A-153 Association Between Intracellular Creatine Concentration in Erythrocytes and Reticulocyte Granularity Distribution as a Novel Indicator of Hematopoietic Activity

Abstract Background In recent years, the measurement of intracellular creatine (EC) concentration in erythrocytes has attracted attention as an alternative to the conventional 51Cr labeling method for assessing erythrocyte lifespan. EC concentration has been considered useful for the early diagnosis of intravascular hemolysis and the evaluation of hematopoietic function. However, our study revealed a negative correlation between EC concentration and hemoglobin levels, suggesting that EC concentration may serve as an indicator of hematopoietic activity rather than erythrocyte lifespan. Aim This study aimed to elucidate the relationship between EC concentration and hematological parameters, including reticulocyte granularity, to assess its potential as a novel indicator of hematopoietic activity. Methods A total of 314 patients (186 males and 128 females) aged 18 to 93 years at Kawasaki Medical School Hospital were included in this study. EC concentration was measured, and hematological test results, including reticulocyte scattergram patterns, were extracted to construct a database. Based on EC concentration, males with =5.06 mg/dL and females with =5.76 mg/dL were classified as the EChyper group, while males with <1.87 mg/dL and females with <2.31 mg/dL were classified as the EChypo group. The crude odds ratio [95% confidence interval] for the EChyper group was calculated to identify hematological parameters associated with EC concentration. Additionally, flow cytometry standard (FCS) format data of hematological measurements were compressed into 1024 parameters, followed by self-organizing map (SOM) analysis to cluster granulometric patterns. The correlation between EC concentration and reticulocyte distribution was also visualized. Results In the EChyper group, crude ORs were high for the percentage of nucleated red blood cells (52.2 [26.6-116]), the percentage of fragmented red blood cells (2.37 [1.70-3.53]), and red blood cell distribution width (2.02 [1.79-2.30]). Conversely, ORs were low for red blood cell count (0.60 [0.47-0.85]) and hemoglobin concentration (0.68 [0.63-0.73]). SOM analysis demonstrated that higher EC concentrations were associated with an increased proportion of microcytic erythrocytes, particularly immature nucleated erythrocytes. Additionally, a strong correlation with erythropoietin levels was observed. Discussion Elevated EC concentrations were found in cases with increased microcytic and fragmented erythrocytes, such as iron deficiency anemia, where erythrocyte size variation was pronounced. These findings suggest that EC concentration serves as a more relevant indicator of hematopoietic activity rather than erythrocyte lifespan. Conclusion EC concentration is a promising marker for evaluating hematopoietic activity, including hemoglobin synthesis, rather than erythrocyte lifespan. It may also have potential applications as a marker for erythropoietin activity.