A 23 year old Caucasian male presented with shortness of breath, hypertension, bloody sputum, and a history of drug abuse (confirmed by urinalysis).

A 23 year old Caucasian male presented with shortness of breath, hypertension, bloody sputum, and a history of drug abuse (confirmed by urinalysis). He was found to have severe kidney injury requiring dialysis, hematuria, proteinuria, anemia and thrombocytopenia. A renal biopsy was performed.

Masson trichrome stain

Edematous intimal expansion

Schistocytes

H&E stain Myxoid / mucoid intimal expansion

Interlobular Artery Stained for Fibrin Trichrome Stain Anti fibrin

H&E stain Thick walls with GBM remodeling

Expanded Subendothelial Zone Obliterative Capillary Remodeling

Swollen Endothelial Cells (Endotheliosis)

TTP-TMA, HUS-TMA and preeclampsia result from injury to endothelial cells Normal glomerular capillary with patent lumen TTP-TMA with platelet-rich thrombus HUS-TMA with subendothelial expansion Preeclampsia with endotheliosis Anti-VEGF therapy with hybrid lesion

Thrombotic Microangiopathy (TMA) Thrombocytopenia, MAHA, fever, neurologic and renal abnormalities; low ADAMTS-13 (<10% actionable) Thrombotic Thrombocytopenic Purpura (TTP) Thrombocytopenia, MAHA and renal abnormalities; > 10% ADAMTS-13 Hemolytic Uremic Syndrome (HUS)

Thrombotic Microangiopathy (TMA) Thrombocytopenia, MAHA, fever, neurologic and renal abnormalities; low ADAMTS-13 (<10% actionable) Thrombotic Thrombocytopenic Purpura (TTP) Thrombocytopenia, MAHA and renal abnormalities; > 10% ADAMTS-13 Hemolytic Uremic Syndrome (HUS) No diarrhea (D- HUS) Diarrhea (D+ HUS) Shiga-toxin producing infection, e.g. E coli Atypical HUS Typical HUS Complement dysregulation Drug abuse Pregnancy associated Prescriptio n drugs Systemic sclerosis Radiation induced APL syndrome Malignant HTN Strep pneumonia HUS Many others

Pathologic Patterns of Thrombotic Microangiopathy TTP-TMA with plateletrich thrombus HUS-TMA with subendothelial expansion Preeclampsia with endotheliosis

Thrombotic Thrombocytopenic Purpura (TTP) Capillary Thrombi Glomeruloid Structure Endothelialized Thrombus

HUS LM Thick walls Fibrinoid Necrosis (H&E) Schistocytes (H&E)

HUS Arterial Lesions Fibrinoid necrosis Intimal expansion obliterating lumen Schistocytes

Thrombotic thrombocytopenic purpura (TTP)- like illness associated with intravenous Opana ER abuse-tennessee, 2012. Centers for Disease Control and Prevention. Morb Mortal Wkly Rep. 2013 Jan 11;62(1):1-4. In August 2012, a nephrologist reported to the Tennessee Department of Health (TDH) three cases of unexplained thrombotic thrombocytopenic purpura (TTP). By the end of October, a total of 15 such cases had been reported. A case-control study determined that the cases were associated with dissolving and injecting tablets of Opana ER (Endo Pharmaceuticals). Note: The cases were described as TTP-like, but the pathology clearly is HUS-type rather than TTP-type TMA.

Opana ER abuse and thrombotic thrombocytopenic purpura (TTP)-like illness: a rising risk factor in illicit drug users. Kapila A, et al. BMJ Case Rep. 2014 Mar 3;2014. From Tennessee Thrombotic microangiopathy and acute kidney injury associated with intravenous abuse of an oral extendedrelease formulation of oxymorphone hydrochloride: kidney biopsy findings and report of 3 cases. Ambruzs JM, Serrell PB, Rahim N, Larsen CP. Am J Kidney Dis. 2014 Jun;63(6):1022-6. Two from Tennessee, one from Idaho Note: The cases were described as TTP-like, but the pathology clearly is HUS-type rather than TTP-type TMA.

Thrombotic microangiopathy and acute kidney injury associated with intravenous abuse of an oral extendedrelease formulation of oxymorphone hydrochloride: kidney biopsy findings and report of 3 cases. Ambruzs JM, Serrell PB, Rahim N, Larsen CP. Am J Kidney Dis. 2014 Jun;63(6):1022-6.

Successful treatment of intravenously abused oral Opana ER-induced thrombotic microangiopathy without plasma exchange. Miller PJ, Farland AM, Knovich MA, Batt KM, Owen J. Am J Hematol. 2014 Jul;89(7):695-7. Resurgence of intravenous Opana as a cause of secondary thrombotic thrombocytopenic purpura. Rane M, Aggarwal A, Banas E, Sharma A. Am J Emerg Med. 2014 Aug;32(8):951.e3-4.

Diagnosis: Hemolytic Uremic Syndrome (HUS) type Thrombotic Microangiopathy (TMA), consistent with Opana-induced TMA