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Role of thrombocytopenia in radiation-induced mortality and review of therapeutic approaches targeting platelet regeneration after radiation exposure

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  • Published:
Journal of Radiation Oncology

Abstract

Background

Preclinical studies on irradiated animals show that thrombocytopenia can play a role in radiation mortality, particularly in animals receiving minimal supportive care. These findings are consistent with anecdotal evidence from the atomic bombings, where bleeding complications were noted often in patients.

Objective

To evaluate the role of thrombocytopenia and hemorrhage in radiation-induced mortality, a review was conducted of publicly available pathology reports of patients who died following radiation exposure. Of the 42 reports identified with reasonably complete information, exposures resulted from nuclear detonation, contact with improperly disposed sources, radiotherapy, or industrial accidents.

Results

Consistent with animal data, a high incidence of bleeding was noted in the autopsy reports of the victims. Also presented is a review of animal model data on the use of various forms of thrombopoietin (TPO) as a treatment for hematopoietic acute radiation syndrome (ARS). Although animal studies suggested these approaches would increase platelet levels following lethal irradiation, their clinical development was halted due to lack of significant efficacy for chemotherapy-induced thrombocytopenia and safety concerns.

Conclusion

Because there is currently no approved treatment stockpiled for radiation-induced thrombocytopenia, second-generation TPO mimetics and other novel platelet-promoting agents should be developed for this indication.

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Acknowledgments

The authors wish to thank the program staff within the NIAID Radiation Nuclear Countermeasures Program, including Dr. David Cassatt and Dr. Francesca Macchiarini, as well as Dr. Thomas MacVittie (University of Maryland School of Medicine) for their critical review of the manuscript.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Radiation/Nuclear Countermeasures Program, Division of Allergy Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA

    Andrea L. DiCarlo & Bert W. Maidment

  2. Georgia Regents University Cancer Center, Augusta, GA, USA

    Joseph M. Kaminski

  3. Biomedical Advanced Research and Development Authority (BARDA), Department of Health and Human Services (HHS), Washington, DC, USA

    Richard J. Hatchett

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  1. Andrea L. DiCarlo
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  2. Joseph M. Kaminski
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  4. Bert W. Maidment
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Correspondence to Andrea L. DiCarlo.

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DiCarlo, A.L., Kaminski, J.M., Hatchett, R.J. et al. Role of thrombocytopenia in radiation-induced mortality and review of therapeutic approaches targeting platelet regeneration after radiation exposure. J Radiat Oncol 5, 19–32 (2016). https://doi.org/10.1007/s13566-015-0201-z

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  • DOI: https://doi.org/10.1007/s13566-015-0201-z

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