Evidence for radiation-induced disseminated intravascular coagulation as a major cause of radiation-induced death in ferrets.
OBJECTIVE
The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis.


METHODS
Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation.


RESULTS
The lethal dose of radiation to 50% of the population (LD50) of the ferrets was established at ∼ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days.


CONCLUSIONS
Data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Gabriel S
GS
Krigsfeld
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Alexandria R
AR
Savage
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Paul C
PC
Billings
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Liyong
L
Lin
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: akennedy@mail.med.upenn.edu.
Ann R
AR
Kennedy
D000818:Animals; D001772:Blood Cell Count; D001777:Blood Coagulation; D001792:Blood Platelets / Q000528:radiation effects; D002423:Cause of Death; D016923:Cell Death; D003359:Cosmic Radiation / Q000009:adverse effects*; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000401:mortality*; D005260:Female; D005289:Ferrets; D005720:Gamma Rays / Q000009:adverse effects; D006487:Hemostasis / Q000528:radiation effects; D007928:Lethal Dose 50; D011522:Protons / Q000009:adverse effects; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000150:complications / Q000401:mortality*; D019445:Solar Activity; D013026:Space Flight; D013916:Thrombelastography
D011522:Protons