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.
Yomtovian
Roslyn
R
Department of Pathology, The University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Niklinski
Waldemar
W
Silver
Bernard
B
Sarode
Ravindra
R
Tsai
Han-Mou
HM
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