Bevacizumab Results in Complete and Prolonged Cessation of Refractory Bleeding from Gastrointestinal Arteriovenous Malformations Even after Treatment Discontinuation

Background:

Vascular malformations, including GI angiodysplasias, frequently cause recurrent GI bleeding, especially in elderly patients. Their etiology remains unclear, but they are associated with aging, aortic stenosis, end-stage renal disease (ESRD), and von Willebrand disease. While most patients are managed with endoscopic interventions or conservative measures, some experience refractory symptoms necessitating systemic therapy.

Case Presentation:

A 62-year-old male with ESRD on hemodialysis, presented with fatigue and melena, with a hemoglobin of 5.1 g/dL. He had multiple admissions for symptomatic anemia requiring transfusions over the past year. Endoscopy during these presentations showed multiple angioectasia in the stomach and duodenum, treated with argon plasma coagulation. Despite these interventions, he continued to experience GI bleeding, necessitating multiple transfusions.

During his current admission, a capsule study indicated dark blood approximately one hour and thirty minutes after the beginning of the duodenum. Endoscopy revealed gastric vascular ectasias and non-bleeding angioectasias in the duodenum treated endoscopically with thermal therapy and argon plasma coagulation. His persistent bleeding was thought to be in the setting of uremic platelet dysfunction from ESRD. He received numerous medical therapies including octreotide, epoetin alfa, intravenous iron and estradiol without success. He received 24 units of packed red blood cells (PRBC) during a 57-day hospitalization and a total of 40 units PRBC in the past year.

Due to the refractory nature of his bleeding, bevacizumab was selected for systemic treatment. He was started on bevacizumab 5 mg/kg IV, with biweekly dosing for eight weeks, followed by monthly dosing. He received a total of 11 doses of planned therapy. The patient experienced a dramatic response with complete cessation of GI bleeding and is now transfusion independent for 19 months. He maintains a stable hemoglobin of more than 10g/dL for the last 10 months off bevacizumab therapy. His treatment was complicated only by epistaxis, which improved with the temporary cessation of bevacizumab.

Discussion:

ESRD is associated with an increased incidence of bleeding from GI angiodysplasias, which can occur throughout the GI tract. Treatment strategies include endoscopic treatments, angiographic embolization, hormonal therapy, somatostatin analogues, and angiogenesis inhibitors like bevacizumab.

Bevacizumab, a humanized monoclonal antibody targeting VEGF, is approved for treating various cancers due to its anti-angiogenic properties. Limited data exists for its use in bleeding disorders. Previous reports have shown favourable responses in patients with refractory bleeding from angiodysplasias and it has orphan drug designation for hereditary hemorrhagic telangiectasia. The usual dose ranges from 5-10 mg/kg every 2-4 weeks, with reported side effects including hypertension, fatigue, proteinuria, and arthralgia.

Our case is particularly unique because, although there are case reports of successful treatment of AVM bleeding with bevacizumab there are no cases detailing ongoing resolution of bleeding after treatment discontinuation. Our patient is now >10 months off therapy with ongoing stable hemoglobin. This finding has important implications in terms of treatment duration as treatment discontinuation may avoid development of complications and result in healthcare cost-savings.

Conclusion:

This case represents a novel use of bevacizumab for managing transfusion-dependent, refractory anemia secondary to GI angiodysplasia in patients with ESRD. Further studies are needed to establish optimal dosing schedules, and whether treatment can be discontinued safely in stable patients.

No relevant conflicts of interest to declare.