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

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Proteases and Extracellular Environment

DOI: http://dx.doi.org/10.1160/TH04-05-0291
Issue: 2005: 93/2 (Feb) pp. 186-397
Pages: 242-256

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

Michal Heger (1) , Johan F. Beek(1) , Nicanor I. Moldovan(2) , Chantal M. A. M. van der Horst(3) , Martin J. C. van Gemert(1)
(1) Laser Center and (3) Department of Plastic, Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (2) Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio

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.