Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Abstract

Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ϳ40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases.In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context.In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis. Learning Objectives• Patients with acquired TTP who experience a suboptimal response (refractoriness or disease exacerbation) with standard management need a more intensive treatment • Salvage therapies typically include rituximab, and in the more severe cases twice daily plasma exchange, boluses of cyclophosphamide, vincristine, and splenectomy • A persistent severe acquired ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses

Long-Term Prevention of Congenital Thrombotic Thrombocytopenic Purpura in ADAMTS13 Knockout Mice by Sleeping Beauty Transposon-Mediated Gene Therapy

“…Administration of recombinant ADAMTS13 would be a promising strategy, and phase I clinical trials are underway to evaluate its safety and pharmacokinetics. 14,15 Unfortunately, this treatment is still prophylactic rather than curative.…”

Thrombotic thrombocytopenic purpura: A 5‐year tertiary care centre experience

“…Adjunctive therapies such as immunosuppressive corticosteroids are important in the management of immune mediated TTP. The efficacy of corticosteroids in TTP remains unclear, particularly in the absence of ADAMTS13 testing . In this cohort, the use of corticosteroids in ( n = 25/41) 61.0% was not significantly associated with a survival benefit ( P = .499).…”

“…The standard of care for acquired TTP is daily therapeutic plasma exchange (TPE) . The availability of TPE has dramatically improved the survival of acute TTP, with over‐all survival rates of 80%‐85% reported . However, 20%‐50% of patients relapse within the first 2 years .…”

“…1 The availability of TPE has dramatically improved the survival of acute TTP, 2 with over-all survival rates of 80%-85% reported. 1 However, 20%-50% of patients relapse within the first 2 years. 3 Tertiary care centre: The Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), Johannesburg, South Africa.…”

An improbable and unusual case of thrombotic thrombocytopenia purpura

“…Rituximab, a monoclonal antibody against CD20, has been shown to be effective in treating refractory disease in acquired TPP 9–11. Relapses may occur in approximately 40% of patients (12). One study found that the relapse rate was approximately 36% within a 30-month follow-up period and approximately 76% of those occurred within the first 24 months (13).…”