Plasma Exchange Is Not Necessary For The Treatment Of Microangiopathic Hemolytic Anemia Due To Intravenous Opana Abuse

Thrombotic Thrombocytopenic Purpura (TTP) is known to have a deficiency of ADAMTS13 as a feature with very low-to-absent activity as a hallmark of a distinct set of patients with an acquired microangiopathic hemolytic anemia. The working definition for TTP we utilize is a thrombotic microangiopathy and severe ADAMTS13 deficiency which results in the accumulation of ultra large multimers of von Willebrand protein, which results in an aggregation of platelets producing microvascular occlusion and causing some of the “classical” symptoms of TTP including thrombocytopenia, neurologic symptoms, and renal dysfunction.

The treatment for acquired TTP is plasma exchange which is believed to replace the deficient ADAMTS13 and remove anti-ADAMTS13 auto-antibodies. While having demonstrated survival benefit for treatment of TTP, other microangiopathies such as Hemolytic Uremic Syndrome (HUS) do not share the same success.

In January 2013, the CDC reported a TTP-like illness associated with intravenous use of Opana (an extended release oxymorphone). This was initially identified in rural Tennessee. A total of 15 patients were reported. Fourteen of the fifteen patients had reported abusing IV Opana. The median time before presentation of injecting Opana was 1 day with a range of 0-2 days before hospital admission. Twelve of the fifteen patients were treated with plasma exchange. ADAMTS13 was reported on eight of the patients with a range of 84-131% without concurrent infection and 42-199% with concurrent infection. Twelve of the fifteen patients reported chronic Hepatitis C infection or had a positive result during hospital admission.

We report a new series of 11 patients from two rural communities in North Carolina admitted to the hospital with suspicion of TTP. Microangiopathy was confirmed on visualization of peripheral blood films. While we report similar findings compared to the CDC report, we also have demonstrated the ability to withhold plasma exchange in such patients reporting IV Opana use. Although recovery time was variable, improvement in symptoms occurred by withholding the offending agent (IV Opana) and providing supportive care without the use of therapeutic plasma exchange. Our patients ranged in age from 22- 50 years old, 6 males and 5 females, all Caucasian. All of the patients reported recent intravenous Opana abuse (0-5 days prior to presentation). Five were treated initially for sepsis, 3 with generalized pain (chest, back), and all had anemia. Platelet counts ranged from 28,000-121,000/mm³ (mean 66,000/mm³), 9 of the 11 were diagnosed with concurrent Hepatitis C although only 1 knew of prior infection. ADAMTS13 activity ranged from 38-119% with a mean of 65%.

While the specific etiology of intravenous Opana induced microangiopathic hemolytic anemia (MAHA) is unclear, our experience has demonstrated that withholding therapeutic plasma exchange is an acceptable approach to MAHA of this etiology. Though plasma exchange is standard care for TTP, it does not appear to be necessary for treatment of drug induced MAHA related to intravenous Opana use in the absence of markedly deficient ADAMTS13. At our institution the utilization of a rapid assay for ADAMTS13 has resulted in its use as a reliable biomarker for diagnosis of TTP related to anti-ADAMTS13 autoantibodies as opposed to MAHA related to other causes, such as the emerging trend of intravenous Opana use. Withdrawal of the offending agent without the use of therapeutic plasma exchange appears to be an acceptable approach to this specific disorder.