Use of the microfluidic impedance red cell assay in sickle cell disease

Abstract

In sickle cell disease (SCD), red blood cells (RBCs) are poorly deformable, even under normoxia (NOI). With deoxygenation, deformability of sickle RBCs is further reduced due to polymerization of hemoglobin S (HbS). Rigid, poorly deformable sickle RBCs block microvasculature, causing ischemia, pain, and organ damage. The microfluidic impedance red cell assay (MIRCA) can mechanically measure RBC deformability, providing occlusion index under NOI or hypoxia (HOI) as readouts. We analyzed RBCs from 68 adult and 34 pediatric patients with SCD using the MIRCA. Higher HOI and NOI values were positively associated with markers of inflammation, hemolysis, RBC density, older age, and severe SCD genotypes (homozygous HbSS or HbS β0-thalassemia. Each 1% higher NOI across individuals was associated with a 6.3% higher incidence of acute complications per year. Individuals with chronic complications in the past year had a 3.1% higher median NOI than those without chronic complications. Individuals on chronic transfusion therapy exhibit a subpopulation of poorly deformable RBCs captured by the MIRCA but not by a commercially available device that also measures RBC deformability, the laser assisted optical rotational cell analyzer (LoRRca). In vitro addition of voxelotor or osivelotor to samples from individuals on chronic transfusion therapy improved the deformability of these endogenous RBCs. Longitudinally collected NOI and HOI values in individuals with HbSS were stable, with a median percent point change of 13.3% and 15.7%, respectively. MIRCA can be used in combination with clinical laboratory tests to monitor RBC deformability as a biomarker of clinical status at routine clinic visits and included in clinical trials of disease-modifying agents.