Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical: Poster I
Hematology Disease Topics & Pathways:
Adult, Diseases, sickle cell disease, cellular interactions, Biological Processes, Pediatric, Technology and Procedures, Hemoglobinopathies, Study Population, Clinically relevant
We developed a standardized, flow-based adhesion assay to measure p-selectin mediated adhesion in SCD. Whole blood (Wb) and isolated WBC samples were perfused (1.0 dynes/cm2, 1.67Hz) through micro-fluidic channels. Adhered cells were enumerated and an adhesion index was calculated (total # of adhered cells/mm2). Blood samples were collected from SCD subjects (n = 35) every 3 weeks for 6 months at baseline and within 24 and 48hrs of a patient-reported VOE. Baseline and VOE states were confirmed by an electronic patient reported outcomes (ePRO) device, as previously described. VOEs were separated into 2 groups: VOEs managed at-home (Home-VOE) or during ER visit and/or hospitalization (Contact-VOE).
WB (n = 288; mean=42 ± 48 cells/mm2, median=31 cells/mm2) and WBC (n = 282; mean=163 ± 149 cells/mm2; median= 116 cells/mm2) adhesion to p-selectin varied in SCD subjects (n=35) at baseline. WBC adhesion to P-selectin was significantly (p=0.36) higher during VOE (n=59; 205 ± 179) when compared to baseline (n = 282; mean=163±149 cells/mm2, median=116 cells/mm2). For individual subjects, the geometric mean for WBC adhesion to P-selectin was significantly (p = 0.023) higher for VOEs vs. baseline (VOE= 109, n= 23, 95% confidence interval 94-126 vs. baseline= 148, n = 35, 95% confidence interval 114-192). Additionally, WB adhesion to p-selectin correlated with VOE frequency (time to 2ndVOE; r = -0.71, n = 10, p = 0.02 or time between 1stand 2ndVOEs; r = -0.68, n = 10, p = 0.032).
WB adhesion to p-selectin positively correlated with C-reactive protein (CRP; r = 0.12, p = 0.047), reticulocyte % (r = 0.15, p = 0.017), and WBC counts (r = 0.26, p < 0.0001) at baseline. WBC adhesion to p-selectin positively correlated with hematocrit (Hct; r = -0.37, p = 0.027) and reticulocyte % (r = 0.44, p = 0.0058) during VOEs managed at home; WB adhesion to p-selectin positively correlates with CRP (r = 0.44, p = 0.011) and WBC count (r = 0.63, p < 0.0001); WB adhesion to p-selectin positively correlated with WBC count (r = 0.51, p = 0.0021) during contact-VOE.
These data confirm the normal range and longitudinal variability of SCD adhesion to p-selectin at baseline and during VOEs. WB adhesion to p-selectin was inversely related to VOE frequency although there was no difference between baseline and VOE samples. These data suggest that WB adhesion to p-selectin may be a better predictor of disease severity and not SCD symptomology. In contrast, WBC adhesion to p-selectin differentiated baseline from VOE samples suggesting this assay may be a more suitable reflection of SCD clinical state. Both WB and WBC adhesion to VCAM-1 correlates with biomarkers of hemolysis and inflammation. P-selectin may be selective for the identification of pro-adhesive phenotypes directly related to hemolytic and inflammatory influencers in SCD.
Disclosures: Liu: Functional Fluidics: Equity Ownership. Gao: Functional Fluidics: Equity Ownership. White: functional fluidics: Equity Ownership. Callaghan: Alnylam Pharmaceuticals: Equity Ownership; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Employment, Membership on an entity's Board of Directors or advisory committees; Hema Pharmaceuticals: Honoraria; Grifols: Honoraria; Sancilio Pharmaceuticals Company: Employment; Global Blood Therepeutics: Employment; Roche/Genentech: Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria; Octapharma: Honoraria; Pfizer: Employment, Honoraria, Research Funding; Amgen: Employment. Hines: functional fluidics: Equity Ownership.
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