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A young woman presented with acute right flank pain, fever and thrombocytopenia. Initial evaluation suggested pyelonephritis, supported by flank tenderness, elevated C-reactive protein, and Eschericia coli in urine culture. Broad-spectrum antibiotics were initiated. Over the following 2 days, she developed progressive anaemia and severe thrombocytopenia with biochemical evidence of haemolysis. Differential diagnoses included infection-related haemolysis, atypical haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura (TTP) and drug-induced thrombotic microangiopathy (TMA). Initial imaging was inconclusive, while follow-up CT later during admission demonstrated findings consistent with pyelonephritis, but haematological deterioration was disproportionate. ADAMTS13 enzymatic activity was normal, excluding classic TTP, and a drug screen confirmed recent cocaine use. Microscopy revealed schistocytes, consistent with TMA. The patient’s condition progressed rapidly with marked anaemia and thrombocytopenia by day 3. She was transferred to a tertiary specialised centre on day 4, improved with supportive care alone and achieved full recovery on day 8. This case emphasises the importance of recognising drug-induced TMA and distinguishing it from primary forms to guide appropriate management.