Thrombotic Thrombocytopenic Purpura (TTP) Or TTP-Like Illness Associated With Injection Of Opana ER, Tennessee, 2012

BACKGROUND:   Thrombotic thrombocytopenic purpura (TTP) is a rare but serious blood disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia. The annual incidence in the United States is approximately 1 per 100,000 population. Known risk factors for TTP include infection with Shiga toxin-producing Escherichia coli(STEC) and drug use, including antiplatelet agents, quinine, and cocaine. We investigated an outbreak of TTP and TTP-like illness in Tennessee associated with injection of reformulated Opana ER, an extended-release form of oxymorphone intended solely for oral consumption. 

METHODS:   Following the report of three TTP cases in August 2012, the Tennessee Department of Health (TDH) conducted case finding. A case was defined as microangiopathic hemolytic anemia and thrombocytopenia in a person with an admission platelet count of ≤50,000/µL, in the absence of certain known causes, such as disseminated malignancy and malignant hypertension. TDH investigators interviewed possible cases in person and reviewed medical charts. Controls meeting the inclusion criterion of IV drug abuse in the previous 6 months were recruited from a methadone clinic. 

RESULTS:   Fifteen cases were reported by October 31, 2012 and initial admission date ranged from April 16 to October 20. Seven (47%) cases were in one rural county in northeast Tennessee. Case-patients reported symptoms typical of TTP, including nausea in 79%, abdominal pain in 71%, and fatigue in 64%. Of the 15 cases, 7 were also treated for sepsis including three diagnosed with endocarditis. Clinical characteristics were similar among cases with and without sepsis. Of the 15 case-patients, 14 (93%) reported recent injection of reformulated Opana ER to TDH investigators. The odds of TTP or TTP-like illness were 35.0 times higher among those who reported injection of reformulated Opana ER compared with those who did not report injection of reformulated Opana ER (95% confidence interval = 3.9 – 312.1). 

CONCLUSIONS:   We describe an outbreak of TTP associated with IV drug abuse. Injection of reformulated Opana ER was strongly associated with the illnesses of case-patients. The new formulation of Opana ER was introduced in February 2012, and contains inactive ingredients not found in the original formulation, including polyethylene oxide (PEO). The disease mechanism and extent of the problem is not yet known.