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

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. 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. 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. 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.