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Low paediatric thrombin generation is caused by an attenuation of prothrombin conversion.

Authors
  • Kremers, Romy M W1
  • Wagenvoord, Rob J
  • de Laat, H Bas
  • Monagle, Paul
  • Hemker, H Coenraad
  • Ignjatovic, Vera
  • 1 Romy Kremers, Oxfordlaan 70, 6229 EV, Maastricht, the Netherlands, Tel.: +31 43 388 5891, E-mail: [email protected] , (Netherlands)
Type
Published Article
Journal
Thrombosis and Haemostasis
Publisher
Georg Thieme Verlag KG
Publication Date
Jun 02, 2016
Volume
115
Issue
6
Pages
1090–1100
Identifiers
DOI: 10.1160/TH15-09-0716
PMID: 26819003
Source
Medline
Keywords
License
Unknown

Abstract

Thrombin generation (TG) is decreased in children. TG is determined by two underlying processes: the conversion of prothrombin to thrombin and the inactivation of thrombin. Therefore, lower TG capacity in children can either be caused by a reduction of prothrombin conversion, an increase of thrombin inactivation, or both. In 36 children and 8 adults, TG and the factors that determine thrombin inactivation (antithrombin, α2Macroglobulin (α2M) and fibrinogen) were measured. Prothrombin conversion, thrombin inhibitor complex formation, and the overall thrombin decay capacity were determined. In silico modelling was performed to determine the contribution prothrombin conversion and thrombin inactivation to deviant paediatric TG. Both the amount of prothrombin converted and the maximal prothrombin conversion rate are significantly reduced in children as compared to adults. This is partly due to the prothrombin levels being lower and partly to a lower prothrombin conversion rate. The overall thrombin decay capacity is not significantly different in children, but α2Macroglobulin plays a more important role than it does in adults. In silico experiments demonstrate that reduced prothrombin conversion and to a lesser extent elevated α2M levels provide an explanation for low TG in children. Young age has a dual effect on prothrombin conversion. Lower plasma prothrombin levels result in decreased prothrombin conversion but the rate of prothrombin conversion is also decreased, i. e. the development of prothrombinase is lower than in adults.

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