Thalidomide and Sucralfate Reduce Gastrointestinal Bleeding in Adults with Hereditary Hemorrhagic Telangiectasia: The Mexican Experience

Introduction Hereditary hemorrhagic telangiectasia (HHT) is the second most common inherited bleeding disorder, occurring in 1/5,000 to 1/10,000 persons. Has an autosomal dominant transmission and can occur de novo. Telangiectases occurs at characteristics sites: lips, oral cavity, fingers and nose; but visceral lesions are common, affecting gastrointestinal tract (GIT), liver, lung, brain and spinal arteriovenous formations. Nosebleed and GIT can lead to iron deficiency anemia. HHT is an underrecognized disease and delay in diagnose can increase morbidity and mortality as more telangiectases develop with aging. Thalidomide treatment for moderate and severe bleedings, that are defined by requirements of intravenous iron replacement and/or transfusions, has been used since more than a decade with good results (Blood 2021;137:888-895 and Hematology Am Soc Educ Program 2021;1:469-477).

Material and methods Anemic adults with HHT based in Curaçao clinical diagnosis criteria, three to four from: a) telangiectases, b) epistaxis, c) visceral involvement and d) direct family history (Am J Med Genet 2009;91:66-67); and positive endoscopic study with moderate to severe GIT bleeding; some patients had a full body CT Scan and showed telangiectasi in al GIT as in Figure 1, the bone window reveal fill blooded telangiectasia. Thalidomide was initiated at 100 mg daily for a month and increased to 200 mg daily if tolerated for 12 months; aspirin 100 mg daily for thrombosis prevention; and omeprazole 20 mg with sucralfate 1 gr twice a day for GIT mucosal protection; transfusion to maintain hemoglobin level at 7-8 g/L and iron carboxymaltose to increase Hb levels and maintain ferritin above 50 ng/mL End points before and after treatment: a) number of episodes of GIT bleeding, b) number of red blood cells transfusions, and c) hemoglobin levels.

Results Fifteen patients were included, 9 men and 6 females. Age from 28 to 74 years, median 56. All patients tolerated thalidomide 200 mg daily with minimum side effects and no hematologic toxicity, and completed 12 months period. The number episodes per month of GIT bleeding for all the group before treatment were 28, all patients have at least one monthly episode and two patients more than three; after three months and until end of treatment the number of episodes per month reduced to 5 for all the group. The number of red blood cells transfusion for all the group before treatment were 65 units per month, after three months of treatment reduced to 9 units and at end of treatment to 4 units. The mean of Hb level before treatment were 5.86 g/L, after three months of treatment were 9.2 g/L, and at end of treatment were 11.7 g/L. As a secondary observation the nosebleed episodes were reduced to zero after three months of treatment, from 9 episodes before treatment. No thrombotic complications were observed. Median time to increase the GIT bleeding was 9 months after end of treatment.

Discussion In HHT, GIT bleeding is a common symptom in older adults over than 50 years due many factors: nosebleed had received various lines of treatment, ageing of the GIT mucosa that leads to the development of more telangiectases and use of medications for chronic diseases, among others. In this case thalidomide with sucralfate are tolerated and have very good results diminishing the GIT bleeding and the red blood cells transfusions, allowing to increase the Hb levels using IV iron. The response is observed in the three first months of treatment and is maintained until nine months after the end of it. Thalidomide as antiangiogenic and Sucralfate as a local healing substance are useful as an option in this kind of patients in low income countries because Bevacizumab, Pomalidomide and other antiangiogenics are more expensive. More trials using thalidome alone or in combination would help to have strong data in results and improve the quality of life of these patients. Finally, after ellectronic search this is the only Mexican experience in the treatment of HHT.

No relevant conflicts of interest to declare.