The value of combination therapy for refractory ITP is not well defined. We present the case of a 29-year-old male with severe ITP refractory to initial standard therapy including steroids, IVIG, and subsequent splenectomy, who was treated with the combination therapy of rituximab, romiplostim, and mycophenolate and eventually developed thrombocytosis requiring plateletpheresis. Our case highlights the importance of the need to understand predictors of response to standard upfront treatment of acute ITP.