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
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
3936Références
Math Med Biol. 2009 Dec;26(4):323-36
pubmed: 19451209
Science. 1966 Apr 29;152(3722):651-3
pubmed: 17779507
J Thromb Haemost. 2013 Oct;11(10):1850-4
pubmed: 23927605
Blood. 1988 Nov;72(5):1651-7
pubmed: 3179444
Thromb Res. 2013 Feb;131(2):116-24
pubmed: 23260443
Br J Clin Pharmacol. 2015 Jun;79(6):959-66
pubmed: 25510952
Bull Math Biophys. 1948 Sep;10(3):175-86
pubmed: 18884378
Br J Anaesth. 2014 Feb;112(2):319-27
pubmed: 24193321
PLoS One. 2012;7(2):e30385
pubmed: 22319567
Thromb Haemost. 2016 Jun 2;115(6):1090-100
pubmed: 26819003
Am J Pediatr Hematol Oncol. 1990 Spring;12(1):95-104
pubmed: 2178462
Thromb Haemost. 2006 Feb;95(2):362-72
pubmed: 16493500
Clin Pharmacol Ther. 2009 Sep;86(3):290-8
pubmed: 19516255
Biochemistry. 1993 Jun 22;32(24):6266-74
pubmed: 8512937
Thromb Haemost. 2008 Apr;99(4):767-73
pubmed: 18392335
Blood. 1992 Oct 15;80(8):1998-2005
pubmed: 1391957
Front Physiol. 2014 Nov 07;5:417
pubmed: 25426077
Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8744-8
pubmed: 7568009
Haemostasis. 1991;21(4):197-207
pubmed: 1794746
J Biol Chem. 2002 May 24;277(21):18322-33
pubmed: 11893748
Anesth Analg. 2015 Aug;121(2):278-88
pubmed: 25839182