Mechanism of hypocoagulability in proton-irradiated ferrets

Abstract

Purpose: To determine the mechanism of proton radiation- induced coagulopathy.

Material and 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.

Keywords::

• Radiation
• HZE particles
• low dose rate
• SPE radiation
• hemostasis

Acknowledgements

We would like to thank several LLUMC investigators for helping us with these studies; in particular, we thank Dr James M. Slater for allowing us to use the proton treatment and therapy center for our ferret proton exposures, as well as Drs Brian Bull and Karen Hay for training and use of the rapid soluble fibrin assay. We would also like to thank Drs Paul Billings, Salman Punekar, Tzvete Dentchev and Rodney Camire from the University of Pennsylvania for their assistance in radiation procedures and performance of these studies.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This research was supported by the NSBRI CARR grant. The NSBRI is funded through NASA NCC 9-58. This work was also funded by National Institutes of Health Training Grant 2T32CAO09677.