Exploring the Interplay between Donor Sex, CD71+ RBCs, Erythrophagocytosis and Hospital-onset Sepsis

• Author / Creator

  Li, Wenhui

• Transfusion of red cell concentrates (RCCs) is common for treating anemia in Intensive care unit (ICU) patients, but it may result in adverse outcomes like sepsis, potentially due to donor sex-related immune responses. CD71+ RBCs, which are immature, may influence erythrophagocytosis, where the monocyte system removes damaged or aged RBCs—a process that could lead to complications if overwhelmed.
  The hypothesis posits that the number of CD71+ RBCs in blood products was affected by donor sex and the donor factors can predict post-transfusion hemoglobin levels and the rate of hospital-onset sepsis. Flow cytometry quantified CD71+ RBCs, revealing that levels are generally higher in male donors, are affected by processing methods, and decrease with storage time. A positive correlation between CD71+ RBCs and hemoglobin levels was noted.
  In vitro experiments demonstrated that higher proportion of CD71+ RBCs were associated an increase in the phagocytosis index (PI) of RBCs, elevated supernatant Hb, and loss of CD14+ monocytes. The increase in PI and decrease in CD14+ monocytes could be reversed after CD71+ RBCs were treated with a reactive oxygen species (ROS) inhibitor. This suggests that CD71+ RBCs with high ROS level may exhibit an immunomodulatory role during in vitro erythrophagocytosis. Dose-dependent relationships were also observed between the PI of CD71+ RBCs and the proportion of CD71+ RBCs, as well as between supernatant Hb and the proportion of CD71+ RBCs.
  Retrospective analysis showed no significant link between donor sex and hospital-onset sepsis. However, blood from male donors resulted in higher hemoglobin increments, notably in female recipients. Factors like recipient age and the number of transfused RCC units were significant for sepsis, while the donor's hemoglobin level influenced the hemoglobin increment in the recipients.
  This study underscores the need for further in vivo research to clarify the impact of donor sex on CD71+ RBCs and transfusion outcomes. It provides an immune perspective on donor sex-related mechanisms in transfusion responses. The findings suggest that both donor and recipient factors should be considered to optimize transfusion practices, as the data points to the potential of including CD71+ RBCs as a factor in managing transfusion-related immunomodulation in ICU settings.

• Subjects / Keywords

  • Donor sex
  • young RBCs
  • RBC clearance
  • Sepsis
  • Intensive care unit

• Graduation date

  Spring 2024

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-84ye-7791

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.