Abstract
Superficial vascular anomalies such as port wine stains are commonly treated by selective photothermolysis (SP). The endovascular laser-tissue interactions underlying SP are governed by a photothermal response (thermocoagulation of blood) and a hemodynamic response (thrombosis). Currently it is not known whether the hemodynamic response encompasses both primary and secondary hemostasis, which platelet receptors are involved, and what the SP-induced thrombosis kinetics are in low-flow venules. To (1) define the role and kinetics of primary and secondary hemostasis in laser-induced thrombus formation and (2) determine which key platelet surface receptors are involved in the hemodynamic response. 532-nm laser-irradiated hamster dorsal skin fold venules were studied by intravital fluorescence microscopy following fluorescent labeling of platelets with 5(6)-carboxyfluorescein. Heparin and fluorescently labeled anti-glycoprotein Ib-α (GPIbα) and anti-P-selectin antibodies were administered to investigate the role of coagulation and platelet receptors, respectively. Lesional sizes were quantified by software. Laser irradiation consistently produced sub-occlusive thermal coagula. Thrombosis was triggered in all irradiated venules in a thermal coagulum-independent manner and peaked at 6.25min post-irradiation. Heparin decreased the maximum thrombus size and caused thrombosis to reach a maximum at 1.25min. Immunoblocking of GPIbα abated the extent of thrombosis, whereas immunoblocking of P-selectin had no effect. The hemodynamic response ensues the photothermal response in a thermal coagulum-independent manner and involves primary and secondary hemostasis. Primary hemostasis is mediated by constitutively expressed GPIbα but not by activation-dependent P-selectin.
Highlights
Selective photothermolysis (SP) is a standard treatment modality for superficial vascular anomalies such as port wine stains (PWS) and other vessel-related dermatological disorders [1]
A laser-mediated vascular injury model was employed with which the photothermal and hemodynamic response could be concomitantly studied in refractory PWS vessel analogues by intravital fluorescence microscopy
We demonstrated that (1) secondary hemostasis is triggered by SP, (2) primary and secondary hemostasis occur in the absence of a thermal coagulum, (3) CD42b is involved in the adhesion of platelets at the site of laser irradiation under low flow conditions, (4) the adhesion of platelets at the site of laser irradiation is accompanied by platelet activation, and (5) CD62P does not mediate platelet adhesion during the hemodynamic response
Summary
Selective photothermolysis (SP) is a standard treatment modality for superficial vascular anomalies such as port wine stains (PWS) and other vessel-related dermatological disorders [1]. Alternative treatment strategies are needed to improve therapeutic outcomes in the poorly-to-non-responsive PWS patient population [9]. Superficial vascular anomalies such as port wine stains are commonly treated by selective photothermolysis (SP). The endovascular laser–tissue interactions underlying SP are governed by a photothermal response (thermocoagulation of blood) and a hemodynamic response (thrombosis) It is not known whether the hemodynamic response encompasses both primary and secondary hemostasis, which platelet receptors are involved, and what the SP-induced thrombosis kinetics are in low-flow venules. Objectives: To (1) define the role and kinetics of primary and secondary hemostasis in laser-induced thrombus formation and (2) determine which key platelet surface receptors are involved in the hemodynamic response. Primary hemostasis is mediated by constitutively expressed GPIba but not by activation-dependent P-selectin
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