Is Endothelial Activation a Critical Event in Thrombotic Thrombocytopenic Purpura?

Raphael Cauchois (1, 2) , Romain Muller (1, 2) , Marie Lagarde (1, 3) , Françoise Dignat-George (1, 4) , Edwige Tellier (1, 5) , Gilles Kaplanski (1, 2)

1 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
2 Service de médecine interne et immunologie clinique, AP-HM, Marseille
3 CNR-MAT - Centre national de référence des microangiopathies thrombotiques
4 Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM]
5 CNR-MAT - Centre national de référence des microangiopathies

Thrombotic thrombocytopenic purpura (TTP) is a severe thrombotic microangiopathy. The current pathophysiologic paradigm suggests that the ADAMTS13 deficiency leads to Ultra Large-Von Willebrand Factor multimers accumulation with generation of disseminated microthrombi. Nevertheless, the role of endothelial cells in this pathology remains an issue. In this review, we discuss the various clinical, in vitro and in vivo experimental data that support the important role of the endothelium in this pathology, suggesting that ADAMTS13 deficiency may be a necessary but not sufficient condition to induce TTP. The "second hit" model suggests that in TTP, in addition to ADAMTS13 deficiency, endogenous or exogenous factors induce endothelial activation affecting mainly microvascular cells. This leads to Weibel-Palade bodies degranulation, resulting in UL-VWF accumulation in microcirculation. This endothelial activation seems to be worsened by various amplification loops, such as the complement system, nucleosomes and free heme.

Mots clés: endothelial cells; Weibel-Palade bodies; Thrombotic thrombocytopenic purpura

Domaines: Sciences du Vivant [q-bio]

Raphael Cauchois, Romain Muller, Marie Lagarde, Françoise Dignat-George, Edwige Tellier, et al.. Is Endothelial Activation a Critical Event in Thrombotic Thrombocytopenic Purpura?. Journal of Clinical Medicine, 2023, 12 (3), pp.758. ⟨10.3390/jcm12030758⟩. ⟨hal-04017464⟩