Vera Ignjatovic1, Leonie Pelkmans2, Hilde Kelchtermans2, Raed Al Dieri2, Coen Hemker2, Romy Kremers2, Saartje Bloemen2, Vasiliki Karlaftis3, Chantal Attard4, Bas de Laat2, Paul Monagle5. 1. Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: vera.ignjatovic@mcri.edu.au. 2. Synapse BV, CARIM, Maastricht University, Maastricht, Netherlands. 3. Murdoch Childrens Research Institute, Parkville, Victoria, Australia. 4. Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. 5. 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.
Abstract
INTRODUCTION: 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. MATERIALS AND 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.
INTRODUCTION: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. MATERIALS AND 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: Conor McCafferty; Leo Lee; Tengyi Cai; Slavica Praporski; Julian Stolper; Vasiliki Karlaftis; Chantal Attard; David Myint; Leeanne M Carey; David W Howells; Geoffrey A Donnan; Stephen Davis; Henry Ma; Sheila Crewther; Vinh A Nguyen; Suelyn Van Den Helm; Natasha Letunica; Ella Swaney; David Elliott; Kanta Subbarao; Vera Ignjatovic; Paul Monagle Journal: EJHaem Date: 2022-03-22