Abstract Number: PB0128
Meeting: ISTH 2020 Congress
Background: Sepsis has been correlated with increased risk for deep vein thrombosis (DVT), concurrently with increased levels of plasma von Willebrand factor (VWF:Ag), a crucial component of DVT.
Aims: To determine the role of VWF in the murine stenosis model of DVT concurrent with lipopolysaccharide (LPS)-induced sepsis.
Methods: DVTs were induced in wildtype mice by stenosis of the inferior vena cava, followed by intraperitoneal administrations of 0.5mg/kg LPS or vehicle control. Mice were sacrificed at either 1.5h or 24h post-stenosis. Thrombosis incidence was noted after 24h. VWF:Ag, cell-free DNA, and VWF activity were quantified by ELISA, PicoGreen, and collagen-binding assays, respectively. To further elucidate the role of VWF in the thrombogenic process, inhibitory anti-VWF or isotype control antibodies were intravenously administered prior to stenosis. We also employed the Hyperion Mass Imaging System to simultaneously quantify and spatially localize nine thrombus constituents at 1µm resolution.
Results: LPS-treated mice had a significantly higher thrombosis incidence compared to controls (P=0.0453), but without a difference in thrombus weight. Compared to pre-stenosis levels, only the LPS-treated mice showed significantly increased VWF:Ag after 1.5h (P=0.0029). At 24h, both the control and LPS cohorts had increased VWF:Ag (P< 0.0001) and collagen-binding (P< 0.0001). When the consumptive effects of thrombosis were considered, the increased VWF:Ag was only significant in the non-thrombosed LPS cohort compared to the non-thrombosed controls (P=0.0108). No increases in ultra-large VWF multimers were observed during the early time points. Furthermore, the LPS-treated mice had significantly higher plasma levels of cell-free DNA at 24h (P=0.0009). Further analysis using inhibitory antibodies showed that VWF inhibition significantly decreased thrombosis incidence in the LPS cohort (P=0.0198). Finally, Hyperion-derived images demonstrate discrete spatial interactions between thrombus constituents (Figure 1).
Conclusions: The increased levels of VWF:Ag (but not activity nor large multimers) associated with LPS-induced acute inflammation significantly contributes to an enhanced tendency for venous thrombosis.
To cite this abstract in AMA style:Choi SJ, Swystun L, Hindmarch C, Dwyer C, Michels A, Hopman W, Lillicrap D. Increased Levels of von Willebrand Factor Associated with Acute Inflammation Contribute to Enhanced Venous Thrombosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/increased-levels-of-von-willebrand-factor-associated-with-acute-inflammation-contribute-to-enhanced-venous-thrombosis/. Accessed May 6, 2021.
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