Abstract 297: FHL2 Deficiency Facilitates Tissue Plasminogen Activator-mediated Thrombolysis Without Further Prolonging Bleeding Time

Abstract

Introduction: A recent study showed a relationship between Four-and-a-half-LIM-domains 2 (FHL2) and venous thromboembolism. Here, we investigated FHL2 deficiency-mediated effects on arterial thrombus formation, tissue plasminogen activator (tPA)-mediated thrombolysis, and bleeding time. Methods: First, arterial thrombosis was induced in twelve-week-old male FHL2 +/+ mice (n=17) and FHL2 -/- mice (n=17) by applying FeCl 3 on the left common carotid artery (CCA) for 10 minutes. To measure thrombus volume at 30 minutes (n=10/group) or 3 hours (n=7/group) after the thrombus induction, microCT imaging was performed after intravenous injection of gold nanoparticles (2mg/kg in 200μL). Second, 32 mice (n=16/group) were treated with intravenous tPA (25 mg/kg) at 30 minutes (n=10/group) or 3 hours (n=6/group) after thrombosis, and microCT imaging was performed at baseline and post-tPA 0.5, 1, 3, and 24 hour time-points. Third, tail-bleeding test was performed with (n=6 and 8, respectively) or without (n=8/group) tPA treatment. Results: Thrombus volume at 30 minutes and 3 hours did not differ significantly between the groups. However, post-tPA 3-hour thrombus volume was significantly lower in FHL2 -/- mice than in FHL2 +/+ mice (71% vs. 46% reduction from the baseline, respectively; p=0.03), when the thrombolytic therapy was initiated at 30 minutes after thrombosis. There were no significant inter-group differences in thrombus volumes when tPA treatment was delayed (ie., started at 3 hours after thrombosis). Lastly, bleeding time did not show significant inter-group differences, regardless of tPA therapy (all p>0.05). Conclusions: FHL2 deficiency does not reduce baseline arterial thrombus volume but facilitates tPA-mediated thrombolysis without prolonging bleeding time in mice.