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Blood 2017 Feb 16;129(7):896-905

A mechanistic investigation of thrombotic microangiopathy associated with intravenous abuse of Opana ER.

Hunt R, Yalamanoglu A, Tumlin J, Schiller T, Baek JH, Wu A, Fogo AB, Yang H, Wong E, Miller P, Buehler PW, Kimchi-Sarfaty C


Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following intravenous abuse of extended release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of three patients and investigate intravenous exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high molecular weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury were found in a group of three patients following recent injection of adulterated extended release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs intravenously administered PEO+. Acute tubular and glomerular renal injury was accompanied by non-heme iron deposition and hypoxia inducible factor-1 alpha upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. Intravenous exposure to the inert ingredients in reformulated extended release oxymorphone can elicit thrombotic microangiopathy. While prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of intravenous drug abuse when presented with cases of thrombotic microangiopathy.

Category: Journal Article
PubMed ID: #27864296 DOI: 10.1182/blood-2016-08-736579
PubMed Central ID: #PMC5314814
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2016-06-03 Entry Last Modified: 2017-07-25