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	Ole H Larsen, Niels Clausen, Egon Persson, Mirella Ezban, Jørgen Ingerslev, Benny Sørensen
Journal	British journal of haematology (Br J Haematol) Vol. 144 Issue 1 Pg. 99-106 (Jan 2009) ISSN: 1365-2141 [Electronic] England
PMID	19016728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Hemostatics NN1731 Recombinant Proteins Factor VII recombinant FVIIa Factor VIIa Thrombin
Topics	Adolescent Child Child, Preschool Factor VII (therapeutic use) Factor VIIa (therapeutic use) Female Hemostatics (therapeutic use) Humans Infant Male Platelet Aggregation Recombinant Proteins (therapeutic use) Thrombelastography Thrombin (analysis) Thrombocytopenia (blood, drug therapy, physiopathology) Treatment Outcome Whole Blood Coagulation Time

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!