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

Janine E. van Loon; Peter P. T de Jaegere; Huub H. D. M van Vliet; Moniek P. M de Maat; Philip G. de Groot; Maarten L. Simoons; Frank W. G. Leebeek

doi:10.1160/TH10-12-0804

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(01): 165-171
DOI: 10.1160/TH10-12-0804

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

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

Authors

Janine E. van Loon

¹Department of Haematology, Erasmus Medical Center Rotterdam, the Netherlands
Peter P. T de Jaegere

²Department of Cardiology, Erasmus Medical Center Rotterdam, the Netherlands
Huub H. D. M van Vliet

¹Department of Haematology, Erasmus Medical Center Rotterdam, the Netherlands
Moniek P. M de Maat

¹Department of Haematology, Erasmus Medical Center Rotterdam, the Netherlands
Philip G. de Groot

⁴Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, the Netherlands
Maarten L. Simoons

²Department of Cardiology, Erasmus Medical Center Rotterdam, the Netherlands
Frank W. G. Leebeek

¹Department of Haematology, Erasmus Medical Center Rotterdam, the Netherlands

Abstract

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^TM). 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.

ALX-0081 - antithrombotic drugs - von Willebrand Factor - PTCA

Full Text

References

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