Abstract 157: Role Of Systemic Platelet Levels In Venous Thrombosis And Resolution In A Murine Model Of Inferior Vena Cava Constriction

Background: Platelet role in primary clot formation in response to vessel wall injury is well established; however, the role of systemic platelet levels in deep vein thrombosis (DVT) and its sequelae is unclear. Their interaction with the venous endothelium under low shear stress, regulation of thrombosis, and mediation of both innate and adaptive immune responses through selectin and toll-like receptor expression, respectively, warrants further investigation into their role in DVT formation and resolution. In this study, we present a role for systemic platelet levels in regulating thrombus resolution. Methods: Wildtype, male or female CD1 mice were treated with a thrombopoietin antisense oligonucleotide (TPO-ASO) at 10 mg/kg, eltrombopag at 75 mg/ kg, saline (control), or a scrambled TPO-ASO (control) at 8 mg/ kg prior to surgical creation of a venous thrombus by ligation of the infra-renal inferior vena cava (IVC). Peak scaled thrombus weights (i.e., linear density measured using a ratio of the clot and IVC weight scaled to the length of the IVC) were measured to characterize the early resolution of the thrombus through involution and recanalization. Mice were euthanized on postoperative days 3 and 7 to measure the formation and resolution of the thrombus, respectively. Results: Platelet levels were elevated and decreased by over 30% by the day of surgical treatment after TPO-ASO and eltrombopag treatments, respectively. Scaled thrombus weights were significantly different (p = 0.045, Kruskal Wallis) between groups on day 7 after IVC constriction. Post-hoc analysis (Dunn Test with Benjamini-Hochberg correction) revealed that the TPO-ASO group (mean = 25.4 +/- 0.9 mg/cm) had significantly decreased (p = 0.018) scaled thrombus weights compared to the mice treated with eltrombopag (mean = 35.3 +/- 6.5 mg/cm) on day 7. Thrombus formation on day 3 was not statistically different between treatment groups. Conclusion: Achieving a minimum threshold of 30% reduction of systemic platelet levels by TPO-ASO enhanced thrombus resolution, but not thrombus formation, in our stasis model of rodent DVT resolution. These data suggest a potential role for systemic platelet levels in regulating thrombus resolution.