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Whole blood coagulation in children with thrombocytopenia and the response to platelet replacement, recombinant factor VIIa, and a potent factor VIIa analogue
Author(s) -
Larsen Ole H.,
Clausen Niels,
Persson Egon,
Ezban Mirella,
Ingerslev Jørgen,
Sørensen Benny
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07439.x
Subject(s) - recombinant factor viia , coagulation , platelet , tissue factor , medicine , thromboelastography , coagulopathy , factor vii , thrombin , whole blood , hemostasis , pharmacology , immunology , anesthesia
Summary 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 × 10 9 /l), recombinant factor VIIa (rFVIIa – NovoSeven ® ), and a potent rFVIIa analogue (NN1731) both at 1 and 4 μg/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.