A Longitudinal Study to Identify and Assess Adhesion Indices during Vaso-Occlusive Crises in Adults and Adolescents with Sickle Cell Disease

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.1097-1097
• Main Authors: White, Jennell, Gao, Xiufeng, Liu, Ke, Callaghan, Michael U., Hines, Patrick C.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-120311

Sickle cell disease (SCD) is characterized by frequent and unpredictable vaso-occlusive complications (VOCs); however, there are no objective measures for VOC as a clinical endpoint. Vaso-occlusion results from processes that reduce blood flow in the microvasculature, including red cell stickiness and erythrocyte sickling. These processes lead to pain, chronic organ damage, and decreased life expectancy. The decision to seek medical contact varies amongst patients. When VOCs are managed at home valuable information remains unknown. We designed a longitudinal, observational study to capture adhesion data at home and in a hospital setting. The objective of this study was to determine whether a standardized, flow-based adhesion bioassay is capable of identifying VOCs occurring in SCD patients with varying degrees of medical contact. SCD patients (n=33) were evaluated over a 6-month period. Blood samples were collected every 3 weeks; when patients report a VOC corresponding blood samples are collected and steady state samples are resumed. During 6 months of evaluation, longitudinal measures of pain and clinical laboratory and biomarker samples from SCD patients (+/- hydroxyurea therapy) in steady state to VOC were studied. Blood samples were collected in sodium citrate from SCD subjects at steady state and during VOCs. Blood samples were perfused through VCAM-1-coated microchannels at standard physiologic flow conditions (1dyne/cm2, 1.67Hz). An adhesion index was established by quantifying adherent cells within a standard viewing area (cells/mm2), and could be obtained within 6-9 min. Adhesion indices varied from sample-to-sample at baseline (n=289; mean = 355 ± 235; median = 297 cells/mm2) and during VOC (n=59, mean=416±233, median=390). Repeated measures of adhesion over 6 months reveals significant intra-patient associations with C-reactive protein (CRP, n=335, r=0.16; p=0.006), lactose dehydrogenase (LDH, n=336, r=0.12; p=0.032), white blood cells (WBC, n=341, r=0.13; p=0.019), and reticulocyte percent (n=336, r=0.37, p