Gabriel S Krigsfeld1, Alexandria R Savage1, Paul C Billings1, Liyong Lin1, Ann R Kennedy2. 1. Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 2. Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: akennedy@mail.med.upenn.edu.
Abstract
PURPOSE: 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 AND MATERIALS: 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.
PURPOSE: 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 AND MATERIALS: 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.
Authors: Chris O Wambi; Jenine K Sanzari; Carly M Sayers; Manunya Nuth; Zhaozong Zhou; James Davis; Niklas Finnberg; Joan S Lewis-Wambi; Jeffrey H Ware; Wafik S El-Deiry; Ann R Kennedy Journal: Radiat Res Date: 2009-08 Impact factor: 2.841
Authors: Maria Moroni; Eric Lombardini; Rudolph Salber; Mehdi Kazemzedeh; Vitaly Nagy; Cara Olsen; Mark H Whitnall Journal: PLoS One Date: 2011-09-28 Impact factor: 3.240
Authors: Jenine K Sanzari; Gabriel S Krigsfeld; Anne L Shuman; Antonia K Diener; Liyong Lin; Wilfried Mai; Ann R Kennedy Journal: Life Sci Space Res (Amst) Date: 2015-04
Authors: Carmen I Rios; David R Cassatt; Brynn A Hollingsworth; Merriline M Satyamitra; Yeabsera S Tadesse; Lanyn P Taliaferro; Thomas A Winters; Andrea L DiCarlo Journal: Radiat Res Date: 2021-01-01 Impact factor: 2.841
Authors: Eric P Cohen; Kim G Hankey; Alexander W Bennett; Ann M Farese; George A Parker; Thomas J MacVittie Journal: Radiat Res Date: 2017-10-16 Impact factor: 2.841
Authors: Barbara Olszewska-Pazdrak; Scott D McVicar; Kempaiah Rayavara; Stephanie M Moya; Carla Kantara; Chris Gammarano; Paulina Olszewska; Gerald M Fuller; Laurie E Sower; Darrell H Carney Journal: Radiat Res Date: 2016-07-07 Impact factor: 2.841