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Abstract: SA-PO290

Drug-Mediated Thrombotic Microangiopathy Associated with Eltrombopag

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Author

  • Tinawi, Mohammad, Nephrology Specialists PC, Gary, Indiana, United States
Introduction

Eltrombopag is a thrombopoietin-receptor agonist indicated in resistant chronic immune thrombocytopenia (ITP). This is the first report of full-blown biopsy-proven thrombotic microangiopathy (TMA) with acute kidney injury (AKI) and the nephrotic syndrome (NS) in an ITP patient on eltrombopag.

Case Description

65-year-old woman with steroids and immunoglobulins resistant ITP presented with confusion, worsening thrombocytopenia, fever, and AKI. Eltrombopag was started 4 days prior to admission. Three weeks earlier, creatinine was 0.84 mg/dl, and platelets 84,000/uL. On admission, Creatinine was 5.22 mg/dl, and platelets 50,000/uL with schistocytes. LDH was 1,193 U/L. Urine protein-to-creatinine ratio was 6510 mg/g with hyperlipidemia and hypoalbuminemia. Blood and urine cultures, and direct Coombs were negative. Anticardiolipin antibodies, hepatitis B and C, and connective tissue disorders serologies were unremarkable. Pre-plasma exchange ADAMTS13 was normal. Eltrombopag was stopped, IV corticosteroids and hemodialysis (HD) were started. Renal biopsy showed focal cortical necrosis, ischemic changes in the glomerular capillary loops, and focal arteriolar fibrin thrombi with red blood cell fragmentation.
After 7 daily plasma exchange sessions, platelets normalized and confusion resolved. Two months later she was taken off HD.

Discussion

There are four reports of eltrombopag-associated AKI, one was renal limited TMA, another in a patient with antiphospholipid syndrome, and two presented with AKI and NS. In this case report, Naranjo adverse drug reaction probability scale showed a score of 7 or a probable relationship between eltrombopag and TMA. Eltrombopag drug-mediated TMA is uncommon. Drug cessation, corticosteroids, plasma exchange and renal replacement therapy should be considered in the management of this disorder.

Ischemic glomerulus with fibrin thrombi