Acquired thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, in addition to variable fever and neurologic and renal dysfunction, without an underlying cause. Recent advances in elucidating the pathophysiology of acquired TTP have led to new testing that we have incorporated into our current management of patients with suspected acquired TTP. Despite these developments, much of the treatment for acquired TTP beyond therapeutic plasma exchange (TPE) is based on low-quality evidence. Our group has a sustained interest in studying and optimizing the use of TPE, along with other concurrent therapies, in acquired TTP patients. Described herein is a summary of how our apheresis consult service approaches requests for TPE in patients with suspected acquired TTP.