Liverpool John Moores University, Department of Applied Mathematics, Liverpool, L3 3AF, England.
The University of Melbourne, Systems Biology Laboratory, 813 Swanston Street, Parkville, Victoria, 3010, Australia.
Sci Rep. 2019 Mar 8;9(1):3936. doi: 10.1038/s41598-019-40435-7.
Haemostasis is governed by a highly complex system of interacting proteins. Due to the central role of thrombin, thrombin generation and specifically the thrombin generation curve (TGC) is commonly used as an indicator of haemostatic activity. Functional characteristics of the haemostatic system in neonates and children are significantly different compared with adults; at the same time plasma levels of haemostatic proteins vary considerably with age. However, relating one to the other has been difficult, both due to significant inter-individual differences for individuals of similar age and the complexity of the biochemical reactions underlying haemostasis. Mathematical modelling has been very successful at representing the biochemistry of blood clotting. In this study we address the challenge of large inter-individual variability by parameterising the Hockin-Mann model with data from individual patients, across different age groups from neonates to adults. Calculating TGCs for each patient of a specific age group provides us with insight into the variability of haemostatic activity across that age group. From our model we observe that two commonly used metrics for haemostatic activity are significantly lower in neonates than in older patients. Because both metrics are strongly determined by prothrombin and prothrombin levels are considerably lower in neonates we conclude that decreased haemostatic activity in neonates is due to lower prothrombin availability.
止血是由一个高度复杂的相互作用的蛋白质系统控制的。由于凝血酶的核心作用，凝血酶生成和特别是凝血酶生成曲线（TGC）通常被用作止血活性的指标。与成年人相比，新生儿和儿童的止血系统的功能特征有很大的不同；同时，止血蛋白的血浆水平随年龄有很大的差异。然而，将两者联系起来一直很困难，这既是由于相似年龄的个体之间存在显著的个体差异，也是由于止血的生化反应的复杂性。数学模型在表示血液凝固的生物化学方面非常成功。在这项研究中，我们通过使用来自个体患者的数据对 Hockin-Mann 模型进行参数化，解决了个体间差异大的挑战，涵盖了从新生儿到成年人的不同年龄组。为特定年龄组的每个患者计算 TGC，使我们能够深入了解该年龄组内止血活性的可变性。从我们的模型中，我们观察到，两种常用的止血活性度量在新生儿中明显低于年龄较大的患者。由于这两个度量都强烈取决于凝血酶原，而凝血酶原在新生儿中明显较低，我们得出结论，新生儿的止血活性降低是由于凝血酶原的可用性降低所致。
