1. 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.

2. Masson trichrome stain

3. Edematous intimal expansion

4. Schistocytes

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

6. Interlobular Artery Stained for Fibrin
Trichrome Stain
Anti-fibrin

7. Thick walls with GBM remodeling
H&E stain

8. Expanded Subendothelial Zone Obliterative Capillary Remodeling

9. Swollen Endothelial Cells (Endotheliosis)

10. 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

11. 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)

12. 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

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

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

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

16. HUS Arterial Lesions Fibrinoid necrosis Intimal expansion
obliterating lumen
Schistocytes

17. 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 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.

18. 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 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 Jun;63(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.

19. 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 Jun;63(6):  

20. 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 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 Aug;32(8):951.e3-4.

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