Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature.
Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed 'autoimmune thrombotic thrombocytopenic purpura'. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2-3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors.
Department of Pathology, The University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Roslyn
R
Yomtovian
Waldemar
W
Niklinski
Bernard
B
Silver
Ravindra
R
Sarode
Han-Mou
HM
Tsai
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D002908:Chronic Disease; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008666:Metalloendopeptidases / Q000097:blood / Q000235:genetics; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy* / Q000235:genetics; D012008:Recurrence; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human