From Proteinuria to Platelet Crisis: Nonsteroidal Anti-Inflammatory Drug (NSAID)-Triggered Minimal Change Disease Complicated by Thrombotic Thrombocytopenic Purpura

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA) characterized by thrombocytopenia and organ ischemia due to disseminated microthrombi. While often associated with autoimmune disorders, its occurrence secondary to glomerular diseases like minimal change disease (MCD) is rare. MCD, a podocytopathy marked by proteinuria, hypoalbuminemia, and edema, accounts for only 10–15% of adult idiopathic nephrotic syndrome cases. NSAID-induced MCD is uncommon and primarily seen in older patients. We report a unique case of NSAID-induced MCD in a younger adult, complicated by TTP, highlighting a rare clinical overlap. Case Description: A 40-year-old female with a history of immune thrombocytopenic purpura presented with two months of progressive lower extremity edema. She reported recent use of meloxicam, methocarbamol, and botox injections for migraine management. Despite outpatient diuretic therapy, she developed headaches, visual disturbances, and vomiting. On admission, labs revealed severe thrombocytopenia (platelets 12 x109/L), microangiopathic hemolytic anemia with schistocytes, a negative Coombs test, and nephrotic-range proteinuria (13 g/day). She also tested positive for COVID-19 antigen. She was diagnosed with TTP and treated with high-dose corticosteroids and plasma exchange with fresh frozen plasma, resulting in hematologic recovery. However, her proteinuria persisted. One month later, a renal biopsy revealed minimal change disease with mild podocyte foot process effacement and focal basement membrane thinning. She was treated with rituximab and prednisone, leading to remission of nephrotic syndrome, although ADAMTS13 activity remained persistently decreased. Discussion: This case underscores a rare sequence in which NSAID-induced MCD preceded TTP. While NSAID-associated MCD is documented, it does not typically occur in younger adults. The pathogenesis of MCD involves T-cell dysregulation and podocyte injury. NSAID use may have triggered MCD and concurrent COVID-19 infection further disturbed immune regulation, contributing to autoantibody development against ADAMTS13 and precipitating TTP. Given the scarcity of cases linking MCD and TTP, particularly in the setting of NSAID use and infection, this case highlights the need for clinical vigilance and further research into the immunological interplay between glomerular diseases and TMAs.