Arterial Thrombosis in Mice with Factor V Leiden Mutation

Abstract

The factor V Leiden (FVL) mutation has been demonstrated to be associated with the development of venous thrombosis in humans. Whether such a propensity also exists in the arterial circulation remains controversial. In an effort to minimize the variability that clouds the clinical study of arterial thrombosis, we studied FVL-associated arterial thrombosis in an experimental model of homozygous, heterozygous, and wild-type mice. Heterozygous FVL mice were crossbred to C57BL/6J mice over several generations. The genotypes of the resulting three genotype groups (wild type, heterozygous FVL, and homozygous FVL) were blinded to the investigators. Arterial injury was produced with the injection of ferric chloride into an isolated segment of carotid artery. Arterial thrombosis was assessed with an ultrasonic flow probe and the time to occlusion (TTO) was recorded. The carotid artery occluded within 60 minutes of injury in 72 of the animals studied (97.3%). The carotid artery remained patent at 60 minutes in the remaining two animals, both of whom were subsequently found to be genotypically wild type. There was a statistically significant relationship between TTO and genotype (p = .002). TTO was greatest in the wild-type mice (p < .001 vs heterozygous, < .001 vs homozygous) and least in the homozygotes (p < .001 vs heterozygotes). Increased thrombogenicity is present in mice with the FVL mutation and is more prolonged in homozygotes than heterozygotes. These findings provide some corroboration to the clinical studies that suggest an increased risk of arterial events in patients with the FVL mutation.

Factor V Leiden Mutation in Reocclusion After Intra-Arterial Thrombolysis

“…In animal studies, Sampram et al 11 found that the carotid arteries occluded within 60 minutes of injury in 97.3% of mice with Factor V Leiden mutation, homozygous occluding faster than heterozygous. Cooley et al 12 also demonstrated a higher propensity for arterial occlusion in homozygotes than in wild mice.…”