Abstract Number: PB2486
Meeting: ISTH 2020 Congress
Background: This study evaluated E-selectin inhibition with GMI-1271 alone and in combination with standard of care low-molecular-weight heparin (LMWH).
Aims: To improve vein recanalization, decrease vein wall inflammation and protect against adverse bleeding in a primate model.
Methods: Utilizing a well-documented primate animal model, Iliac vein thrombosis was induced by balloon occlusion of the iliac vein for 6 hours. Starting on post-thrombosis day 2, animals began treatment in two phases. In phase one, non-treated controls (CTR) received no treatment (n=5) versus animals treated with the E-selectin inhibitor GMI-1271 (GMI), 25 mg/kg, SC, once daily (n=4) for 21 days [results in-press JVS VL]. In Phase 2, animals were treated with GMI-1271 plus a combination of LMWH 1.5 mg/kg or 40 mg (GMI + LMWHc), SC, once daily (n=8) for 21 days; and animals treated with LMWH 1.5 mg/kg or 40 mg (LMWHc), SC once daily (n=6) for 21 days. Animals were evaluated by magnetic resonance venography (MRV) for vein recanalization and inflammation by gadolinium (Gd) extravasation, duplex ultrasound, coagulation tests (thromboelastography, bleeding time, PT, aPTT, fibrinogen) and CBC at baseline, days 2, 7, 14, and 21 at euthanasia.
Results: Percent vein recanalization by MRV was best in the GMI group followed by GMI + LMWHc (both p< 0.05 vs. CTR, Figure 1A). Vein wall inflammation decreased significantly in all groups (Figure 1B). By ultrasound, animals treated with GMI had no decreased vein opening by day 21, while groups GMI + LMWHc group decreased (-26%), LMWHc (-27%), and CTR (-80%). No clinically significant bleeding events were noted in any group. The LMWH groups trended to have prolonged coagulation test values while E-selectin inhibition with GMI did not cause clinically significant changes in coagulation measures.
Conclusions: E-selectin inhibition with GMI-1271 alone is superior to E-selectin inhibition combined with LMWH, LMWH alone and no treatment in this DVT model.
To cite this abstract in AMA style:Myers D, Jr , Ning J-, Lester P, Adili R, Hawley A, Durham L, Dunivant V, Reynolds G, Crego K, Sood S, Sigler R, Fogler W, Magnani J, Holinstat M, Wakefield T. E-selectin Inhibitor Is Superior to LMWH for Treatment of Experimental Venous Thrombosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/e-selectin-inhibitor-is-superior-to-lmwh-for-treatment-of-experimental-venous-thrombosis/. Accessed May 18, 2021.
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