A novel hollow flexible wire allows the safe and effective local application of thrombolytic therapy in a mouse model of deep vein thrombosis

Abstract

Purpose: Severe cases of deep vein thrombosis (DVT) may require thrombolysis in order to prevent further complications such as embolism, postthrombotic syndrome, or edema. Moreover, patients with thrombotic occlusion of small vessels of the eye or brain may benefit from a precisely guided application of local thrombolytic therapy. Small veins are particularly fragile and require gentle means of local drug infusion to avoid vessel wall perforation. Here, we introduce a new way of thrombolysis therapy application using a hollow flexible wire. Aims: To test the feasibility of local thrombolytic therapy via hollow flexible wire in a mouse model of DVT. Methods: Inferior vena cava (IVC) thrombosis was induced in C57Bl/6 mice by vessel wall exposure to a filter paper saturated with 10% ferric chloride for 15 minutes after laparatomy in anesthesized mice. Thrombus formation was visualized by intravital microscopy of rhodamine-labeled platelets and leukocytes. A nitinol hypotube coronary wire with perforated platinum tip was inserted via a 0,8 x 40 mm canula into the IVC lumen distal to the site of ferric chloride exposure. Either tPA (alteplase, 1.5mg/kg) or saline (control) was administered for 1 minute via the platinum wire without mechanical fragmentation of the thrombus. Thrombus size was assessed by immunohistochemistry (platelet CD41 staining). Results: Intravital microscopy of the ferric chloride-exposed IVC depicted platelet-containing thrombus growth until initiation of local thrombolytic treatment. Alteplase administration resulted in the resolution of thrombi within 2-5 minutes. Histology revealed a marked decrease in thrombus size in IVC cross-sections of alteplase-treated mice (22.7%±0.9% vein occlusion as compared to 85.6%±7.5% vein occlusion in saline treated mice). Bleeding complications were not increased in alteplase treated mice. Conclusions: We demonstrate that a flexible hollow wire enables the successful application of thrombolytic therapy to IVC thrombi in mice without vessel wall perforation. Flexible wire based-thrombolytic therapy appears to be a safe and reliable method for thrombus dissolution in fragile small veins. Wire-based thrombolytic therapy may become a promising strategy in the management of small vessel thrombosis and may improve targeted therapy.