Mathematical modelling indicates that lower activity of the haemostatic system in neonates is primarily due to lower prothrombin concentration

TL;DR

This study uses mathematical modelling to show that lower haemostatic activity in neonates is mainly caused by reduced prothrombin levels, highlighting age-related biochemical differences.

Contribution

The paper introduces a patient-specific parameterisation of the Hockin-Mann model across age groups, linking lower neonatal haemostatic activity to prothrombin deficiency.

Findings

Neonates have significantly lower haemostatic metrics than older individuals.

Prothrombin levels are considerably lower in neonates.

Lower prothrombin availability explains decreased haemostatic activity in neonates.

Abstract

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.