We report a case of a 22-year-old female with antiphospholipid antibody syndrome (APS) associated with systemic lupus erythematosus in whom cryosupernatant plasma exchange was effective and improved both the refractory venous thrombosis in her legs and relapsing thrombocytopenia. A renal biopsy specimen showed not only features of active lupus nephritis but also renal arteriolar thrombosis which is considered to be a type of thrombotic microangiopathy (TMA). Because a pathological role of unusually large von Willebrand factor (vWF) multimers has been reported in patients with TMA including thrombotic thrombocytopenic purpura, plasma exchange using replacement with cryosupernatant, which is free of unusually large vWF multimers, is likely to be an option of treatment modality for patients with refractory and chronic relapsing APS manifesting TMA.