Case Presentation: A 27-year-old man with history of hypertension and IV drug abuse presented to the emergency department with dyspnea. He reported a three-week history of bilateral lower extremity swelling and one week of fatigue, but had been able to work as an auto mechanic until the day of presentation, when he developed acute dyspnea after work. He admitted to injecting crushed oxymorphone (Opana ER) up to twelve times daily during the last year, including multiple times on the day of presentation.
On presentation, patient was hypertensive with blood pressure of 167/102, tachycardic with heart rate 113, and hypoxic requiring 6L of oxygen via nasal cannula. He appeared in moderate respiratory distress despite supplemental oxygen. Exam revealed bibasilar crackles, an audible S4, bilateral 3+ pitting edema to mid-thighs, and scattered petechiae on bilateral ankles. Initial labs showed creatinine of 6.01, hemoglobin 7.0, platelet count 105, and a urine protein-to-creatinine ratio of 6.0, indicating significant nephrotic-range proteinuria.
Additional workup was obtained to evaluate the etiology of the patient’s renal failure. Patient was diagnosed with Hepatitis C during admission, leading to initial suspicion for Hepatitis C-related glomerulonephropathies, such as mixed cryoglobulinemia or membranous nephropathy. Normal cryoglobulins and complement levels did not support these diagnoses. ANA and ANCA were negative, effectively ruling out lupus nephritis and various vasculitides. Workup of anemia revealed schistocytes on peripheral smear, negative direct Coombs, elevated LDH, and low haptoglobin, consistent with microangiopathic hemolytic anemia (MAHA).
Patient’s renal function continued to decline throughout admission, requiring careful monitoring of hypertension and volume status. He ultimately underwent renal biopsy, which revealed thrombotic microangiopathy (TMA). He required initiation of intermittent hemodialysis during admission and was discharged with outpatient hemodialysis after a one-month hospitalization.
Discussion: Thrombotic microangiopathies involve a variety of clinical features including MAHA, thrombocytopenia, and end-organ damage, frequently in the form of acute kidney injury. Numerous primary TMA syndromes have been identified, including both hereditary and acquired disorders. Drug-induced thrombotic microangiopathy (DITMA) is an uncommon type of acquired TMA.
Various medications and drugs of abuse have been found to cause DITMA. There have been several case reports of DITMA associated with reformulated extended-release oxymorphone that is inappropriately crushed and injected. Extended-release oxymorphone (marketed as Opana ER) was initially introduced in 2006, and was reformulated in 2012 in attempt to make the drug resistant to manipulation for abuse by snorting or injection. It is suspected that inert ingredients used in the reformulated tablets may contribute to the development of DITMA. Given the prevalence of intravenous abuse of this drug and reports of dangerous sequelae such as DITMA, the U.S. Food and Drug Administration recommended removal from the market in June 2017.
Conclusions: Reformulated extended-release oxymorphone is frequently manipulated and used intravenously by IV drug abusers. The injected form of this drug is an uncommon cause of drug-induced thrombotic microangiopathy.