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

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.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events

“…346 Thrombocytopenia can result from cancer itself, chemotherapy, other medications, disseminated intravascular coagulation (DIC), radiation therapy, some infections, and pre-existing autoimmunity (particularly in patients with hematological cancers). [347][348][349][350][351][352][353][354][355][356] Because patients may already be experiencing thrombocytopenia as a result of cancer or due to a number of oncological treatment regimens, it may be prudent to establish a baseline platelet count and monitor for additional drops below this value when beginning ICI therapy. 357 The median time to onset for ITP is 41 days, and the median time for symptoms to resolve to below grade 2 is 4 weeks.…”

Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015

“…In turn, these molecules can modify the behavior of the cells. Radiation-induced platelet loss from the circulation leads to thrombocytopenia, and can play a major role in radiation-induced lethality (88). Fibrinogen-coated albumin nanospheres (FCN) have been shown to prevent bleeding from radiation-induced thrombocytopenia and vascular injury (A.…”

A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments

“…From the data on the casualties, it is estimated that 60–100% of the atomic bomb casualties receiving radiation doses near the LD 50 had evidence of hemorrhaging at death (6). There is now extensive evidence that bleeding/hemorrhage is a major problem in many different irradiated populations, as recently reviewed (85). …”