A study for red blood cell as physiological marker

Abstract

Red blood cell (RBC) is a basic human blood cell and related blood tests are performed in a clinic. But the study with clinical implications for RBC is limited. This dissertation aims to discover a novel and clinically meaningful maker for RBC via biomedical engineering with a translational approach. In chapter 2, hemoglobin variability was evaluated as a clinical predictive marker for clinical outcomes, including mortality and development of hypertension. In Korea, abnormal hemoglobin level is checked annually by national health screening program. However, hemoglobin level in individuals is inconstant and hemoglobin changes are affected by various clinical conditions. Therefore, the association between hemoglobin variability and clinical outcomes was investigated using a cohort from the National Health Insurance Service-Health Screening database. In summary, hemoglobin variability is associated with clinical outcomes in multiple settings of analyses including sensitivity and subgroup analyses. In chapter 3, RBC physical index was evaluated as a hemorheological marker for evaluating the effect of anti-diabetic medication in diabetic patients. Sodium-glucose cotransporter 2 (SGLT-2) inhibitor is an anti-diabetic drug that improves cardiovascular outcomes. Generally, hematocrit level increases after SGLT-2 inhibitor administration. Although elevated hematocrit increases blood viscosity and risk of cardiovascular disease, SGLT-2 inhibitor has protective effects on the cardiovascular system. A mechanism for this paradoxical phenomenon remains unclear. Furthermore, the effect of SGLT-2 inhibitor on hemorheology has not been studied. Therefore, hemorheological parameters of diabetic patients were evaluated. In summary, RBC deformability was improved in the SGLT-2 inhibitor group compared with that in the control drug group. This improvement is supposed to have a protective effect on the cardiovascular system. In chapter 4, RBC shape was evaluated as a morphological marker for response to change of solution osmolality. Phosphate-buffered saline (PBS) and Alsever's solution (AS) are frequently used as media in blood-related studies. Despite frequent use, the effect of these solutions on RBC shape has not been studied. Blood from five healthy subjects was used in this study. RBC shape change caused by osmolality and solute was evaluated using three-dimensional refractive index tomography. In summary, sodium chloride alone cannot elicit the biconcave shape of RBC, which can maintain only in the presence of an osmotic pressure-maintaining substance, such as glucose or mannitol. Through three chapters, three RBC makers were proposed: 1) hemoglobin variability can be a marker for clinical outcome. 2) RBC deformability can be a marker for the effect of specific medication. 3) RBC morphology can be a marker for osmolality and solute of solution. Overall, these novel markers are applicable for clinics and could predict patient outcomes.