Extended-release oxymorphone hydrochloride (Opana ER) tablets contain an inert ingredient that can trigger acute microangiopathic hemolytic anemia and thrombocytopenia in those who abuse the drug via intravenous injection, Ryan Hunt, of the Food and Drug Administration, and his colleagues reported.
High-molecular-weight polyethylene oxide appeared to be the cause of acute cases of thrombotic microangiopathy in three patients who were treated in the emergency department of a single hospital in Tennessee. All had chest pain, dyspnea, visual impairment, microangiopathic hemolytic anemia and thrombocytopenia, increased lactate dehydrogenase, and undetectable haptoglobin serum levels. Two patients also had acute renal failure. Plasma exchange therapy was initiated in all three; one required additional hemodialysis.
ADAMTS13 activity was normal in blood samples obtained in two patients before they started plasma exchange. Histologic evidence of thrombotic microangiopathy with endothelial swelling of arterioles and acute tubular injury without deposition of immune complexes was seen in kidney biopsies performed in two patients. In addition, gelatinous material occluded the dialysis catheter and apheresis tubings during the initial plasma exchange sessions, the researchers reported (Blood. 2017;129[7]:896-905).
To test the association of polyethylene oxide with thrombotic microangiopathy, the researchers heated a 40-mg Opana ER tablet cut in several pieces in a spoon with 2 mL water until boiling. They injected guinea pigs with 0.1 or 0.3 mg/kg of the extracted polyethylene oxide, either as a single dose or as five doses given at 1.5-hour intervals. A dose-dependent increase of polyethylene oxide in plasma peaked at 8 hours after the first dose was measured and paralleled with intravascular hemolysis with increased plasma concentration of free hemoglobin, schistocytes in the peripheral blood smear, and thrombocytopenia. Spiking control blood samples in vitro with polyethylene oxide did not result in hemolysis.
“Although injection abuse of prescription opioids is highly concentrated in certain regions of the United States, particularly in rural Appalachia, all physicians should be highly inquisitive of IV drug abuse when presented with cases of [thrombotic microangiopathy],” the researchers concluded.
The researchers had no relevant conflicts of interest. One of the researchers is employed by Quest Diagnostics.
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