The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets.
OBJECTIVE
To determine whether proton radiation affects coagulation.


METHODS
Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3-7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved.


RESULTS
HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0.


CONCLUSIONS
PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy.
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Gabriel S
GS
Krigsfeld
Jenine K
JK
Sanzari
Ann R
AR
Kennedy
D000818:Animals; D001777:Blood Coagulation / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005289:Ferrets; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000378:metabolism*; D011517:Prothrombin Time; D011522:Protons / Q000009:adverse effects*; D012149:Restraint, Physical; D019445:Solar Activity; D013925:Thromboplastin / Q000378:metabolism*; D013997:Time Factors
D011522:Protons; D011516:Prothrombin; D013925:Thromboplastin