Service d’hématologie biologique, hôpital Lariboisière, AP-HP, Nord, Université de Paris, Paris, France
Sous l’égide du Centre national de référence des microangiopathies thrombotiques, hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, France
EA3518, Recherche clinique en hématologie, immunologie et transplantation, institut de recherche Saint-Louis, Université de Paris, Paris, France
Normandie Univ, UNIROUEN, U1096, CHU Rouen, service de médecine interne, Rouen, France
Service d’hématologie, hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, France
Thrombotic thrombocytopenic purpura (TTP) is a specific form of thrombotic microangiopathy arising from a severe functional deficiency of ADAMTS13, the specific von Willebrand factor (VWF) cleaving protease. This defect leads to the accumulation of hyperadhesive VWF high molecular weight multimers and to the spontaneous formation of microthrombi in the microcirculation, accompanied by peripheral thrombocytopenia and mechanical hemolytic anemia. TTP is mainly an acquired disease, most often autoimmune (iTTP) but can also be inherited (cTTP) when deleterious bi-allelic mutations are found in the ADAMTS13 gene (Upshaw-Schulman syndrome). TTP is a relapsing-remitting disease requiring long-term follow-up. TTP is either idiopathic (50%) or associated to a physiological or pathological context such as pregnancy, autoimmune disease, infection, neoplasia or transplantation. TTP is a disease whose diagnosis and management have changed dramatically over the last 30 years, mainly due to break-throughs in the understanding of the VWF/ADAMTS couple. TTP is a therapeutic emergency, and can be detected by clinical prediction scores (French Score, PLASMIC Score); however, the formal diagnosis relies on the measurement of ADAMTS13 activity, which is expected to be <10 IU/dL. Biological confirmation should not delay management, particularly the initiation of plasma replacement therapy to provide exogenous ADAMTS13, which is the cornerstone of treatment in the acute phase of TTP. Immunomodulatory therapies, like rituximab (monoclonal antibody to CD20) are also recommended in iTTP. Finally, caplacizumab, a monoclonal antibody targeting the A1 domain of VWF, has recently joined the therapeutic options after very satisfactory results in terms of reduction of morbidity and mortality according to international clinical trials. A recombinant ADAMTS13 is currently being evaluated with promising preliminary results. Innovative tools to explore anti-ADAMTS13 autoimmunity are emerging: ADAMTS13 conformation and anti-ADAMTS13 antibody epitope-mapping. These tools may allow the identification of subgroups of patients of varying severity and consequently lead to their therapeutic stratification.