Approach to the management of TTP. For patients presenting with microangiopathic hemolysis without another obvious cause, start PEX promptly for a presumed diagnosis of TTP. ADAMTS13 activity and inhibitor testing should be sent before starting PEX, which can affect the results. We start corticosteroids as an adjunct to PEX in all patients and rituximab for patients who have severe symptoms (neurologic or cardiac involvement) or a suboptimal response for PEX (no doubling of platelet count in 4-5 days). PEX can be stopped or tapered once platelet count has been normal (>150 × 10⁹/L) on 2 occasions at least 24 hours apart, and steroids can be tapered. For patients with refractory TTP or worsening thrombocytopenia after an initial response, we recommend verifying that ADAMTS13 activity is <10% before starting PEX (if available), ruling out infections or medications that can contribute to thrombocytopenia and then considering therapy with rituximab (if not already started). For TTP that is refractory to these measures, other immunosuppressants such as cyclosporine, cyclophosphamide, and bortezomib, or even splenectomy, may be considered. aHUS, atypical hemolytic uremic syndrome; CBC, complete blood count; LDH, lactate dehydrogenase; MAHA, microangiopathic hemolytic anemia; PV, plasma volume.