Beyond the Blood Cell: The Emerging Role of Cell-Free DNA in Transfusion Medicine

Jackson M Wahman1, Rhoda X Hijazi1, Elizabeth Duncan1

  • 1Department of Physiology and Pharmacology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX, USA.

Journal of Hematology
|September 4, 2025
PubMed

Insights

Cell-free DNA (cfDNA) from transfusions can persist in recipients, potentially causing immune reactions and genomic changes. Current blood processing does not remove cfDNA, necessitating improved safety measures for transfusions.

Area of Science:

  • * Transfusion Medicine
  • * Molecular Biology
  • * Immunology

Background:

  • * Cell-free DNA (cfDNA) is fragmented DNA in circulation, crucial for diagnostics.
  • * cfDNA in transfused blood products presents new clinical challenges.
  • * Donor cfDNA can lead to transfusion-associated microchimerism in recipients.

Purpose of the Study:

  • * To review the persistence and immunologic impact of donor cfDNA in transfusion recipients.
  • * To examine the potential for cfDNA genomic integration and immune pathway activation.
  • * To highlight the limitations of current leukoreduction in cfDNA removal.

Main Methods:

  • * Synthesis of current scientific literature on cfDNA in transfusion.
  • * Analysis of evidence regarding cfDNA persistence, integration, and immune effects.
  • * Evaluation of existing blood processing techniques, including leukoreduction.

Main Results:

  • * Donor cfDNA can persist long-term in transfusion recipients.
  • * cfDNA may integrate into the host genome and alter epigenetic modifications.
  • * Innate immune pathways, like Toll-like receptors, can be activated by cfDNA.
  • * Environmental or dietary DNA in transfused cfDNA may influence immune regulation.
  • * Leukoreduction does not eliminate cfDNA or prevent microchimerism.

Conclusions:

  • * Donor cfDNA poses potential risks including immune activation and genomic alterations.
  • * Current blood processing methods are insufficient to mitigate cfDNA-related risks.
  • * Further research and improved blood processing are essential for transfusion safety.

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