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Thromb Haemost 2010; 103(06): 1181-1187
DOI: 10.1160/TH09-06-0376
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Reduced ADAMTS13 in children with severe meningococcal sepsis is associated with severity and outcome

Tamara N. Bongers
1   Department of Hematology, Erasmus MC, Rotterdam, the Netherlands
,
Marieke Emonts
2   Department of Pediatrics, Erasmus MC-Sophia Childrens’s Hospital, University Medical Center Rotterdam, the Netherlands
5   Department of Immunology, Erasmus MC-Sophia Childrens’s Hospital, University Medical Center Rotterdam, the Netherlands
,
Moniek P. M. de Maat
1   Department of Hematology, Erasmus MC, Rotterdam, the Netherlands
,
Ronald de Groot
3   Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
,
Ton Lisman
4   Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, The Netherlands
,
Jan A. Hazelzet
2   Department of Pediatrics, Erasmus MC-Sophia Childrens’s Hospital, University Medical Center Rotterdam, the Netherlands
,
Frank W. G. Leebeek
1   Department of Hematology, Erasmus MC, Rotterdam, the Netherlands
› Author Affiliations
Further Information

Publication History

Received: 17 June 2009

Accepted after major revision: 19 February 2010

Publication Date:
22 November 2017 (online)

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Summary

Multiple organ failure is a common feature of pediatric meningococcal sepsis and is associated with an imbalance of coagulation and fibrinolysis. This is partly due to an increased secretion of prothrombotic ultra-large von Willebrand factor (VWF) as the result of vascular endothelial damage. Another factor that may contribute is ADAMTS13, which converts VWF into smaller, less active, VWF multimers and thus influences VWF activity in plasma. We investigated the role of ADAMTS13 and VWF in the severity and outcome of sepsis. In 58 children with severe meningococcal sepsis we measured ADAMTS13 activity and antigen, VWF collagen binding activity (VWF:CB) and antigen levels (VWF:Ag), VWF propeptide and factor VIII at different time points during their stay in the paediatric intensive care unit. In the acute phase, both ADAMTS13 activity and antigen were decreased (median 23.4% and 33.7% of normal, respectively) and VWF:CB and VWF:Ag levels were strongly increased (325% and 348%, respectively.) ADAMTS13 antigen (23.9% vs. 34.6%; p=0.06) and VWF:CB (240% and 340% p<0.001) were lower in non-survivors than in survivors. ADAMTS13 activity and VWF:CB were both correlated with the severity of the disease, as indicated by the Pediatric Risk of Mortality score (Rs= –0.38 and Rs= –0.50, p=0.01, respectively, p<0.001). In the acute phase of severe sepsis decreased levels of ADAMTS13 and increased levels of VWF are observed, and the changes are related to severity of disease and outcome. This may contribute to the formation of microthrombi and the severity of thrombotic sequelae of sepsis.

Keywords

ADAMS/ADAMTS 13 - disseminated intravascular coagulation (DIC) - fibrinolytic disorders - paediatric haemostasis - sepsis
 

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