Anzeige
Anzeige

Archive

The in vitro effect of the new antithrombotic drug candidate ALX-0081 on blood samples of patients undergoing percutaneous coronary intervention

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH10-12-0804
Issue: 2011: 106/1 (July) pp. 1-184
Pages: 165-171

The in vitro effect of the new antithrombotic drug candidate ALX-0081 on blood samples of patients undergoing percutaneous coronary intervention

J. E. van Loon (1), P. P. T. de Jaegere (2), H. Ulrichts (3), H. H. D. M. van Vliet (1), M. P. M. de Maat (1), P. G. de Groot (4), M. L. Simoons (2), F. W. G. Leebeek (1)

(1) Department of Haematology, Erasmus Medical Center Rotterdam, the Netherlands; (2) Department of Cardiology, Erasmus Medical Center Rotterdam, the Netherlands; (3) IRC, Laboratory for Thrombosis Research, KU Leuven, Leuven, Belgium; (4) Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, the Netherlands

Keywords

von Willebrand factor, Antithrombotic drugs, ALX-0081, PTCA

Summary

Compound ALX-0081 is a bivalent humanised Nanobody® that binds the A1-domain of von Willebrand factor (VWF) with high affinity. Consequently, it can block the interaction between VWF and its platelet-receptor-glycoprotein Ib, which leads inevitably to formation of arterial thrombi. It was the objective of this study to assess the in vitro effects of ALX-0081 on platelet adhesion and aggregation in coronary artery disease (CAD) patients to determine the optimal concentration of ALX-0081 and the effect of co-medication. We included nine CAD patients, who were scheduled for elective percutaneous coronary intervention (PCI), and 11 healthy volunteers. At admission all patients received aspirin, clopidogrel and heparin. Blood was drawn 24 hours (h) before and 1 h after start of the PCI procedure and was subsequently spiked with different concentrations of ALX-0081 or buffer. The efficacy of ALX-0081 was assessed by in vitro experiments: flow chamber experiments, ristocetin-induced platelet aggregation (RIPA), and the platelet function analyser (PFA-100™). VWF levels in CAD patients were significantly higher than in healthy controls. During PCI VWF levels did not rise. In all in vitro experiments, ALX-0081 led to complete inhibition of platelet adhesion and aggregation. However, the required effective concentration was higher in patients than in controls and was related to plasma VWF levels. In conclusion, ALX-0081 is able to completely inhibit in vitro platelet adhesion and aggregation in CAD patients scheduled for elective PCI. The efficacy of ALX-0081 is not influenced by PCI or co-medication. However, due to higher VWF levels in CAD patients a higher effective concentration of ALX-0081 was required than in healthy individuals.

You may also be interested in...

1.
Masahito Uemura1*, Yoshihiro Fujimura2*, Masanori Matsumoto 2, Hiromichi Ishizashi 2, Seiji Kato 2, Tomomi Matsuyama 1, Ayami Isonishi 2, Masatoshi Ishikawa 1, Masato Yagita 4, Chie Morioka 1, Hitoshi Yoshiji 1, Tatsuhiro Tsujimoto 1, Norio Kurumatani 3, Hiroshi Fukui1

Thromb Haemost 2008 99 6: 1019-1029

https://doi.org/10.1160/TH08-01-0006

2.
Marjolijn van Lier 1, Sandra Verhoef 1, Sandra Cauwenberghs 2, Johan W. M. Heemskerk 2, Jan-Willem N. Akkerman 1, Harry F. G. Heijnen1,3

Thromb Haemost 2008 99 6: 1068-1078

https://doi.org/10.1160/TH07-08-0528

3.

Steven W. Pipe

Thromb Haemost 2008 99 5: 840-850

https://doi.org/10.1160/TH07-10-0593