title: Normal saline is associated with increased sickle red cell stiffness and prolonged transit times in a microfluidic model of the capillary system.
abstract: Vaso-occlusive crisis (VOC) is a complex process that occurs in patients with sickle cell disease (SCD) and is often associated with pain and urgent hospitalization. A major instigator of VOC is microvascular obstruction by pathologically stiffened sickle red blood cells (RBCs), and thus, therapy relies heavily on optimizing intravenous fluid (IVF) hydration to increase RBC deformability. However, no evidence-based guidelines regarding the choice of IVF currently exist. We therefore analyzed alterations in biomechanical properties of sickle RBCs isolated from patients with homozygous SCD (hemoglobin SS) after exposure to different osmolarities of clinical IVF formulations.
  
  
  
  Atomic force microscopy (AFM) was used to assess stiffness of RBCs after exposure to different IVFs. A microfluidic model of the human capillary system was used to assess transit time (TT) and propensity to occlusion after exposure to the different IVF formulations.
  
  
  
  Sickle RBCs exposed to normal saline (NS) had increased stiffness, TTs, and propensity to microchannel occlusion compared to other osmolarities.
  
  
  
  NS, an IVF formulation often used to treat patients with SCD during VOC, may induce localized microvascular obstruction due to alterations of sickle RBC biomechanical properties.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.|The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.
authors.forename: Marcus A
authors.identifier: 0000-0003-3860-3619
authors.initials: MA
authors.lastname: Carden
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.|The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.|Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.|Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Fay
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.|The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.|Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.|Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Georgia Tech School of Chemical & Biomolecular Engineering, Atlanta, GA, USA.
authors.forename: Brynn
authors.initials: B
authors.lastname: McFarland
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.
authors.forename: Sydney
authors.initials: S
authors.lastname: Blanche
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.
authors.forename: Caleb
authors.initials: C
authors.lastname: DiPrete
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Clinton H
authors.initials: CH
authors.lastname: Joiner
authors.affiliation: Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.|George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Sulchek
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.|The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.|Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.|Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Lam
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications; D002196:Capillaries / Q000503:physiopathology*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D044085:Microfluidics / Q000379:methods; D018625:Microscopy, Atomic Force; D008955:Models, Cardiovascular; D012965:Sodium Chloride / Q000009:adverse effects* / Q000494:pharmacology; D014652:Vascular Diseases / Q000139:chemically induced
chemical_list: D012965:Sodium Chloride
keywords: atomic force microscopy; cellular mechanics; intravenous fluids; microfluidics; sickle-cell disease; vaso-occlusion