Expert consensus on the clinical management of congenital thrombotic thrombocytopenic purpura in Asia-Pacific: A modified Delphi panel Free

Background Congenital thrombotic thrombocytopenic purpura (cTTP), also known as Upshaw-Schulman syndrome or hereditary TTP (hTTP), is an ultra-rare inherited deficiency of the von-Willebrand factor (VWF)-cleaving enzyme ADAMTS13, characterized by microvascular thrombosis. Current treatments for managing acute TTP episodes and prophylaxis involve ADAMTS13 supplementation by infusion of fresh frozen plasma (FFP), solvent/detergent-treated FFP, intermediate-purity plasma-derived factor VIII (FVIII) concentrate, and more recently, recombinant ADAMTS13 (rADAMTS13).

Although international guidelines on the management of thrombotic microangiopathy and/or TTP frequently include sections on cTTP, there is limited up-to-date guidance specifically on the clinical management of cTTP. Furthermore, considerations for patient care are likely influenced by geographical factors, as access and barriers to care vary by region. We aimed to understand how healthcare professionals (HCPs) in Asia-Pacific (APAC) diagnose and manage patients with cTTP, with a focus on prophylactic treatment, through a consensus-seeking exercise.

Methods A total of 11 HCPs with cTTP expertise in APAC (Australia n=4; China n=2; Hong Kong n=1; South Korea n=1; Taiwan n=3) participated in a two-round modified Delphi panel (July–November 2024). Questionnaires were distributed through a bespoke Delphi panel web application. Consensus was defined as ≥70% of panelists agreeing or disagreeing on Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised and included in the next round. Scoping questions were also included to inform subsequent new statements.

Results Consensus from 11 voting panelists was reached on 46 statements covering diagnosis and treatment of cTTP, clinical goals of prophylaxis, identification of patients for prophylaxis, prophylaxis options for cTTP, monitoring of patients receiving prophylaxis, cTTP management in women of childbearing age, the patient journey, barriers to prophylaxis, and the need for local resources and guidelines.

Panelists confirmed a need for local guidelines focused specifically on cTTP treatment and management (9/10; 90%). Prophylactic, rather than on-demand or reactive, therapy was considered the most effective way to prevent long-term organ complications (10/11; 91%). Most panelists agreed that they would initiate prophylaxis in patients with a history of only one acute TTP episode (10/11; 91%).

Panelists agreed that for all populations with cTTP (adults, pregnant women, children and adolescents, and newborn infants), prophylaxis is recommended over a watch-and-wait strategy (82–91% agreement depending on patient population). Assuming equal access to treatment options, all panelists would recommend rADAMTS13 for prophylaxis.

Panelists indicated that patients with cTTP should be monitored for complete blood count and hemolytic markers at least every month in the first year of prophylaxis (10/11; 91%). In cTTP patients in remission who are not receiving prophylaxis, regular monitoring of complete blood count and hemolytic markers at least every 3 months is necessary so that prophylaxis can be initiated promptly in response to abnormal laboratory results (11/11; 100%).

Common reasons that might cause hesitancy in initiating FFP prophylaxis in patients with cTTP were patient willingness and treatment tolerability. Panelists agreed that patients would be more likely to accept prophylactic treatment if it could be self-administered at home rather than HCP-administered in clinicals/hospitals (11/11; 100%).

Conclusions Our findings provide valuable insights into current practices in APAC and are consistent with the latest ISTH guidelines which were published after the Delphi panel concluded. This consensus may help to guide physicians caring for patients with cTTP in APAC, outlining key considerations in treatment decision-making and patient management, with attention to region-specific factors.