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

“Myxoid”/ “mucoid” intimal expansion H&E stain

Interlobular Artery Stained for Fibrin Trichrome Stain Anti-fibrin

Thick walls with GBM remodeling H&E stain

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 7

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

Thrombotic Microangiopathy (TMA) Thrombocytopenia, MAHA, fever, neurologic and renal abnormalities; low ADAMTS-13 (<10% actionable) Thrombocytopenia, MAHA and renal abnormalities; > 10% ADAMTS-13 Thrombotic Thrombocytopenic Purpura (TTP) 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 Pregnancy associated Systemic sclerosis APL syndrome Strep pneumonia HUS Drug abuse Prescription drugs Radiation induced Malignant HTN Many others

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

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

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

HUS Arterial Lesions Fibrinoid necrosis Intimal expansion obliterating lumen Schistocytes

Centers for Disease Control and Prevention. 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 extended-release 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 extended-release 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.

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