Pharmacological Therapy for Recurrent Obscure Gastrointestinal Bleeding

Obscure gastrointestinal bleeding (OGIB) is defined as occult or overt bleeding of unknown origin that persists or recurs despite negative primary radiological and endoscopic studies. It can be classified into two different clinical forms: obscure-overt OGIB, defined as visible passage of blood (ie, melena or hematochezia) and obscure-occult OGIB, manifested by irondeficiency anemia or positive fecal occult blood test without other evidence of bleeding.1 Since the source of bleeding is not readily identifiable by upper GI endoscopy and colonoscopy, OGIB is therefore, by definition, recurrent. Approximately, 5% of GI bleeding occurs between the ligament of Treitz and the ileocecal valve. Angiodysplasias of the small bowel account for 30% to 40% of OGIB and are the most common source of bleeding in patients over 60 years.1,2 They can be found as a primary disease or a gastrointestinal manifestation of systemic diseases such as hereditary haemorrhagic telangiectasia (HHT), von Willebrand (vW) disease, cardiac valvular disease, radiation enteritis, end-stage renal disease, portal hypertension, connective tissue diseases or vasculitis. Other causes include non-steroidal anti-inflammatory drugs enteropathy, inflammatory bowel disease, small bowel tumors (ie, leiomyomas, carcinoid, lymphomas, adenocarcinomas), Meckel ́s diverticulum or Dieulafoy ́s lesion. Over the last decade, the diagnostic yield and therapeutic capabilities of small bowel endoscopy have dramatically changed with the development of video capsule endoscopy and deep enteroscopy systems (single balloon, double balloon or spiral). Nonetheless, the diagnostic yield is 75% at best combining both techniques, so a quarter of patients lack a diagnosis of the source of bleeding despite exhaustive evaluation and may be at high risk of rebleeding.1 Additionally, a variable percentage of patients with a diagnosis may not respond to endoscopic therapy or may not be tributary to aggressive endoscopic or surgical management due to severe comorbidities or diffuse distribution of lesions throughout the GI tract. In this particular subset of patients, medical therapy is commonly required to stop, or at least, ameliorate bleeding, which usually leads to high transfusional requirements, exacerbations of medical conditions and subsequent hospital admissions. Indications for medical therapy in OGIB, as approved in the latest American Gastroenterology Association technical review, are listed in Table 1.2