From the Guidelines
Refractory Thrombotic Thrombocytopenic Purpura (TTP) management involves escalating therapy with rituximab, caplacizumab, and immunosuppressants, in addition to plasma exchange and corticosteroids, to rapidly control the disease and prevent further morbidity and mortality. The treatment approach for confirmed TTP, as outlined in the kdigo 2024 clinical practice guideline 1, includes plasma exchange, high-dose glucocorticoids, rituximab, and/or caplacizumab.
Key considerations in managing refractory TTP include:
- Adding rituximab to deplete B cells producing ADAMTS13 antibodies
- Initiating caplacizumab to block platelet-VWF interaction and protect platelets
- Considering immunosuppressants such as cyclophosphamide or cyclosporine to reduce autoantibody production
- Monitoring daily platelet counts, LDH levels, and clinical symptoms to adjust therapy based on response
In severely refractory cases, options such as twice-daily plasma exchange, adding bortezomib, or N-acetylcysteine infusion may be considered 1. The goal of treatment is to achieve platelet normalization for at least 2 consecutive days, with gradual tapering of plasma exchange frequency before discontinuation.
The use of caplacizumab, as mentioned in the kdigo 2024 guideline 1, is a crucial addition to the management of refractory TTP, as it rapidly protects platelets and helps control the disease. By combining these therapies, clinicians can effectively manage refractory TTP and improve patient outcomes in terms of morbidity, mortality, and quality of life.
From the FDA Drug Label
The efficacy of CABLIVI for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy was established in a pivotal multicenter, randomized, double-blind, placebo-controlled trial (HERCULES) (NCT02553317)
The management of refractory Thrombotic Thrombocytopenic Purpura (TTP) is not directly addressed in the provided drug labels. However, the labels do discuss the treatment of aTTP using caplacizumab in combination with plasma exchange and immunosuppressive therapy 2, 2, 2.
- The labels mention that caplacizumab is indicated for the treatment of adult patients with aTTP, in combination with plasma exchange and immunosuppressive therapy.
- The HERCULES study demonstrated the efficacy of CABLIVI in reducing the number of patients with TTP-related death, recurrence of TTP, or at least one treatment-emergent major thromboembolic event during the treatment period.
- However, the labels do not provide specific guidance on the management of refractory TTP.
Therefore, based on the available information, it is not possible to provide a definitive answer to the question regarding the management of refractory TTP.
From the Research
Management of Refractory Thrombotic Thrombocytopenic Purpura (TTP)
The management of refractory TTP involves several strategies, including:
- Daily therapeutic plasma exchange (TPE) as the initial treatment, which has transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated TTP, leading to current overall survival rates of >80% 3, 4, 5
- Introduction of rituximab, which has been the second major breakthrough in TTP management, and 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 3, 4, 5
- Salvage strategies for more severe patients, which may include:
- Relapse prevention, which represents a major goal, and can be achieved with the use of rituximab in patients with a severe acquired ADAMTS13 deficiency and otherwise in remission 3, 4, 5
- Emerging therapies, which are currently being evaluated in large, international clinical trials, and include: