Abstract

Purpose

Total body irradiation of the Gottingen minipig results in a characteristic hematopoietic response, including anemia, neutropenia, lymphocytopenia, and thrombocytopenia. Currently, there are no well-characterized large or small animal models for radiation-induced thrombocytopenia. The study described here using the Gottingen minipig was focused on understanding which aspects of the coagulation cascade leads to radiation-induced coagulopathy. In this study, multiple clinical pathology parameters were determined prior to and for 45-days following total body irradiation using a 6 MV photon linear accelerator.

Materials and methods

Following irradiation, frequent analyses of conventional hematology and coagulation parameters provided time-course information on the onset and recovery of thrombocytopenia. In addition, thromboelastography (TEG) was utilized to monitor coagulation dysfunction, namely clotting time, clot formation time, clot strength, and fibrinolysis. Coagulation factor activity levels were measured for factors II, V, VII, VIII, IX, X, XI, XII, XIII, Protein C, fibrin monomers, antiplasmin and D-dimer using a Siemen’s coagulation analyzer to provide time course information of changes in activity post irradiation exposure.

Results

These analyses revealed that in total body irradiated minipigs, TEG tracings demonstrate long R (time to initial clot formation) and K (time to achieve a certain clot strength) times, and low alpha-angle (rate of clot formation) and MA (overall stability of the clot) during onset of thrombocytopenia (typically post irradiation day 10–15). Low alpha-angle and MA directly correlated with decreased platelet counts. A long R time is suggestive of a deficiency in clotting factors and was compared to measured activity levels of individual coagulation factors. The data indicates that coagulation factors are significantly changed early after irradiation exposure prior to thrombocytopenia and factors VIII, XI, XII and XIII are markedly altered during the critical point of thrombocytopenia.

Conclusion

These data support the continued use of multiple approaches to evaluate the coagulation cascade in order to provide the most meaningful interpretation of the hematopoietic changes that occur post irradiation.

中文翻译：

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辐射诱发凝血病的哥廷根小型猪模型

摘要

目的

对哥廷根小型猪进行全身照射会导致特征性造血反应，包括贫血、中性粒细胞减少、淋巴细胞减少和血小板减少。目前，对于辐射诱发的血小板减少症，没有充分表征的大型或小型动物模型。此处描述的使用哥廷根小型猪的研究的重点是了解凝血级联反应的哪些方面会导致辐射诱发的凝血病。在这项研究中，使用 6 MV 光子直线加速器在全身照射之前和之后的 45 天内确定了多个临床病理参数。

材料和方法

照射后，对常规血液学和凝血参数的频繁分析提供了有关血小板减少症发作和恢复的时间过程信息。此外，血栓弹力图 (TEG) 用于监测凝血功能障碍，即凝血时间、凝块形成时间、凝块强度和纤维蛋白溶解。使用西门子凝血分析仪测量凝血因子 II、V、VII、VIII、IX、X、XI、XII、XIII、蛋白 C、纤维蛋白单体、抗纤溶酶和 D-二聚体的凝血因子活性水平，以提供凝血因子变化的时间进程信息。辐照后的活动。

结果

这些分析表明，在全身辐照的小型猪中，TEG 描记显示 R（初始凝块形成的时间）和 K（达到一定凝块强度的时间）时间长，α 角（凝块形成率）和 MA（总体血小板减少症发作期间（通常在照射后第 10-15 天）。低α角和MA与血小板计数减少直接相关。较长的 R 时间表明凝血因子缺乏，并与测量的单个凝血因子的活性水平进行了比较。数据表明，在血小板减少症之前的辐射暴露后早期凝血因子发生显着变化，而凝血因子 VIII、XI、XII 和 XIII 在血小板减少症的临界点期间显着改变。

结论

这些数据支持继续使用多种方法来评估凝血级联，以便对照射后发生的造血变化提供最有意义的解释。