Co-Inheritance of FV Leiden and High Levels of FIX Results in Novel Models for Thrombophilia and Spontaneous Fetal Loss

• Published in: Blood 2005-11, Vol.106 (11), p.1946-1946
• Main Authors: Freguia, Christian Furlan, Schuettrumpf, Joerg, Baila, Stefano, Liu, Jianhua, Bunte, Ralph, Camire, Rodney M., Arruda, Valder R.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V106.11.1946.1946

High levels of FIX is emerging as a risk factor for spontaneous venous thrombosis, affecting ~20% of unselect patients and increasing rates of recurrent thromboembolic events. We have generated mice expressing supraphysiological levels of human FIX (up to 400% of normal) but these animals did not develop thrombosis. Therefore, we decided to test whether an additional risk for thrombosis would trigger a prothrombotic phenotype in these mice. Because the FVL mutation is also present in 20% of thrombophilia subjects, we chose FVL mice as model. Breedings included both parents being heterozygous FVL(+/−) but only one was transgenic for FIX (tFIX: 4–8μg/ml plus the endogenous murine FIX). All mice were on C57Bl/6 background. More than 200 newborns were obtained but surprisingly no animal of FVL(+/+)/tFIX genotype was identified. When pregnancies were interrupted at embryonic age of E9.5 to E16.5, no deviation from the expected/observed embryos genotypes was observed. However, the number of reabsorbed embryos increased significantly from 13% (E9.5) to 33% (E.16.5), p