Mechanism of hypocoagulability in proton-irradiated ferrets

Krigsfeld, Gabriel; Savage, Alexandria R.; Sanzari, Jenine K.; Wroe, Andrew; Gridley, Daila S.; Kennedy, Ann R.

doi:10.3109/09553002.2013.802394

Cited by 16 publications

(20 citation statements)

References 31 publications

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“…A reduction in the number of platelets can result in hemorrhaging and death; however, our results in irradiated ferrets suggest that a reduction in the number of platelets does not cause the blood clotting abnormalities leading to DIC after radiation exposure (3, 4). We have reported that platelet cell counts in ferrets exposed to a 1 Gy dose of SPE proton radiation are not significantly different from control levels over 7 days postirradiation.…”

mentioning

confidence: 53%

“…Ferrets exposed to SPE radiation have increased clotting times and factor deficiencies, indicating hypocoagulability (3). Our current studies in ferrets have shown that SPE proton radiation exposure at 1 Gy leads to increased bleeding times, concentrations of soluble fibrin in blood, and fibrin clotting in the livers, lungs and kidneys of irradiated ferrets within 24 h postirradiation (3, 4). The measurement of soluble fibrin in the blood is a marker for DIC in the clinic (5).…”

mentioning

confidence: 85%

“…We have reported that platelet cell counts in ferrets exposed to a 1 Gy dose of SPE proton radiation are not significantly different from control levels over 7 days postirradiation. During this time period, the irradiated ferrets exhibit serious blood clotting abnormalities while the platelet counts are well within the normal range (4). The platelet counts are significantly reduced at times of overt or “terminal” DIC in ferrets, but they do not appear to play an important role in the early changes leading to full-blown DIC.…”

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confidence: 99%

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Is Disseminated Intravascular Coagulation the Major Cause of Mortality from Radiation at Relatively Low Whole Body Doses?

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confidence: 53%

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confidence: 85%

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confidence: 99%

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Is Disseminated Intravascular Coagulation the Major Cause of Mortality from Radiation at Relatively Low Whole Body Doses?

Krigsfeld

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2013

Radiation Research

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“…We have hypothesized that the SPE-like proton irradiation activates the coagulation cascade, which would put irradiated subjects in a hypocoagulable state. To test this hypothesis, a separate experiment was performed with 12 to 15 week old de-scented female ferrets irradiated with 1 Gy of 110-MeV protons at a dose rate of 0.5 Gy/hour, and the results indicate that the radiation exposure resulted in coagulation cascade activation, which was indicated by increases in soluble fibrin concentration in the blood and fibrin clots in blood vessels of livers, lungs and kidneys from irradiated ferrets (208). The soluble fibrin concentration was determined using a rapid soluble fibrin assay that was previously developed and implemented at the Loma Linda University Medical Center to aid in early detection of DIC in emergency room, operating room, or transplant patients (209).…”

Section: Acute Radiation Effectsmentioning

confidence: 99%

Biological effects of space radiation and development of effective countermeasures

Kennedy

2014

Life Sciences in Space Research

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150

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As part of a program to assess the adverse biological effects expected from astronaut exposure to space radiation, numerous different biological effects relating to astronaut health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronaut vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

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“…6 Animal experiments in minipigs 60 suggest that the RBE for acute radiation syndrome of protons in simulated SPE is .1. Ferrets exposed to SPE-like protons had increase in fibrin clots, prothrombin time and partial thromboplastin time values post-irradiation, 61 suggesting a proton radiation-induced coagulopathy, which represents a risk for SPE in space but may find important applications in CPT.…”

Section: Hypofractionationmentioning

confidence: 99%

New challenges in high-energy particle radiobiology

Durante

2014

BJR

123

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Densely ionizing radiation has always been a main topic in radiobiology. In fact, a-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space.Biological effects of densely ionizing radiation have been studied since the beginning of radiobiology. As a matter of fact, a-particles deliver the main contribution to the background radiation dose on Earth, owing to inhalation of the indoor radon.1 Neutrons have also been extensively studied because of protection of workers in nuclear power plants; use of fast neutrons in radiotherapy; and of the exposure of the survivors of the atomic bomb in Hiroshima and Nagasaki, where a neutron component was added to g-rays. Bacq and Alexander 2 already elegantly described the radiobiology of a-particles and neutrons in their 1955 seminal book.More recently, radiobiology research has focused on highenergy protons and heavy ions, mostly for two reasons: charged particle therapy (CPT) in oncology and radiation protection in manned space missions. In both cases, charged particles at energies .100 MeV n 21 are involved. The characteristic depth-dose distribution with the sharp Bragg peak at the end of the range can be exploited for killing tumours; on the other hand, densely ionizing radiation can effectively delay tissue morbidity. Notwithstanding the many differences in exposure conditions, CPT and space radiation protection share several research topics, including individual sensitivity, non-targeted effects, late stochastic effects and so forth.3 Research in these fields requires large high-energy accelerators and is often performed by the same research groups with a common interest in particle radiobiology. Research is rapidly moving forward owing to the diffusion of CPT centres in the USA, Europe, and Asia 4 and to the growing interest in manned space exploration, now a priority for all space agencies, 5 but wi...

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Mechanism of hypocoagulability in proton-irradiated ferrets

Cited by 16 publications

References 31 publications

Is Disseminated Intravascular Coagulation the Major Cause of Mortality from Radiation at Relatively Low Whole Body Doses?

Is Disseminated Intravascular Coagulation the Major Cause of Mortality from Radiation at Relatively Low Whole Body Doses?

Biological effects of space radiation and development of effective countermeasures

New challenges in high-energy particle radiobiology

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