded among the twelve subjects who had received AT therapy.
A slight increase in epistaxis (nose bleeds) was recorded regarding one patient but it was not necessary to discontinue AT therapy for this patient.
Also, either before or after AT was initiated, there were no additional changes of any significance in the ESS measurement or hemoglobin levels. Blood transfusions were not required for any of the subjects.
Strengths and Weaknesses
- On a positive note, contrary to other studies, all patients were given a definite HHT diagnosis
- Doctors who prescribed AT were experienced in cardiovascular and thrombosis diseases as well as AT
- The study results were limited, however, due to the small number of participants
- Another limitation to the study is that the authors indicate that some higher-risk HHT patients may have been denied entry to the study thereby creating a bias.
However, based on these initial data for the safety of AT given to HHT patients, the interim analysis indicates that if experienced physicians prescribe AT for HHT patients in the proper setting, AT should be well tolerated.
Due to the rare nature of HHT, it is difficult to find potential subjects. An additional follow-up and a larger number of HHT patients are needed to confirm these interim results.