Murine strain differences in hemostasis and thrombosis and tissue factor pathway inhibitor

Introduction: Differences among murine strains often lead to differential responses in models of human disease. The aim of the current study was to investigate whether differences exist among strains in models of hemostasis and thrombosis and whether these differences are reflected in differences in the tissue factor (TF) pathway.

Methods: We examined baseline hemostatic parameters and the response to FeCl3-induced arterial thrombosis and a tail vein bleeding model in C57BL/6J (C57), 129S1/SvImJ (129S), and Balb/cJ (BalbC) mice. Finally, we examined TF and tissue factor pathway inhibitor (TFPI) activities in blood and expression in vascular tissue to determine whether these factors covary with a thrombotic phenotype.

Results: No differences were observed in PT or aPTT among strains. 129S mice had lower platelet counts (p<0.001). BalbC had an increased rate of occlusion (mean occlusion time of 330+/-45 sec) in a FeCl(3)-induced model of thrombosis when compared to C57 (1182+/-349 sec) or 129 S (1442+/-281 sec) (p<0.05). Similarly, BalbC demonstrated reduced blood loss in tail bleeding experiments when compared to C57 and 129S. Vascular expression of TF and TFPI content did not correlate with the thrombotic phenotype of BalbC. However, circulating TFPI activities were lower in BalbC compared to both C57 and 129S mice. When normalized to circulating TF activities, BalbC had lower circulating TFPI activity than C57 and 129S, and there was a significant correlation between tail bleeding and normalized TFPI activity (r=0.67).

Conclusions: These data suggest that there are significant differences among strains in thrombosis and hemostasis and that circulating TFPI activity correlates with these differences.