Device-assisted Enteroscopy for Obscure Gastrointestinal Bleeding in the Setting of Thienopyridine Antiplatelet Therapy.

BACKGROUND: Current guidelines recommend suspending thienopyridine therapy 5 to 7 days before therapeutic endoscopy to reduce the risk of bleeding-related complication. However, interruption of antiplatelet therapy may increase the risk of a cardiovascular event. The aim of this study was to evaluate the safety and diagnostic yield of device-assisted enteroscopy (DAE) with endoscopic therapy in patients receiving thienopyridine antiplatelet therapy. MATERIALS AND METHODS: A retrospective chart review was performed for patients treated in the LSU Health Sciences Gastroenterology Clinics between the dates of October 4, 2007 and February 15, 2015. A total of 774 enteroscopy procedures were reviewed to identify patients on active thienopyridine therapy at the time of DAE. RESULTS: During the study period, a total of 68 patients underwent DAE while on thienopyridine therapy. Confirmed or suspected small bowel bleeding was the most common procedural indication. A total of 143 endoscopic interventions were performed, primarily argon plasma coagulation for ablation of intestinal angioectasias. There were no significant bleeding-related complications associated with these procedures. In addition, the diagnostic yield for these procedures was high (77%) with a significant percentage of patients in the thienopyridine group found to have an active bleeding source at the time of DAE. CONCLUSIONS: The performance of DAE procedures with endoscopic intervention such as argon plasma coagulation may be safe in patients on thienopyridine therapy. Continuing thienopyridines may also increase the diagnostic yield of these procedures by promoting active bleeding from the culprit source.

Downregulation of Spry-1, an inhibitor of GDNF/Ret, causes angiotensin II-induced ureteric bud branching.

Mutations of genes in the renin-angiotensin system are associated with congenital abnormalities of the kidney and urinary tract. The major signaling pathway for branching morphogenesis during kidney development is the c-Ret receptor tyrosine kinase whose ligand is GDNF and whose downstream target is Wnt11. We determined whether angiotensin II, an inducer of ureteric bud branching in vitro, influences the GDNF/c-Ret/Wnt11 pathway. Mouse metanephroi were grown in the presence or absence of angiotensin II or an angiotensin type 1 receptor (AT1R) antagonist and gene expression was measured by whole mount in situ hybridization. Angiotensin II induced the expression of c-Ret and Wnt11 in ureteric bud tip cells. GDNF, a Wnt11-regulated gene expressed in the mesenchyme, was also upregulated by angiotensin II but this downregulated Spry1, an endogenous inhibitor of Ret tyrosine kinase activity in an AT1R-dependent manner. Angiotensin II also decreased Spry1 mRNA levels in cultured ureteric bud cells. Exogenous angiotensin II preferentially stimulated ureteric bud tip cell proliferation in vivo while AT1R blockade increased cell apoptosis. Our findings suggest AT1R-mediated inhibition of the Spry1 gene increases c-Ret tyrosine kinase activity leading to upregulation of its downstream target Wnt11. Enhanced Wnt11 expression induces GDNF in adjacent mesenchyme causing focal bursts of ureteric bud tip cell proliferation, decreased tip cell apoptosis and branching.