Winning Abstracts from the 2009 Medical Student Abstract Competition: Use Of The Monoclonal Antibody Rituximab For Refractory Thrombotic Thrombocytopenic Purpura
Authors: Amie Jackson, MD, Gregory Monohan MD
Dr. Jackson recently graduated the University of Kentucky and will begin her Internal Medicine residency at Barnes Jewish Hospital in St. Louis
A 53 year old female presented for elective aorto-bifemoral bypass secondary to atherosclerotic infrarenal aortic occlusion. Her past medical history was significant for idiopathic thrombocytopenic purpura at age 20, and hemolytic uremic syndrome with refractory thrombocytopenia requiring plasma exchange at age 49.
The bypass was successful, with no intraoperative complications. Postoperatively, the patient experienced a rapid decrease in platelet count, from 400K/cmm preoperatively to 15K on postoperative day (POD) three, which persisted for over one week without recovery. At that time platelet factor 4 antibody was detected in the patientís serum by ELISA and she was initiated on argatroban for heparin-induced thrombocytopenia. This was followed by a marked increase in schistocytes on peripheral smear, with persistent thrombocytopenia and anemia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made, argatroban was discontinued, and the patient was initiated on plasma exchange utilizing fresh frozen plasma as the replacement product. She had a good clinical response with recovery of platelet count to 377 K/cmm. She was discharged home, but relapsed on post-discharge day five with platelet count of 22K. Her count recovered to supratherapeutic levels with five days of plasma exchange followed by a three week taper. However, after completion of the taper, her platelet count steadily declined over 4 weeks to 112K/cmm. Plasma exchange was initiated a third time, again with resolution of her thrombocytopenia. Because of her relapsing course, it was decided to give the patient four weekly doses of Rituximab at 375 mg/m2 during the tapering phase of plasma exchange. This was successful in maintaining the patientsí platelet counts within normal limits. She has since remained in remission from TTP for over one year from her last plasma exchange.
TTP is a rare disorder that was almost universally fatal prior to the use of plasma exchange therapy. Plasma exchange has dramatically improved prognosis for TTP, with an attendant decrease in mortality from 90 to less than 20 percent. However, 10 to 20 percent of patients have absent or poor response to plasma exchange. Numerous therapeutic options have been tried for patients with exchange refractory disease, with variable success. The association of idiopathic TTP with auto-antibody inhibitors to a protease known as ADAMTS-13 has prompted trials of the anti-CD20 antibody Rituximab for treatment of refractory TTP. We report a case in which a patient with refractory TTP achieved durable remission with the addition of rituximab to plasma exchange.
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