Acute thrombotic thrombocytopenic purpura (TTP) is an aggressive thrombotic microangiopathy that if not treated, can have a 90% mortality rate. Timely, extensive plasma exchange (PEX) has been indicated to reduce the mortality rate to < 10%, but its side effects are not well-known. We present here a case of a patient presented with Comb (+) TTP and developed catheter-associated deep vein thrombosis (DVT).A 27-year-young man presented with persistent thrombocytopenia and Coombs positive anemia was firstly diagnosed with Evans syndrome. However, he was refractory to a methylprednisolone pulse therapy with a combination of platelet transfusion and eventually developed microangiopathy of central nerve system. Several pathological manifestations of the disease were prevented by PEX. The immediate start of PEX (1500 mL/d) induced a complete remission of acquired TTP and disappearance of neurological signs and symptoms. However, external iliac and femoro-popliteal venous thrombosis was diagnosed subsequently, inferior vena cava filter (IVC) filter was immediately implanted accompanied with anticoagulation therapy. Meanwhile, PEX session was sustained as well as oral anticoagulant (rivaroxaban). 14 days later, the patient got full recovery.Catheter-related DVT under the setting of TTP should be cautious. It is necessary to start anticoagulation and antiplatelet therapy for thrombosis early, especially in such cases when PLT count > 50 × 109/L.© 2022. The Author(s).