Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature

Abstract

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.

Fig 1

Platelet count, haematocrit and plasma exchange (× body plasma volume) data prior to the initiation of rituximab therapy. The use of vincristine or staphylococcal protein A columns and the date of splenectomy are indicated.

Fig 2

Platelet count, haematocrit and plasma exchange data immediately prior to the initiation of rituximab and subsequent follow-up. Each ◆ indicates one dose of rituximab (375 mg/m²).

Fig 3

ADAMTS13 inhibitor titres and activity levels (mean ± SD) after the initiation of rituximab therapy. Each ◆ indicates one dose of rituximab (375 mg/m²). The inhibitor titre first showed a decrease by day 21 P < 0·05), while the ADAMTS13 activity level first increased by day 35 and remained in the range of 0·2–0·4 U/ml (P < 0·01).