Increased venous versus arterial thrombosis in the Factor V Leiden mouse.
BACKGROUND
Deep vein thrombosis (DVT) occurs with high prevalence in association with the Factor V Leiden (R506Q) mutation, whereas most evidence suggests no correlation with clinical arterial thrombosis.


OBJECTIVE
This study compared arterial to venous thrombosis in the mutationally analogous Factor V Leiden mouse.


METHODS
Three separate vascular thrombosis models were evaluated in Fv(+/+) (wild-type), Fv(Q/+) (heterozygous) and Fv(Q/Q) (homozygous) Factor V Leiden mice.


RESULTS
In a FeCl(3)-induced arterial thrombosis model, no statistical differences among the three genotypes were found in the time to thrombotic occlusion. In contrast, Fv(Q/+) and Fv(Q/Q) mice demonstrated larger femoral vein thrombi at 30 and 60 min compared to wild-types, with Fv(Q/Q) mice having statistically larger thrombi than both wild-type and Fv(Q/+) mice at 10 and 60 min and 24 h (p<0.05). In a model of thrombotic occlusion following arterial and venous anastomotic repair, both Fv(Q/+) and Fv(Q/Q) mice had higher rates of venous thrombosis than wild-types, but only Fv(Q/Q) homozygotes showed a statistically greater arterial occlusion rate than wild-types.


CONCLUSIONS
The Factor V Leiden mouse demonstrated a greater propensity for venous vs. arterial thrombosis, paralleling clinical epidemiologic findings and supporting its use for research on deep vein thrombosis.
Cooley
Brian C
BC
Department of Orthopaedic Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road Milwaukee, WI 53226, USA. bcooley@mcw.edu
Chen
Chao-Ying
CY
Schmeling
Gregory
G
D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000235:genetics*; D001158:Arteries; D002712:Chlorides; D004195:Disease Models, Animal; D005165:Factor V / Q000235:genetics*; D005290:Ferric Compounds; D005787:Gene Frequency; D005973:Glutamine; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013927:Thrombosis / Q000139:chemically induced / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
D002712:Chlorides; D005290:Ferric Compounds; C095381:factor V Leiden; D005973:Glutamine; D005165:Factor V; D001120:Arginine; C024555:ferric chloride