Endothelial dysfunction in thrombotic thrombocytopenic purpura: therapeutic perspectives

Immune Thrombotic Thrombocytopenic Purpura (iTTP) is a rare but severe disease with a mortalityrate of almost 100 % in the absence of adequate treatment. iTTP is caused by a severe deficiency inADAMTS13 activity due to the production of inhibitory antibodies. Age has been shown to be a majorprognostic factor. iTTP patients in the elderly (60yo and over) have more frequent organ involvement, especially heart and kidney failures compared with younger patients. They also have non-specific neurologic symptoms leading to a delayed diagnosis. Factors influencing this impaired survival among olderpatients remain unknown so far. Alteration of the functional capacity of involved organs could be part ofthe explanation as could be the consequences of vascular aging. In fact, severe ADAMTS13 deficiency isnecessary but likely not sufficient for iTTP physiopathology. A second hit leading to endothelial activationis thought to play a central role in iTTP. Interestingly, the mechanisms involved in endothelial activationmay share common features with those involved in vascular aging, potentially leading to endothelialdysfunction. It could thus be interesting to better investigate the causes of mid- and long-term mortalityamong older iTTP patients to confirm whether inflammation and endothelial activation really impactvascular aging and long-term mortality in those patients, in addition to their presumed role at iTTP acutephase. If so, further insights into the mechanisms involved could lead to new therapeutic targets. (C) 2021 Societe Nationale Francaise de Medecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.