title: Differences in the mechanism of blood clot formation and nanostructure in infants and children compared with adults.
abstract: BACKGROUND
  Infants and children have a lower incidence of thrombosis compared with adults. Yet, the mechanism of blood clot formation and structure in infants and children, as the end product of coagulation, has not been studied. This study aimed to establish differences in the mechanism of thrombin generation, fibrin clot formation and response to thrombolysis in infants and children compared with adults.
  
  
  METHODS
  We studied thrombin generation, fibrin clot formation, structure and fibrinolysis in healthy infants, children and adults.
  
  
  RESULTS
  Younger populations had a decreased potential to generate thrombin, at a slower velocity compared with adults, correlating positively with age. Clot formation at venous shear rate was decreased in infants and children compared with adults, with increased time for fibrin formation, decreased fibrin formation velocity, resulting in decreased tendency for fibrin formation in younger populations. These differences were less pronounced at arterial shear rate. Studies of the fibrin clot structure in paediatric age groups showed a significantly larger pore size compared with adults, suggestive of a clot that is less resistant to fibrinolysis. The presence of tissue plasminogen activator (tPA) resulted in a significant decrease in the pore size of infants and children, but not in adults.
  
  
  CONCLUSIONS
  This is the first study to suggest that the mechanism of blood clot formation and nanostructure, as well as response to thrombolytic therapy is different in infants and children compared with adults.
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: vera.ignjatovic@mcri.edu.au.
authors.forename: Vera
authors.initials: V
authors.lastname: Ignjatovic
authors.affiliation: Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Pelkmans
authors.affiliation: Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Hilde
authors.initials: H
authors.lastname: Kelchtermans
authors.affiliation: Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Raed
authors.initials: R
authors.lastname: Al Dieri
authors.affiliation: Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Coen
authors.initials: C
authors.lastname: Hemker
authors.affiliation: Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Romy
authors.initials: R
authors.lastname: Kremers
authors.affiliation: Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Saartje
authors.initials: S
authors.lastname: Bloemen
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Karlaftis
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Chantal
authors.initials: C
authors.lastname: Attard
authors.affiliation: Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: de Laat
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Department of Clinical Hematology, Royal Children's Hospital, Parkville, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001777:Blood Coagulation / Q000276:immunology*; D001780:Blood Coagulation Tests / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D005337:Fibrin / Q000737:chemistry; D005342:Fibrinolysis; D064368:Healthy Volunteers; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D049329:Nanostructures / Q000737:chemistry; D013917:Thrombin / Q000737:chemistry*; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000737:chemistry; D055815:Young Adult
chemical_list: D005337:Fibrin; D013917:Thrombin; D010959:Tissue Plasminogen Activator
keywords: Child; Fibrin; Scanning electron microscopy; Thrombin; Tissue plasminogen activator