CIRCULATING ACTIVATED ENDOTHELIAL-CELLS IN SICKLE-CELL-ANEMIA

Background The vascular wall participates in the pathogenesis of sickl e cell disease. To determine whether the endothelium is activated in t his disease, we studied the number, origin, and surface phenotype of c irculating endothelial cells in patients with sickle cell anemia. Meth ods We used immunohistochemical examination of buffy-coat smears to en umerate circulating endothelial cells, and we evaluated the surface ph enotype by applying immunofluorescence microscopy to preparations of c irculating endothelial cells. A panel of antibodies was used, includin g a specific anti-endothelial-cell antibody, P1H12. Results Mean (+/-S D) numbers of circulating endothelial cells in normal blood donors, pa tients with sickle cell trait, and patients with hemolytic anemias not due to hemoglobin S were 2.6+/-1.6, 3.0+/-2.6, and 2.0+/-0.8 per mill iliter of whole blood, respectively. Patients with sickle cell anemia who presented with acute painful episodes had 22.8+/-18.2 circulating endothelial cells per milliliter of blood (P<0.001 for the comparison with normal donors), and patients with no such events within one month before or after blood sampling had 13.2+/-11.8 circulating endothelia l cells per milliliter of blood (P=0.002 for the comparison with norma l donors and P=0.019 for the comparison with patients with acute event s). Serial observations of three patients showed a tendency toward hig her levels of circulating endothelial cells at the onset of acute pain ful crises. The average viability of circulating endothelial cells was 66+/-30 percent. In patients with sickle cell anemia, regardless of c linical status, the circulating endothelial cells were predominantly m icrovascular in origin (CD36-positive), and most of the cells expresse d four markers of endothelial-cell activation: intercellular adhesion molecule 1, vascular-cell adhesion molecule 1, E-selectin, and P-selec tin. Conclusions Our studies suggest that the vascular endothelium is activated in patients with sickle cell anemia, regardless of the patie nts' clinical status. Adhesion proteins on activated endothelial cells may have a role in the vascular pathology of sickle cell disease. (C) 1997, Massachusetts Medical Society.