title: Mechanism of hypocoagulability in proton-irradiated ferrets.
abstract: OBJECTIVE
  To determine the mechanism of proton radiation- induced coagulopathy.
  
  
  METHODS
  Ferrets were exposed to either solar particle event (SPE)-like proton radiation at a predetermined dose rate of 0.5 Gray (Gy) per hour (h) for a total dose of 0 or 1 Gy. Blood was collected pre- and post-irradiation for a complete blood cell count or a soluble fibrin concentration analysis, to determine whether coagulation activation had occurred. Tissue was stained with an anti-fibrinogen antibody to confirm the presence of fibrin in blood vessels.
  
  
  RESULTS
  SPE-like proton radiation exposure resulted in coagulation cascade activation, as determined by increased soluble fibrin concentration in blood from 0.7-2.4 at 3 h, and 9.9 soluble fibrin units (p < 0.05) at 24 h post-irradiation and fibrin clots in blood vessels of livers, lungs and kidneys from irradiated ferrets. In combination with this increase in fibrin clots, ferrets had increased prothrombin time and partial thromboplastin time values post-irradiation, which are representative of the extrinsic/intrinsic coagulation pathways. Platelet counts remained at pre-irradiation values over the course of 7 days, indicating that the observed effects were not platelet-related, but instead likely to be due to radiation-induced effects on secondary hemostasis. White blood cell (WBC) counts were reduced in a statistically significant manner from 24 h through the course of the seven-day experiment.
  
  
  CONCLUSIONS
  SPE-like proton radiation results in significant decreases in all WBC counts as well as activates secondary hemostasis; together, these data suggest severe risks to astronaut health from exposure to SPE radiation.
authors: Department of Radiation Oncology, University of Pennsylvania , Philadelphia, PA.
authors: Gabriel S
authors: GS
authors: Krigsfeld
authors: Alexandria R
authors: AR
authors: Savage
authors: Jenine K
authors: JK
authors: Sanzari
authors: Andrew J
authors: AJ
authors: Wroe
authors: Daila S
authors: DS
authors: Gridley
authors: Ann R
authors: AR
authors: Kennedy
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects / Q000528:radiation effects*; D005164:Factor IX / Q000494:pharmacology; D005289:Ferrets; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism; D011522:Protons / Q000009:adverse effects*; D019445:Solar Activity; D012995:Solubility; D010837:Vitamin K 1 / Q000494:pharmacology
chemical_list: D011522:Protons; D010837:Vitamin K 1; D005164:Factor IX; D005337:Fibrin
references: Blood. 1964 Feb;23:186-92
references: 14122243
references: Haemophilia. 2010 Jan;16(1):e216-22
references: 19878330
references: J Bacteriol. 1956 Feb;71(2):188-95
references: 13295192
references: Radiat Res Suppl. 1967;7:336-59
references: 4964579
references: Vet Clin Pathol. 2008 Sep;37(3):286-8
references: 18761520
references: Med Phys. 1991 Nov-Dec;18(6):1093-9
references: 1661367
references: Cell. 1988 May 20;53(4):505-18
references: 3286010
references: Int J Radiat Biol Relat Stud Phys Chem Med. 1988 Mar;53(3):439-56
references: 3257956
references: Med Phys. 2013 Apr;40(4):041702
references: 23556872
references: Cell Transplant. 2012;21(2-3):437-45
references: 22793051
references: Adv Space Res. 1992;12(2-3):195-200
references: 11537008
references: Circulation. 1999 Jan 19;99(2):299-304
references: 9892598
references: Health Phys. 2009 Jul;97(1):68-81
references: 19509510
references: J Lab Clin Med. 1951 Sep;38(3):331-43
references: 14880746
references: Health Phys. 2009 Apr;96(4):465-76
references: 19276707
references: Acta Astronaut. 2005 May-Jun;56(9-12):969-74
references: 15835055
references: Technol Cancer Res Treat. 2007 Aug;6(4 Suppl):41-8
references: 17668951
references: Int J Radiat Biol. 2012 Apr;88(4):327-34
references: 22221163
references: Naturwissenschaften. 2007 Jul;94(7):517-26
references: 17235598
references: PLoS One. 2011;6(9):e25210
references: 21969873
references: Thromb Haemost. 2002 Nov;88(5):773-80
references: 12428093
references: Radiat Prot Dosimetry. 2005;115(1-4):44-50
references: 16381680
references: J Vet Emerg Crit Care (San Antonio). 2009 Feb;19(1):3-10
references: 19691581
references: Br J Haematol. 2009 Apr;145(1):24-33
references: 19222477
references: Adv Space Res. 2012 Jan 1;49(2):237-248
references: 23766550
references: Annu Rev Med. 1954;5:323-38
references: 13181380
references: Mutat Res. 2009 Apr 26;663(1-2):32-9
references: 19428367
references: Lab Anim Sci. 1995 Apr;45(2):151-9
references: 7603015
references: Radiat Res. 2001 Nov;156(5 Pt 2):682-8
references: 11604093
references: Acta Astronaut. 1998 Jan-Apr;42(1-8):107-14
references: 11541595
references: Radiat Res. 1988 Jun;114(3):599-612
references: 3375446