A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments.
A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments.
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DOI：
10.1667/rr14406.1
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发表时间：
2016-08
影响因子：
3.4
通讯作者：
Sanzari JK
中科院分区：
文献类型：
--
作者：
Kennedy AR;Maity A;Sanzari JK
从我们最近的研究结果导致了一个新的假设，即辐射诱导的凝血功能障碍（RIC）和相关的出血发生的急性辐射综合征（ARS）的一部分，是一个主要的死亡原因造成的辐射照射在大型哺乳动物，包括人类。本文包含与RIC相关的信息，以及预防和治疗RIC的潜在策略。此外，这里报告了关于暴露于辐射的人类中RIC生物标志物的发生的新发现。为了确定受照射的人是否具有RIC生物标志物，从接受不同类型恶性肿瘤治疗的放疗患者获得血液样品。在照射之前、期间和之后获得的来自异基因造血细胞移植（allo-HCT）患者的血液样本表明，暴露导致凝块形成时间延长、凝血酶-抗凝血酶III（达特）复合物水平升高和循环核小体/组蛋白（cNH）水平升高，这表明allo-HCT患者中存在潜在凝血病。由于这些allo-HCT患者在放疗前接受了化疗，因此化学药物可能会影响观察到的结果。还获得了来自患有前列腺癌、肺癌和乳腺癌的放射治疗患者的冷冻血浆样品用于分析cNH水平。结果表明，其中一些患者的cNH血液水平非常高。从辐照雪貂血浆样品中的cNH水平的分析也表明增加cNH水平相比，照射前的基线水平。来自辐照动物和一些放射治疗患者的结果表明，抗组蛋白抗体（其阻断血液中升高的cNH水平的毒性作用）可能用作不良生物辐射诱导效应的治疗剂。在一些放射治疗患者血液样本中检测到cNH水平升高，表明其作为诊断和/或预测发生凝血病/出血倾向的生物标志物的潜力，为癌症患者提供个性化药物治疗的可能治疗选择。
Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation. To determine whether irradiated humans have RIC biomarkers, blood samples were obtained from radiotherapy patients who received treatment for different types of malignancies. Blood samples from allogeneic hematopoietic cell transplantation (allo-HCT) patients obtained before, during and after irradiation indicated that exposure led to prolonged clot formation times, increased levels of thrombin-antithrombin III (TAT) complex and increased circulating nucleosome/ histone (cNH) levels, which suggest potential coagulopathies in the allo-HCT patients. Since these allo-HCT patients received chemotherapy prior to radiotherapy, it is possible that the chemical agents could have influenced the observed results. Frozen plasma samples from radiotherapy patients with prostate, lung and breast cancer were also obtained for analyses of cNH levels. The results indicated that some of these patients had very high cNH blood levels. Analysis of cNH levels in plasma samples from irradiated ferrets also indicated increased cNH levels compared to preirradiation baseline levels. The results from irradiated animals and some radiotherapy patients suggest the possibility that anti-histone antibodies, which block the toxic effects of elevated cNH levels in the blood, might be useful as therapeutic agents for adverse biological radiation-induced effects. The detection of increased levels of cNH in some radiotherapy patient blood samples demonstrates its potential as a biomarker for diagnosing and/or predicting the propensity for developing coagulopathies/hemorrhage, offering possible treatment options with personalized medicine therapies for cancer patients.
影响因子：
2.5
作者：
Sanzari, Jenine K;Billings, Paul C;Wilson, Jolaine M;Diffenderfer, Eric S;Arce-Esquivel, Arturo A;Thorne, Pamela K;Laughlin, Maurice H;Kennedy, Ann R
通讯作者：
Kennedy, Ann R