Figure 5. Red blood cell mediated microcapillary occlusion in vitro and the resultant Occlusion Index (OI) associate with fetal hemoglobin level (HbF%) in subjects with sickle cell disease (SCD).

(A) HbF% has been shown to associate with improved clinical outcomes in SCD, where HbF>8.6% is considered as a therapeutic threshold. OI associates with blood HbF level in SCD, where subjects with higher HbF levels (HbF>8.6%) displayed significantly lower OIs (mean ± SEM = 0.88% ± 0.10%, N=6), compared with those with lower HbF levels (HbF≤8.6%) (mean ± SEM = 3.18% ± 0.34%, N=10, p<0.001, one-way ANOVA). Error bars represent standard error of the mean (SEM). (B) Hydroxyurea therapy is known to improve RBC deformability and to increase HbF% in some but not all patients with SCD. Among the 11 subjects tested who were on Hydroxyurea therapy (circles), 5 subjects presented lower HbF levels (HbF≤8.6%) and higher OIs (red circles), while the other 6 subjects presented higher HbF levels (HbF>8.6%) and lower OIs (black circles). All 5 subjects on Transfusion therapy displayed HbF levels less than 8.6% and higher OIs (red triangles) compared with subjects who were on Hydroxyurea with HbF greater than 8.6%. These results suggest that OI would be useful in assessing the clinical outcomes and treatment efficacy in SCD, along with other important clinical parameters, such as HbF%.