Targeting the inhibitor of ADAMTS13 in thrombotic thrombocytopenic purpura

Abstract

There has clearly been an evolution in the treatment of thrombotic thrombocytopenic purpura (TTP) over the past several years based upon a better understanding of the pathophysiology of this disorder. An autoantibody inhibitor of the ADAMTS13 protease and the resulting severe deficiency of ADAMTS13 function seem to be significant risk factors for the development of TTP, a disease increasingly recognized as an autoimmune disorder. Immune-based therapy aimed at suppressing the inhibitor of ADAMTS13 has been applied to the treatment of patients with TTP who are refractory to the standard treatment of plasma exchange and to patients with multiple recurrences of TTP. More recently, immunosuppressive therapy has been used alone as prophylactic therapy to prevent recurrences of acute TTP. This review focuses on the recent developments in the use of rituximab and ciclosporin in the treatment of TTP.

Diagnostic and prognostic values of ADAMTS13 activity measured during daily plasma exchange therapy in patients with acquired thrombotic thrombocytopenic purpura

“…In agreement with previous reports, 17,18,28 the data suggest that most cases of acquired TTP presented with excess amounts of ADAMTS13 inhibitor that cannot be eliminated effectively in a few days of PE therapy. Clinicians should make effort to order ADAMTS13 work-up on the pretreatment samples to obtain a more reliable laboratory result.…”

“…The data from our study demonstrated that in more than 78% (14/18) of the cases, the samples taken prior PE Procedure 4 correctly classify patients for diagnosis of TTP. In agreement with previous reports, the data suggest that most cases of acquired TTP presented with excess amounts of ADAMTS13 inhibitor that cannot be eliminated effectively in a few days of PE therapy. Clinicians should make effort to order ADAMTS13 work‐up on the pretreatment samples to obtain a more reliable laboratory result.…”

Rapid response and sustained remission by rituximab in four cases of plasma-exchange-failed acute thrombotic thrombocytopenic purpura

“…All patients responded to treatment. Median time to response after the first dose of rituximab was 10 days (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). In particular, the achievement of a platelet count higher than 100.00/lL and a near to full normalization of hemolytic parameters, were observed in 2, 1 and 1 patients after the first, second and third weekly doses of rituximab, respectively.…”

“…In particular, the achievement of a platelet count higher than 100.00/lL and a near to full normalization of hemolytic parameters, were observed in 2, 1 and 1 patients after the first, second and third weekly doses of rituximab, respectively. To date, all the patients are well and active, being free of TTP relapse after a median follow-up of 10 months (4)(5)(6)(7)(8)(9)(10)(11)(12). Recent advances in our understanding of idiopathic TTP have provided a rationale for the use of rituximab to achieve an effective B-cell depletion and clinical improvement in acute autoimmune TTP [2,8,9], which is attributed to the production of anti-ADAMTS13 autoantibodies.…”

“…To date, all the patients are well and active, being free of TTP relapse after a median follow-up of 10 months (4)(5)(6)(7)(8)(9)(10)(11)(12). Recent advances in our understanding of idiopathic TTP have provided a rationale for the use of rituximab to achieve an effective B-cell depletion and clinical improvement in acute autoimmune TTP [2,8,9], which is attributed to the production of anti-ADAMTS13 autoantibodies. Therefore, rituximab has been reported as a useful addition to PE treatment in TTP, although its exact role, dosing need and the best appropriate time to administration remain to establish by prospective studies.…”