比较猪血浆和人血浆中新生儿和成人纤维蛋白凝块特性。
Comparison of Neonatal and Adult Fibrin Clot Properties between Porcine and Human Plasma.
机构信息
From the Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, North Carolina (K.A.N., S.N., A.K., S.S., A.C.B.) the Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina (K.A.N., A.C.B.) the Department of Anesthesiology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia (N.A.G.).
出版信息
Anesthesiology. 2020 May;132(5):1091-1101. doi: 10.1097/ALN.0000000000003165.
BACKGROUND
Recent studies suggest that adult-specific treatment options for fibrinogen replacement during bleeding may be less effective in neonates. This is likely due to structural and functional differences found in the fibrin network between adults and neonates. In this investigation, the authors performed a comparative laboratory-based study between immature and adult human and porcine plasma samples in order to determine if piglets are an appropriate animal model of neonatal coagulopathy.
METHODS
Adult and neonatal human and porcine plasma samples were collected from the Children's Hospital of Atlanta and North Carolina State University College of Veterinary Medicine, respectively. Clots were formed for analysis and fibrinogen concentration was quantified. Structure was examined through confocal microscopy and cryogenic scanning electron microscopy. Function was assessed through atomic force microscopy nanoindentation and clotting and fibrinolysis assays. Lastly, novel hemostatic therapies were applied to neonatal porcine samples to simulate treatment.
RESULTS
All sample groups had similar plasma fibrinogen concentrations. Neonatal porcine and human plasma clots were less branched with lower fiber densities than the dense and highly branched networks seen in adult human and porcine clots. Neonatal porcine and human clots had faster degradation rates and lower clot stiffness values than adult clots (stiffness [mmHg] mean ± SD: neonatal human, 12.15 ± 1.35 mmHg vs. adult human, 32.25 ± 7.13 mmHg; P = 0.016; neonatal pig, 10.5 ± 8.25 mmHg vs. adult pigs, 32.55 ± 7.20 mmHg; P = 0.015). The addition of hemostatic therapies to neonatal porcine samples enhanced clot formation.
CONCLUSIONS
The authors identified similar age-related patterns in structure, mechanical, and degradation properties between adults and neonates in porcine and human samples. These findings suggest that piglets are an appropriate preclinical model of neonatal coagulopathy. The authors also show the feasibility of in vitro model application through analysis of novel hemostatic therapies as applied to dilute neonatal porcine plasma.
背景
最近的研究表明，在出血时，针对纤维蛋白原替代的成人特异性治疗选择在新生儿中可能效果较差。这很可能是由于成人和新生儿纤维蛋白网络中的结构和功能差异所致。在这项研究中，作者对不成熟和成人人类及猪血浆样本进行了对比实验室研究，以确定小猪是否是新生儿凝血障碍的合适动物模型。
方法
从亚特兰大儿童医院和北卡罗来纳州立大学兽医学院分别收集成人和新生儿的人类和猪血浆样本。分析形成的凝块并定量纤维蛋白原浓度。通过共聚焦显微镜和冷冻扫描电子显微镜检查结构。通过原子力显微镜纳米压痕和凝血及纤维蛋白溶解测定评估功能。最后，应用新型止血疗法模拟治疗对新生猪样本进行处理。
结果
所有样本组的血浆纤维蛋白原浓度均相似。与成人人类和猪凝块中所见的密集且高度分支的网络相比，新生猪和人类血浆凝块分支较少，纤维密度较低。新生猪和人类凝块的降解速度较快，且凝块硬度值较低（硬度[mmHg]均值±SD：新生人类，12.15±1.35mmHg 比成人人类，32.25±7.13mmHg；P=0.016；新生猪，10.5±8.25mmHg 比成年猪，32.55±7.20mmHg；P=0.015）。将止血疗法添加到新生猪样本中可增强凝块形成。
结论
作者在猪和人类样本中发现了成人和新生儿之间在结构、力学和降解特性方面相似的年龄相关模式。这些发现表明小猪是新生儿凝血障碍的合适临床前模型。作者还通过分析应用于稀释的新生猪血浆的新型止血疗法，展示了体外模型应用的可行性。
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