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In the implementation of American Society for Apheresis national guidelines, the decision for therapeutic plasma exchange may be confounded by a clinical presentation that fits both a Category I and IV designation. We report the case of a 45-year-old female who presented with concern for a Category IV disorder, gemcitabine-induced thrombotic microangiopathy, and was ultimately diagnosed with a Category I disorder, idiopathic thrombotic thrombocytopenic purpura. This case highlights the importance of ruling out idiopathic TTP by a thorough evaluation for ADAMTS13 activity and inhibitor, even when an alternate thrombotic microangiopathy diagnosis may be likely., (© 2017 Wiley Periodicals, Inc.)