Thromb Haemost 2016; 115(06): 1090-1100
DOI: 10.1160/TH15-09-0716
Coagulation and Fibrinolysis
Schattauer GmbH

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

Romy M. W. Kremers
1   Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
2   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
,
Rob J. Wagenvoord
1   Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
,
H. Bas de Laat
1   Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
2   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
,
Paul Monagle
3   Murdoch Childrens Research Institute, Parkville, Victoria, Australia
4   Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
5   Department of Clinical Hematology, Royal Children’s Hospital, Parkville, Victoria, Australia
,
H. Coenraad Hemker
1   Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
2   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
,
Vera Ignjatovic
3   Murdoch Childrens Research Institute, Parkville, Victoria, Australia
4   Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
› Author Affiliations
Further Information

Publication History

Received: 09 September 2015

Accepted after major revision: 13 January 2016

Publication Date:
27 November 2017 (online)

Preview

Summary

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, α2 Macroglobulin (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.