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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
08 03 2019
Historique:
received: 17 07 2018
accepted: 13 02 2019
entrez: 10 3 2019
pubmed: 10 3 2019
medline: 30 9 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 30850652
doi: 10.1038/s41598-019-40435-7
pii: 10.1038/s41598-019-40435-7
pmc: PMC6408458
doi:

Substances chimiques

Prothrombin 9001-26-7
Thrombin EC 3.4.21.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3936

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Auteurs

Ivo Siekmann (I)

Liverpool John Moores University, Department of Applied Mathematics, Liverpool, L3 3AF, England. i.siekmann@ljmu.ac.uk.
The University of Melbourne, Systems Biology Laboratory, 813 Swanston Street, Parkville, Victoria, 3010, Australia. i.siekmann@ljmu.ac.uk.

Stefan Bjelosevic (S)

Murdoch Children's Research Institute, Haematology Research, 50 Flemington Road, Parkville, Victoria, 3052, Australia.
The University of Melbourne, The Sir Peter MacCallum Department of Oncology, 305 Grattan Street, Melbourne, Victoria, 3000, Australia.

Kerry Landman (K)

The University of Melbourne, School of Mathematics and Statistics, 813 Swanston Street, Parkville, Victoria, 3010, Australia.

Paul Monagle (P)

Murdoch Children's Research Institute, Haematology Research, 50 Flemington Road, Parkville, Victoria, 3052, Australia.
Royal Children's Hospital, Department of Clinical Haematology, 50 Flemington Road, Parkville, Victoria, 3052, Australia.
The University of Melbourne, Department of Paediatrics, 50 Flemington Road, Parkville, Victoria, 3052, Australia.

Vera Ignjatovic (V)

Murdoch Children's Research Institute, Haematology Research, 50 Flemington Road, Parkville, Victoria, 3052, Australia.
The University of Melbourne, Department of Paediatrics, 50 Flemington Road, Parkville, Victoria, 3052, Australia.

Edmund J Crampin (EJ)

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.
The University of Melbourne, School of Mathematics and Statistics, 813 Swanston Street, Parkville, Victoria, 3010, Australia.
The University of Melbourne, School of Medicine, Grattan Street, Parkville, Victoria, 3010, Australia.

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Classifications MeSH