The 'scintilla' starting vaso-occlusion in sickle cell disease.

Abstract

RBCEV SS RBC SS Reduced adhesion to endothelial cells# RBCEV AA RBC AA ADAMTS-13 is a metalloproteinase that cleaves von vWF and ultra large vWF. The importance of ADAMTS-13 is well known for conditions where vaso-occlusion occurs in microvessels, such as in thrombotic thrombocytopenic purpura (TTP). Similarly to hemopexin, the demonstration of a direct involvement of ADAMTS-13 in the adhesion process of SCD is relevant for potential therapeutical development. In fact, An Ran et al. showed that in the presence of hemopexin and ADAMTS-13, adhesion of sickle erythrocytes is returned to the level seen when normal erythrocytes are tested. The finding of an involvement of vWF in sickle cell adhesion suggests a role for anticoagulant proteins in SCD. This is also in keeping with similar findings of reduced naturally occurring anticoagulant (Protein C and Protein S) and vaso-occlusion in SCD.2, 10 In our opinion, this study has a strong scientific value, since it has been conducted in both in vitro and in vivo studies, in a mouse model with SCD. It will now be important to validate these findings in human trials, possibly in a large cohort of patients with SCD. If these findings were to be further corroborated, RBCEVs could potentially be used as a new parameter for monitoring SCD patients in a steady state and during SCD crises. RBCEV trials may possibly even predict SCD crises. Finally, the link between RBCEV, hemopexin and ADAMTS-13 offer an excellent target for the development of future treatment strategies for SCD.