So far, early hemorrhagic death remains a major obstacle to complete remission in acute promyelocytic leukemia (APL). The number of leukemia cells in the blood is a better predictor of bleeding events than other hematological parameters.
Vascular endothelial homeostasis is associated with spontaneous bleeding. In APL, how APL cells interact with vascular endothelial cells and whether this interaction affects bleeding complications remains unknown.
In this study, APL cells induced endothelial cell (EC) contraction
and pore formation, resulting in endothelial hyperpermeability
in vitro and hemorrhage in vivo.
Asiatic acid, extracted from a Chinese herb, anti-ICAM1, and anti-VCAM1 antibodies blocked leukemic cells from activating ECs and alleviated the bleeding in APL mice models. ECs stimulated by APL cells converted to procoagulant phenotype through phosphatidylserine exposure.
Intercellular fibrin networks generated along the edge of the
retracted ECs sealed the barrier injury and reduced the permeability of endothelial monolayers to RBCs. In addition, all-trans
retinoic acid rescued the morphological alterations of ECs that
occurred in the process of exposure to NB4 cells.
Endothelial integrity plays a key role in preventing bleeding
complications in APL. Blocking leukemic cell adhesion to the
vascular wall and regulating endothelium homeostasis may
provide novel potential therapeutic targets for intervention in
hemorrhage of APL. In addition, reassessment of the target level
of transfused Fbg according to different risk stratifications may
also be necessary.
This paper opens a window on disregulated endothelial homeostasis in severe Covid-19, where the neutrophil proteases and NETs release induce endothelial damage with hyperpermeability and the fibrin intercellular network is disturbed.