Dr Zhan Yi Lim1, Dr David Nolan2, Dr Khalil Patankar3
1Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth, Australia, 2Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia, 3Department of Renal Medicine, Royal Perth Hospital, Perth, Australia
Biography:
Zhan is a nephrologist at Fiona Stanley Hospital, currently completing a Master of Public Health at the University of Edinburgh with a focus on non-communicable diseases, particularly chronic kidney disease.
Background:
Eltrombopag is an oral thrombopoietin-receptor agonist (TPO-RA) used to treat refractory immune thrombocytopenia (ITP). Eltrombopag-related antiphospholipid syndrome (APS) and kidney injury including renal vein thrombosis and nephrotic syndrome have been reported in the literature, with evidence of thrombotic microangiopathy (TMA) as a prominent pathogenic mechanism. We report a case of eltrombopag-associated APS and biopsy-proven TMA with cardiac and renal involvement.
Case Report:
A 58-year-old male patient with relapsed ITP had undergone several lines of treatment, including IVIG, corticosteroids, rituximab, and, most recently, eltrombopag at 50 mg daily. Three weeks after completing eltrombopag, he presented with fatigue and dyspnoea. Physical examination revealed diffuse chest crackles and bilateral lower limb oedema. Laboratory evaluation demonstrated severe acute kidney injury with elevated serum creatinine at 397 µmol/L (eGFR 13 mL/min/1.73 m²), microhaematuria and proteinuria (protein-to-creatinine ratio 60 mg/mmol). The patient deteriorated rapidly with anuria and acute pulmonary edema, necessitating ICU admission for non-invasive ventilation and continuous renal replacement therapy.
Subsequent evaluation showed strongly positive antiphospholipid (aPL) antibodies, normal LDH and ADAMTS13 activity with raised haptoglobins. The patient was treated for probable catastrophic antiphospholipid syndrome with enoxaparin (1 mg/kg) and plasmapheresis.
Following five uncomplicated plasmapheresis sessions, unheralded VF cardiac arrest occurred on day +11. Coronary angiography showed no obstructive disease. Myocardial perfusion scan and FDG PET-CT demonstrated segmental systolic dysfunction (LVEF 35%), fixed perfusion defects with prominent FDG uptake within LV consistent with myocarditis. Repeat testing for aPL antibodies was negative on day +12.
Kidney biopsy on day +18 revealed chronic TMA with moderate mesangiolysis, severe arteriolopathic changes and thickened glomerular basement membranes.
Conclusions:
This case highlighted potential life-threatening APS and TMA complications following eltrombopag treatment for ITP.