Pathophysiological principles underlying the blood cell concentration responses used to assess the severity of effect after accidental whole-body radiation exposure: An essential basis for an evidence-based clinical triage

Objective The objective of this review is to provide a scientific justification for using the pattern of changes of granulocytes, platelets, and lymphocytes within the first few days after an accidental whole-body exposure to ionizing radiation as a convincing indicator of the severity of its effect on the hematopoietic stem cell pool. Method The availability of the SEARCH database system (System for Evaluation and Archiving of Radiation Accidents based on Case Histories) allowed us to analyze the “early” blood cell changes after accidental whole-body radiation exposure in more than 100 patients and to assign them to severity of effect code H4 and H3, described in the METREPOL approach. Results A specific pattern of blood cell changes (granulocytes, platelets, lymphocytes) within the first 5 to 8 days after exposure is compatible with the assumption of an irreversible damage of the stem cell pool distributed throughout the skeletal bone marrow designated as H4. Distinguishable from this pattern is a blood cell response pattern characterized by an “abortive recovery,” which can be explained by the “injured cell hypothesis,” allowing to assign these patients to a severity-of-effect-code H3, H2, or H1 compatible with the assumption of a “reversible” damage to the stem cell pool. Biomathematical models allow one to correlate the blood cell change patterns with the extent of damage to the stem cell pool. Conclusion Patterns of change in peripheral blood cell counts indicate the effect of radiation on the hematopoietic stem cell pool, and have the potential to predict autochthonous regeneration.