We did not observe increases in the rates of vaso-occlusive crises, given as median (range), with ESA only [2/year (0 – 7/year) vs. 2/year (0 – 6/year)], newly prescribed HC-only [2/year (0 – 11/year) vs. 2/year 0 – 10/year)], newly prescribed HC+ESA [1/year (0 – 9/year) vs. 1/year (0 – 7/year)] or stable HC+ESA [1/year (0 – 11/year) vs. 0/year (0 – 8/year)] from the year pre-ESA when compared to the year of ESA therapy, respectively.