CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility

Abstract

Background: ABO antigens are expressed on the surfaces of red blood cells and the vascular endothelium. We studied circulating endothelial microparticles (EMP) in ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial activation to test a hypothesis of possible endothelial injury in neonates with ABO HDN, and its relation with the occurrence and severity of haemolysis.

Material and methods: Forty-five neonates with ABO HDN were compared with 20 neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy neonates with matched mother and infant blood groups (healthy controls). Laboratory investigations were done for markers of haemolysis and von Willebrand factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after therapy (exchange transfusion and/or phototherapy).

Results: vWF Ag and pre-therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy controls, and were significantly higher in babies with ABO HDN than in those with Rh HDN (p<0.05). In ABO HDN, pre-therapy EMP levels were higher in patients with severe hyperbilirubinaemia than in those with mild and moderate disease or those with Rh HDN (p<0.001). Post-therapy EMP levels were lower than pre-therapy levels in both the ABO HDN and Rh HDN groups; however, the decline in EMP levels was particularly evident after exchange transfusion in ABO neonates with severe hyperbilirubinaemia (p<0.001). Multiple regression analysis revealed that the concentrations of haemoglobin, lactate dehydrogenase and indirect bilirubin were independently correlated with pre-therapy EMP levels in ABO HDN.

Discussion: Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury parallel to the IgG-mediated erythrocyte destruction and could serve as a surrogate marker of vascular dysfunction and disease severity in neonates with this condition.

Figure 1

Flow cytometric analysis of endothelial microparticles (EMPs). The left box shows gating of platelets region by forward scatter (FS) and side scatter (SS). The right box shows identification of CD144+ EMPs by FS as a percentage of CD144+ positive events.

Figure 2

Level of endothelial microparticles in the three groups studied. EMP: endothelial microparticles; HDN: haemolytic disease of the newborn.

Figure 3

Level of endothelial microparticles in the three subgroups of neonates with ABO HDN. HDN: haemolytic disease of the newborn.

Figure 4

Significant correlations between pre-therapy level of endothelial microparticles (EMP) and laboratory variables in neonates with ABO HDN (group I). HDN: haemolytic disease of the newborn.