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Brian C. Cooley, Linda Szema, Chao-Ying Chen, Jeffrey P. Schwab, Gregory Schmeling
A murine model of deep vein thrombosis: characterization and validation in transgenic mice
Deep vein thrombosis (DVT) occurs with high prevalence in association with a number of risk factors, including major surgery, trauma, obesity, bed rest (>5 days), cancer, a previous history of DVT, and several predisposing prothrombotic mutations. A novel murine model of DVT was developed for applications to preclinical studies of transgenically constructed prothrombotic lines and evaluation of new antithrombotic therapies. A transient direct-current electrical injury was induced in the common femoral vein of adult C57Bl/6 mice. A non-occlusive thrombus grew, peaking in size at 30 min, and regressing by 60 min, as revealed by histomorphometric volume reconstruction of the clot. Pre-heparinization greatly reduced clot formation at 10, 30, and 60 min (p < 0.01 versus non-heparinized). Homozygous FactorV Leiden mice (analogous to the clinical FactorV Leiden prothrombotic mutation) on a C57Bl/6 background had clot volumes more than twice those of wild-types at 30 min (0.121 0.018 mm3 vs. 0.052 0.008 mm3, respectively; p < 0.01). Scanning electron microscopy revealed a clot surface dominated by fibrin strands, in contrast to arterial thrombi which showed a platelet-dominated structure. This new model of DVT presents a quantifiable approach for evaluating thrombosis-related murine transgenic lines and for comparatively evaluating new pharmacologic approaches for prevention of DVT.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 94, 09/2005
Pages: 498 - 503