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Thromb Haemost 2009; 101(02): 233-238
DOI: 10.1160/TH07-12-0753
Theme Issue Article
Schattauer GmbH

Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies

Elena Bresin
1   Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Ranica, Bergamo, Italy
,
Sara Gastoldi
1   Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Ranica, Bergamo, Italy
,
Erica Daina
1   Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Ranica, Bergamo, Italy
,
Daniela Belotti
2   Units of Hematology, Immunohematology and Blood Transfusion Center, “San Gerardo” Hospital, Monza, Italy
,
Enrico Pogliani
2   Units of Hematology, Immunohematology and Blood Transfusion Center, “San Gerardo” Hospital, Monza, Italy
,
Paolo Perseghin
3   Therapeutic Apheresis Unit, “San Gerardo” Hospital, Monza, Italy
,
Potito R. Scalzulli
4   Unit of Hematology, “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy
,
Rossella Paolini
5   Unit of Oncology, Azienda Ospedaliera of Rovigo, Italy
,
Raimondo Marcenò
6   Unit of Transfusion Medicine, “V. Cervello” Hospital, Palermo, Italy
,
Giuseppe Remuzzi
1   Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Ranica, Bergamo, Italy
7   Division of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Italy
,
Miriam Galbusera
1   Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Ranica, Bergamo, Italy
› Author Affiliations
Further Information

Publication History

Received: 27 December 2007

Accepted after major revision: 17 January 2008

Publication Date:
23 November 2017 (online)

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Summary

Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses. Five patients who presented with persistence of undetectable ADAMTS13 activity and high titers of autoantibodies, were treated with rituximab as pre-emptive therapy during remission. Four of them were affected by relapsing TTP and one was treated after the first episode. ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after three months in all patients, and persisted >20% without inhibitors at six months. In three patients disease-free status is still ongoing after 29, 24 and six months, respectively. Relapses were documented in two patients during follow-up: in one patient remission lasted 51 months; while in the other patient relapse occurred after 13 months. Results demonstrated that rituximab used as pre-emptive treatment may be effective in maintaining a sustained remission in patients with anti-ADAMTS13 antibodies in whom other treatments failed to limit the production of inhibitors, and suggests that re-treatment with rituximab should be considered when ADAMTS13 activity decreases and inhibitors reappear into the circulation, to avoid a new relapse.

Keywords

TTP - rituximab - ADAMTS13 - autoantibodies - rare diseases
 

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