Normal saline is associated with increased sickle red cell stiffness and prolonged transit times in a microfluidic model of the capillary system

• Published in: Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2017-07, Vol.24 (5), p.n/a
• Main Authors: Carden, Marcus A., Fay, Meredith, Sakurai, Yumiko, McFarland, Brynn, Blanche, Sydney, DiPrete, Caleb, Joiner, Clinton H., Sulchek, Todd, Lam, Wilbur A.
• Format: Article
• Language: English
• Subjects: Anemia, Sickle Cell - blood; Anemia, Sickle Cell - complications; atomic force microscopy; Biomechanics; Capillaries - physiopathology; cellular mechanics; Erythrocytes; Erythrocytes - drug effects; Erythrocytes - pathology; Humans; intravenous fluids; microfluidics; Microfluidics - methods; Microscopy, Atomic Force; Models, Cardiovascular; sickle‐cell disease; Sodium Chloride - adverse effects; Sodium Chloride - pharmacology; Vascular Diseases - chemically induced; vaso‐occlusion
• ISSN: 1073-9688; 1549-8719
• DOI: 10.1111/micc.12353

Objective 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. Methods 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. Results Sickle RBCs exposed to normal saline (NS) had increased stiffness, TTs, and propensity to microchannel occlusion compared to other osmolarities. Conclusion 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.