Factor VIIa analogue (V158D/E296V/M298Q‐FVIIa) normalises clot formation in whole blood from patients with severe haemophilia A

British Journal of Haematology - Tập 137 Số 2 - Trang 158-165 - 2007
Benny Sørensen1, Egon Persson2, Jørgen Ingerslev1
1Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Skejby, Aarhus N
2Haemostasis Biochemistry, Novo Nordisk A/S, Måløv, Denmark

Tóm tắt

SummaryThis 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.

Từ khóa


Tài liệu tham khảo

10.1111/j.1538-7836.2004.00759.x

10.1161/01.ATV.0000042081.57854.A2

10.1046/j.1538-7836.2003.00181.x

10.1182/blood.V91.12.4581

10.1016/0140-6736(92)90874-3

10.1093/bja/aei052

10.1016/S0037-1963(01)90140-4

10.1080/00365510600672783

10.1016/0140-6736(91)90729-9

10.1046/j.1365-2516.2003.00767.x

10.1159/000056704

10.1046/j.1538-7836.2003.00444.x

10.1016/0140-6736(92)91324-2

Martinowitz U., 2005, Concomitant infusion of low doses of rFVIIa and FEIBA in severe haemophilia A patients with an inhibitor to factor VIII who are refractory to rFVIIa or FEIBA has an excellent haemostatic effect and synergistically enhances thrombin generation, Journal of Thrombosis and Haemostasis, 3, P0637

10.1046/j.1432-1033.2002.03323.x

10.1074/jbc.M102187200

10.1073/pnas.241339498

10.1042/BJ20031596

10.1111/j.1538-7836.2005.01373.x

10.1182/blood.V88.9.3432.bloodjournal8893432

10.1111/j.1538-7836.2005.01513.x

10.1046/j.1365-2516.1999.00300.x

10.1111/j.1365-2516.2004.00912.x

Sørensen B., 2003, Potential effect of recombinant factor VIIa in ex vivo reversal of pentasaccharide induced anticoagulation, Journal of Thrombosis and Haemostasis, 1, P1108

10.1111/j.1538-7836.2004.00528.x

10.1053/j.seminhematol.2003.11.024

10.1111/j.1365-2516.2005.01156.x

10.1046/j.1538-7836.2003.00075.x

10.1097/00001721-200307000-00007

10.1093/bja/aei557

Sørensen B., 2005, What the standard APTT didn't tell you – dynamic plasma clotting parameters reveal hypercoagulation, Blood, 106, 739, 10.1182/blood.V106.11.2634.2634

10.1182/blood-2003-05-1369

10.1182/blood-2004-03-1042

10.1046/j.1365-2516.2003.00780.x

Thông tin
Thông tin xuất bản

British Journal of Haematology

Tập 137 Số 2

158-165

Thông tin tác giả