Summary
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.
Keywords
Thrombus - coagulation - Factor V Leiden - fibrin - heparin
