Michael J Simmonds1, Silvie Suriany2, Derek Ponce3, Jon A Detterich3,4. 1. Menzies Health Institute Queensland, Griffith University, Queensland, Australia. 2. Division of Hematology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA. 3. Division of Cardiology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA. 4. Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Abstract
BACKGROUND: Sickle cell disease (SCD) is a genetically inherited hemoglobinopathy in which deoxygenated hemoglobin S polymerizes, leading to stiff red blood cells (RBCs) and inefficient microcirculatory blood flow. Transfusion therapy acts as primary and secondary prevention of ischemic stroke in SCD. Whether blood transfusion alters the mechanical sensitivity (MS) of RBCs to prolonged subhemolytic shear stress (shear) is unknown. We hypothesized that individuals with SCD undergoing chronic blood transfusion would have improved sensitivity to shear, compared with patients not undergoing transfusion therapy. STUDY DESIGN AND METHODS: Blood suspensions from individuals with SCD not receiving (n = 15) and receiving (n = 15) chronic simple transfusion were conditioned to shear (1, 4, 16, 32, and 64 Pa) for various durations (1, 4, 16, 32, and 64 sec), and then deformability of RBCs was immediately measured. Healthy young controls (n = 15) were included for reference. A surface mesh was interpolated using the data to determine the effect of blood transfusion on MS of RBCs. RESULTS: There was impaired RBC deformability to prolonged supraphysiologic shear in both SCD groups; however, MS improved in transfused patients when exposed to prolonged physiologic shear. Furthermore, in the transfused patients with SCD, the threshold above which subhemolytic damage occurs was similar to controls. CONCLUSION: We found that chronic transfusion therapy normalizes the MS threshold above which RBC subhemolytic damage occurs after prolonged shear exposure in SCD. An important and novel finding in transfused patients with SCD was the improvement in RBC deformability in response to prolonged shear exposure over the physiologic range.
BACKGROUND:Sickle cell disease (SCD) is a genetically inherited hemoglobinopathy in which deoxygenated hemoglobin S polymerizes, leading to stiff red blood cells (RBCs) and inefficient microcirculatory blood flow. Transfusion therapy acts as primary and secondary prevention of ischemic stroke in SCD. Whether blood transfusion alters the mechanical sensitivity (MS) of RBCs to prolonged subhemolytic shear stress (shear) is unknown. We hypothesized that individuals with SCD undergoing chronic blood transfusion would have improved sensitivity to shear, compared with patients not undergoing transfusion therapy. STUDY DESIGN AND METHODS: Blood suspensions from individuals with SCD not receiving (n = 15) and receiving (n = 15) chronic simple transfusion were conditioned to shear (1, 4, 16, 32, and 64 Pa) for various durations (1, 4, 16, 32, and 64 sec), and then deformability of RBCs was immediately measured. Healthy young controls (n = 15) were included for reference. A surface mesh was interpolated using the data to determine the effect of blood transfusion on MS of RBCs. RESULTS: There was impaired RBC deformability to prolonged supraphysiologic shear in both SCD groups; however, MS improved in transfused patients when exposed to prolonged physiologic shear. Furthermore, in the transfused patients with SCD, the threshold above which subhemolytic damage occurs was similar to controls. CONCLUSION: We found that chronic transfusion therapy normalizes the MS threshold above which RBC subhemolytic damage occurs after prolonged shear exposure in SCD. An important and novel finding in transfused patients with SCD was the improvement in RBC deformability in response to prolonged shear exposure over the physiologic range.
Authors: M A Pelidis; G J Kato; L M Resar; G J Dover; D G Nichols; L K Walker; J F Casella Journal: J Pediatr Hematol Oncol Date: 1997 Sep-Oct Impact factor: 1.289
Authors: Marijke Grau; Sebastian Pauly; Jamal Ali; Katja Walpurgis; Mario Thevis; Wilhelm Bloch; Frank Suhr Journal: PLoS One Date: 2013-02-12 Impact factor: 3.240