Marcus A Carden1,2, Meredith Fay1,2,3,4, Yumiko Sakurai1,2,3,4, Brynn McFarland5, Sydney Blanche2, Caleb DiPrete2, Clinton H Joiner1, Todd Sulchek3,6, Wilbur A Lam1,2,3,4. 1. 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. 2. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA. 3. Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA. 4. Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA. 5. Georgia Tech School of Chemical & Biomolecular Engineering, Atlanta, GA, USA. 6. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Abstract
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.
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.
Authors: Marcus A Carden; David C Brousseau; Fahd A Ahmad; Jonathan Bennett; Seema Bhatt; Amanda Bogie; Kathleen Brown; Theron Charles Casper; Laura L Chapman; Corrie E Chumpitazi; Daniel Cohen; Carlton Dampier; Angela M Ellison; Hartmut Grasemann; Robert W Hickey; Lewis L Hsu; Sara Leibovich; Elizabeth Powell; Rachel Richards; Syana Sarnaik; Debra L Weiner; Claudia R Morris Journal: Am J Hematol Date: 2019-04-29 Impact factor: 10.047
Authors: Marcus A Carden; Meredith E Fay; Xinran Lu; Robert G Mannino; Yumiko Sakurai; Jordan C Ciciliano; Caroline E Hansen; Satheesh Chonat; Clinton H Joiner; David K Wood; Wilbur A Lam Journal: Blood Date: 2017-10-04 Impact factor: 25.476
Authors: Aafke E Gaartman; Ajab K Sayedi; Jorn J Gerritsma; Tim R de Back; Charlotte F van Tuijn; Man Wai Tang; Harriët Heijboer; Koen de Heer; Bart J Biemond; Erfan Nur Journal: Br J Haematol Date: 2021-07-15 Impact factor: 6.998