Clinical management of congenital thrombotic thrombocytopenic purpura in Latin America: Expert consensus from a modified Delphi panel

Abstract Background Congenital thrombotic thrombocytopenic purpura (cTTP), also referred to 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. Although international guidelines on the management of TTP and/or thrombotic microangiopathy often contain sections addressing cTTP, specific guidance on cTTP management remains limited. Moreover, approaches to patient care are likely shaped by geographical factors, since access and barriers to care may differ by region. We aimed to explore how healthcare professionals (HCPs) in Latin America (LATAM) diagnose and manage patients with cTTP, with an emphasis on prophylactic treatment, via a consensus-generating exercise. Methods A total of 11 HCPs with cTTP expertise in LATAM (Argentina n=3; Brazil n=3; Columbia n=4; Mexico n=1) completed a three-round modified Delphi panel (July–November 2024). The responses of two other HCPs (Brazil and Mexico) who only partially completed the Delphi panel were also included in the final analysis (i.e., >11 responses were analyzed for some Round 1 and Round 2 statements). 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. Non-Likert scale scoping questions were also included to inform new statements for the next round. Results Consensus from voting panelists was reached on 52 statements covering diagnosis and treatment of cTTP, clinical goals of prophylaxis, identifying patients for prophylaxis, prophylaxis options for cTTP, monitoring of patients receiving prophylaxis, cTTP management in women of childbearing age, patient journey, barriers to prophylaxis, and the need for local resources and guidelines. Panelists agreed that prophylactic, rather than on-demand or reactive, therapy was the most effective way to prevent long-term organ complications (12/12; 100%). However, the current standard of care for prophylaxis (plasma administered at least every 1–2 weeks) does not always provide sufficient protection against acute episodes in all cTTP patients (12/12; 100%). There is a need for alternative prophylactic treatment options if an improvement is not observed with fresh frozen plasma (FFP) prophylaxis (11/11; 100%). Panelists agreed that immediately after resolution of an acute TTP event, all cTTP patients should receive prophylaxis to prevent a recurrent event in the short term (10/11; 91%). Panelists also agreed that long-term prophylactic treatment to prevent a recurrent event in the short and long term is warranted (9/11; 82%). Panelists concurred that for cTTP patients (adults, pregnant women, children and adolescents, and newborn infants), prophylaxis is recommended over a watch-and-wait strategy (77–92% consensus depending on patient population). Assuming equal access to all prophylaxis options, panelists indicated that recombinant ADAMTS13 would be the first-line prophylactic treatment over FFP and over cryoprecipitate-poor plasma (100% for all patient populations). Key considerations for cTTP patients in remission deciding whether to initiate prophylaxis include tolerability of treatment (11/11; 100%) and financial costs associated with treatment and regular hospital visits (11/11; 100%). Panelists confirmed a need for local guidelines specific to cTTP treatment and management (13/13; 100%). Conclusions Our findings offer important insights into current cTTP clinical management practices in LATAM, and are generally consistent with the latest ISTH guidelines published after the Delphi panel was conducted. This consensus outlines essential factors influencing treatment choices and patient care, with consideration of regional particularities, and may help to guide LATAM physicians caring for patients with cTTP.