title: Whole blood coagulation in children with thrombocytopenia and the response to platelet replacement, recombinant factor VIIa, and a potent factor VIIa analogue.
abstract: The present study evaluated dynamic coagulation profiles, platelet aggregation, and thrombin generation in whole blood (WB) from eight children with thrombocytopenia during chemotherapy, and the haemostatic potential of platelets (+60 x 10(9)/l), recombinant factor VIIa (rFVIIa - NovoSeven), and a potent rFVIIa analogue (NN1731) both at 1 and 4 microg/ml. Dynamic WB coagulation profiles were recorded by thrombelastometry employing activation with tissue factor (TF - Innovin) at low concentrations. The baseline WB coagulation patterns were characterised by a prolonged clotting time (CT) and a pronounced reduction in clot propagation (MaxVel). WB platelet aggregation signal was five times lower in the study group compared with measurements in modelled thrombocytopenic WB from healthy volunteers. In vitro addition of fresh platelets reversed the coagulopathy. Addition of rFVIIa induced no significant changes in the thrombelastographic profile, whereas spiking with NN1731 shortened the CT significantly. The changes in WB thrombin generation reflected the changes in the MaxVel. In modeled thrombocytopenic WB from healthy individuals, both rFVIIa and NN1731 exhibited a pronounced haemostatic effect with NN1731 showing greater potency than rFVIIa. Compromised platelet function in the study group was assumingly responsible for the weakened haemostatic potential of rFVIIa as well as that of NN1731.
authors.affiliation: Centre for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark.
authors.forename: Ole H
authors.initials: OH
authors.lastname: Larsen
authors.forename: Niels
authors.initials: N
authors.lastname: Clausen
authors.forename: Egon
authors.initials: E
authors.lastname: Persson
authors.forename: Mirella
authors.initials: M
authors.lastname: Ezban
authors.forename: Jørgen
authors.initials: J
authors.lastname: Ingerslev
authors.forename: Benny
authors.initials: B
authors.lastname: Sørensen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005167:Factor VII / Q000627:therapeutic use*; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D010974:Platelet Aggregation; D011994:Recombinant Proteins / Q000627:therapeutic use; D013916:Thrombelastography; D013917:Thrombin / Q000032:analysis; D013921:Thrombocytopenia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome; D014914:Whole Blood Coagulation Time
chemical_list: D006490:Hemostatics; C519901:NN1731; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin