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A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER.
Blood. 2017 02 16; 129(7):896-905.Blood

Abstract

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV 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 3 patients and investigate IV 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 3 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 IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

Authors+Show Affiliations

Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies and.Division of Blood Components and Devices, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.Department of Internal Medicine, University of Tennessee College of Medicine at Chattanooga, Chattanooga, TN.Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies and.Division of Blood Components and Devices, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies and.Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN.Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN.Department of Pediatrics and. Department of Pathology, George Washington School of Medicine and Health Sciences, Washington, DC. Department of Coagulation, Quest Diagnostics/Nichols Institute, Chantilly, VA; and.Section on Hematology and Oncology, Department of Internal Medicine. Section on Pulmonary, Critical Care, Allergy and Immunology, and. Section on Critical Care Medicine, Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC.Division of Blood Components and Devices, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies and.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27864296

Citation

Hunt, Ryan, et al. "A Mechanistic Investigation of Thrombotic Microangiopathy Associated With IV Abuse of Opana ER." Blood, vol. 129, no. 7, 2017, pp. 896-905.
Hunt R, Yalamanoglu A, Tumlin J, et al. A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. Blood. 2017;129(7):896-905.
Hunt, R., Yalamanoglu, A., Tumlin, J., Schiller, T., Baek, J. H., Wu, A., Fogo, A. B., Yang, H., Wong, E., Miller, P., Buehler, P. W., & Kimchi-Sarfaty, C. (2017). A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. Blood, 129(7), 896-905. https://doi.org/10.1182/blood-2016-08-736579
Hunt R, et al. A Mechanistic Investigation of Thrombotic Microangiopathy Associated With IV Abuse of Opana ER. Blood. 2017 02 16;129(7):896-905. PubMed PMID: 27864296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. AU - Hunt,Ryan, AU - Yalamanoglu,Ayla, AU - Tumlin,James, AU - Schiller,Tal, AU - Baek,Jin Hyen, AU - Wu,Andrew, AU - Fogo,Agnes B, AU - Yang,Haichun, AU - Wong,Edward, AU - Miller,Peter, AU - Buehler,Paul W, AU - Kimchi-Sarfaty,Chava, Y1 - 2016/11/18/ PY - 2016/08/31/received PY - 2016/11/07/accepted PY - 2016/11/20/pubmed PY - 2017/8/17/medline PY - 2016/11/20/entrez SP - 896 EP - 905 JF - Blood JO - Blood VL - 129 IS - 7 N2 - Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV 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 3 patients and investigate IV 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 3 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 IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA. SN - 1528-0020 UR - https://www.unboundmedicine.com/medline/citation/27864296/A_mechanistic_investigation_of_thrombotic_microangiopathy_associated_with_IV_abuse_of_Opana_ER_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2016-08-736579 DB - PRIME DP - Unbound Medicine ER -