British journal of haematology
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A new anticoagulant system involving a serpin has been recently characterised. The protein Z/Z-dependent protease inhibitor (PZ/ZPI) system inhibits activated factors X, XI and IX by different mechanisms. By homology with other anticoagulant systems (antithrombin or the protein C/protein S), deficiency of the serpin (ZPI) or its cofactor (PZ) might imbalance the haemostatic system with thrombotic consequences. ⋯ Finally, some reports suggest that PZ deficiency might increase the risk of thrombosis. However, other studies question the thrombotic relevance of both ZPI and PZ deficiencies. This system could play a redundant role in haemostasis that explains the conflicting results on its thrombotic potential, which might be exacerbated in combination with other prothrombotic factors.
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Comparative Study
Factor VIIa analogue (V158D/E296V/M298Q-FVIIa) normalises clot formation in whole blood from patients with severe haemophilia A.
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. ⋯ 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.