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

Abstract

Summary 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.

Current Concepts in Thrombotic Thrombocytopenic Purpura

“…Case reports have described refractory patients that improved within 2 -4 weeks of rituximab therapy (71). Rituximab appears to be valuable for patients that have persistent but low inhibitor titers but may be inadequate for patients with high titers of inhibitors.…”

Rituximab in the treatment of autoimmune haematological disorders

“…In rare cases where plasma exchange is not possible, rituximab treatment may play an important role in alternative treatment (Martin et al, 2007). In the majority of reports in which safety and tolerability are mentioned, rituximab was well tolerated, with few side effects noted during follow-up (Chemnitz et al, 2002;Zheng et al, 2003;Ahmad et al, 2004;Stein et al, 2004;Yomtovian et al, 2004;Fakhouri et al, 2005;Gianfaldoni et al, 2005;Kosugi et al, 2005;Koulova et al, 2005;Benetatos et al, 2006;Schleinitz et al, 2007). Rituximab infusion reactions were reported in some studies, but were generally mild in nature and did not warrant the discontinuation of rituximab (Sallah et al, 2004;Heidel et al, 2007;Scully et al, 2007).…”

Thrombotic Thrombocytopenic Purpura: A Moving Target

“…Responses to rituximab correlate with disappearance of ADAMTS13 inhibitors and a rise of the ADAMTS13 level into the normal range. 32,33 Success with refractory disease suggests that rituximab could be useful for newly diagnosed patients who achieve remission but are at high risk of relapse. 33 Assessing the efficacy of rituximab in this setting may be difficult because the majority of patients do not experience relapses, and the utility of ADAMTS13 data for predicting the risk of relapse is still uncertain.…”