Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains

Michal Heger; Johan F. Beek; Nicanor I. Moldovan; Chantal M. A. M. van der Horst; Martin J. C. van Gemert

doi:10.1160/TH04-05-0291

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(02): 242-256
DOI: 10.1160/TH04-05-0291

Review Article

Schattauer GmbH

Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains

A theoretical study

Authors

Michal Heger

¹Laser Center and Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Johan F. Beek

¹Laser Center and Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Nicanor I. Moldovan

²Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA
Chantal M. A. M. van der Horst

³Department of Plastic, Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Martin J. C. van Gemert

¹Laser Center and Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Abstract

Summary

For the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the thresh-old damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.

Keywords

Port wine stains - thrombus organization - neovascularization - endothelial progenitor cells - procoagulant pharmaceuticals

Full Text

References

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