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Factor VIIa analogue (V158D/E296V/M298Q‐FVIIa) normalises clot formation in whole blood from patients with severe haemophilia A
Author(s) -
Sørensen Benny,
Persson Egon,
Ingerslev Jørgen
Publication year - 2007
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.1365-2141.2007.06534.x
Subject(s) - thromboelastography , recombinant factor viia , haemophilia a , medicine , haemophilia , tissue factor , coagulation , hemostasis , whole blood , surgery
Summary This study evaluated and compared the haemostatic potential of a recombinant factor VIIa (rFVIIa) analogue (V158D/E296V/M298Q‐FVIIa, NN1731, Novo Nordisk, Denmark) with rFVIIa (NovoSeven ® , Novo Nordisk). In vitro studies were performed using freshly drawn whole blood (WB) from 14 patients with severe haemophilia A and two patients with inhibitory antibodies to FVIII, comparing NN1731 and rFVIIa against a buffer control. Fourteen healthy males served as controls. Dynamic WB coagulation profiles were recorded, quantitatively illustrating the initiation [clotting time = CT (s)], propagation [maximum velocity = MaxVel (mm*100/s)] and termination [maximum clot firmness = MCF (mm*100)] as determined by thromboelastography with minute amounts of tissue factor (TF, Innovin ® – final dilution 1:50 000, c. 0·12 pM) serving as activator. WB clot stability was assessed using a separate set‐up including TF plus tissue plasminogen activator (final concentration 2 nmol/l), evaluating the MCF as well as the area under the elasticity curve (AUEC) after 60 min (mm*100*s). NN1731 shortened the CT more markedly than rFVIIa. At the dose tested, NN1731 even shortened CT in haemophilia below the value of healthy males. NN1731 accelerated MaxVel giving a value indistinguishable from that in healthy males. Furthermore, NN1731 increased clot stability more markedly than rFVIIa. Altogether, these in vitro studies on WB revealed a favourable haemostatic potential of NN1731 compared with rFVIIa in severe haemophilia A, both in the absence and presence of enhanced fibrinolytic activity.