Thrombotic Microangiopathy Associated with Oxymorphone Abuse

Thrombotic microangiopathy (TMA) is a devastating disorder that affects vessels in the kidney, brain, and other organs and is often associated with a fatal outcome. TMA has been reported in individuals infusing extended-release oxymorphone tablets (Opana ER) intravenously; this preparation contains high-molecular-weight polyethylene oxide (PEO) and other inert ingredients (PEO+).

To determine whether the opioid itself or the inert ingredients were responsible for TMA, investigators studied three patients with intravenous Opana abuse and infused guinea pigs with varying doses of PEO+.

The patients had chest pain and dyspnea; one had visual impairment with diffuse occlusive disease of the retinal arterioles; two patients were in acute renal failure; and all three had microangiopathic hemolytic anemia and thrombocytopenia. Renal biopsies were consistent with TMA. After treatment with five cycles of plasma exchange, patients had partial or complete recovery of renal function. Intravenous injection of PEO+ in guinea pigs showed dose-dependent microangiopathic hemolytic anemia, consumption of high-molecular-weight multimers of von Willebrand factor, and renal injury. Deposition of iron and PEO in the renal cortex was associated with acute tubular and glomerular injury.