A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments

Kennedy, Ann R.; Maity, Amit; Sanzari, Jenine K.

doi:10.1667/rr14406.1

Cited by 43 publications

(30 citation statements)

References 117 publications

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“…Previous studies investigating conventional RT and IMRT techniques have reported a decrease in platelet count following treatment, thus corroborating the results of the present study (7,15,38,39). Furthermore, it has been demonstrated that sub-lethal radiation doses may result in abnormal hemostasis characteristics and coagulation biomarker values observed up to 21 days post-irradiation (40). Therefore, the post-RT decrease in platelet counts observed in the present study may be due to the suppressive effect of radiation on the hematopoietic system in the acute phase.…”

Section: Discussionsupporting

confidence: 92%

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy

et al. 2018

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Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation.

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Section: Discussionsupporting

confidence: 92%

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy

et al. 2018

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“…162 The use of anticoagulants such as heparin has been investigated, but the results to date have been mostly insignificant and generally inconsistent. 163 In contrast, the TM-APC pathway is a hopeful target for preventing or treating radiation toxicity in normal tissues using strategies aimed at restoring or preserving endothelial TM or replacing protein C. 156,164,165 Also, thrombin inhibition has been investigated as a strategy to minimise the side-effects of RT. The recombinant thrombin inhibitor hirudin has shown a protective effect against small bowel radiation toxicity in a model of localised small bowel radiation in rats.…”

Section: Decreasing Coagulopathymentioning

confidence: 99%

The importance of the vascular endothelial barrier in the immune-inflammatory response induced by radiotherapy

Guipaud

Jaillet

Clément-Colmou

et al. 2018

BJR

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Altered by ionising radiation, the vascular network is considered as a prime target to limit normal tissue damage and improve tumour control in radiotherapy (RT). Irradiation damages and/or activates endothelial cells, which then participate in the recruitment of circulating cells, especially by overexpressing cell adhesion molecules, but also by other as yet unknown mechanisms. Radiation-induced lesions are associated with infiltration of immune-inflammatory cells from the blood and/or the lymph circulation. Damaged cells from the tissues and immune-inflammatory resident cells release factors that attract cells from the circulation, leading to the restoration of tissue balance by fighting against infection, elimination of damaged cells and healing of the injured area. In normal tissues that surround the tumours, the development of an immune-inflammatory reaction in response to radiation-induced tissue injury can turn out to be chronic and deleterious for the organ concerned, potentially leading to fibrosis and/or necrosis of the irradiated area. Similarly, tumours can elicit an immune-inflammation reaction, which can be initialised and amplified by cancer therapy such as radiotherapy, although immune checkpoints often allow many cancers to be protected by inhibiting the T-cell signal. Herein, we have explored the involvement of vascular endothelium in the fate of healthy tissues and tumours undergoing radiotherapy. This review also covers current investigations that take advantage of the radiation-induced response of the vasculature to spare healthy tissue and/or target tumours better.

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“…Fibrinogen deficiency suppresses the development of early and delayed radiation-induced enteropathy, characteristically mediated by endothelial injury, suggesting a role for fibrinogen in mediation of endothelial injury. 35,36 Oxidized low-density lipoprotein (ox-LDL) augments radiation-induced phenotypic changes like upregulation of alpha-smooth muscle actin (α-SMA), fibroblast-specific protein-1 (FSP-1), and vimentin. This transition to mesenchymal phenotype favors acceleration of atherosclerosis.…”

Section: Blood-based Biomarkersmentioning

confidence: 99%

“…Fibrinogen acts as an acute indicator of radiation‐induced activation of the coagulation cascade. Fibrinogen deficiency suppresses the development of early and delayed radiation‐induced enteropathy, characteristically mediated by endothelial injury, suggesting a role for fibrinogen in mediation of endothelial injury . Oxidized low‐density lipoprotein (ox‐LDL) augments radiation‐induced phenotypic changes like upregulation of alpha‐smooth muscle actin (α‐SMA), fibroblast‐specific protein‐1 (FSP‐1), and vimentin.…”

Section: Blood‐based Biomarkersmentioning

confidence: 99%

Biomarkers of radiation‐induced vascular injury

et al. 2018

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Objective Cancer survivorship has thrown the spotlight on the incidence of nonmalignant chronic diseases in cancer patients. Endothelial injury is increasingly recognized as a consequence of cancer treatment, particularly after radiation therapy (RT). This review is to provide a current understanding on the pathophysiological mechanisms and predictive biomarkers of radiation‐induced vascular injury. Recent findings Radiation directly impacts vasculature by causing endothelial apoptosis and senescence, and alterations in normal homeostasis. This altered milieu at the endothelial surface may contribute to a systemic chronic inflammatory state that is superimposed upon the cascade of normal senescence processes leading to acceleration of age‐related disorders, atherosclerosis, and chronic fibrosis. Vasculature imaging, blood‐based or cell‐component biomarkers, and signatures of genomics, proteomics, metabolomics, and radiomics are potential tools for detection of vascular damage after irradiation. Conclusions Development of a valid prediction model by combining an array of imaging tools, blood‐based biomarkers, coupled with novel predictors like exosomes and metabolic degradation products can serve to identify RT‐induced vascular injury early for subsequent introduction of newer therapeutic approaches to counter radiation morbidity.

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A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments

Cited by 43 publications

References 117 publications

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy

The importance of the vascular endothelial barrier in the immune-inflammatory response induced by radiotherapy

Biomarkers of radiation‐induced vascular injury

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