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Background This study evaluated E-selectin inhibition with GMI-1271 (Uproleselan [GMI]) alone and in combination with the standard of care low-molecular-weight heparin (LMWH) to improve vein recanalization, decrease vein wall inflammation and protect against adverse bleeding in a primate model. We sought to examine this novel treatment of venous thrombosis. Methods Using a well-documented primate animal model, iliac vein thrombosis was induced by balloon occlusion of the iliac vein for 6 hours. Starting on day 2 after thrombosis, animals began treatment in two phases. In phase one, nontreated controls received no treatment (n = 5) vs animals treated with the E-selectin inhibitor GMI, 25 mg/kg, subcutaneous (SC), once daily (n = 4) for 21 days (previously published data). In phase two, animals were treated with GMI plus a combination of LMWH 1.5 mg/kg or 40 mg (GMI + LMWHc) SC once daily (n = 8) for 19 days; and animals treated with LMWH 1.5 mg/kg or 40 mg (LMWHc) SC once daily (n = 6) for 19 days. Animals were evaluated by magnetic resonance venography for vein recanalization and inflammation by gadolinium extravasation, duplex ultrasound, coagulation tests (thromboelastography, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen) and complete blood count at baseline, days 2, 7, 14, and 21 at euthanasia. Statistical analysis included using unpaired t test with Welch's correction for direct comparisons and one-way analysis of variance for comparison between the groups. Results Percent vein recanalization by magnetic resonance venography was highest in the GMI alone group followed by GMI + LMWHc, both significantly different from control. On ultrasound examination, animals treated with GMI alone had no decrease in open vein lumen by day 21, whereas decreases were observed in groups GMI + LMWHc (–26%), LMWHc (–27%), and controls (–80%). Vein wall inflammation decreased significantly in all treated groups. Intimal fibrosis and intimal thickness was best preserved in the GMI alone group. An analysis of total vein wall collagen revealed a trend in all treatment groups of decreasing vein wall collagen. No clinically significant bleeding events were noted in any group. The LMWH groups trended to have prolonged coagulation test values, whereas E-selectin inhibition with GMI did not cause clinically significant changes in coagulation measures. Conclusions Treatment with E-selectin inhibition results in improved vein recanalization, a decrease in vein wall inflammation and vein wall intimal thickness and fibrosis, with no changes in markers of coagulation. E-selectin inhibition with GMI alone is superior to E-selectin inhibition combined with LMWH, LMWH alone, and no treatment in this deep vein thrombosis model of iliac vein thrombosis.

Background The aim of the present study was to investigate the changes in pressure over time under three different compression bandages and compare the temporal patterns of pressure changes among them. Methods The 4-hour changes in interface pressure were investigated in 10 volunteers with no venous disease or leg swelling. In 20 patients with venous ulcers, the change in interface pressure was measured after 4 hours, 1 day, and 7 days of bandage wearing. The three bandages tested were the Smart Sleeve compression system (SSB; Carolon, Rural Hall, NC), Coban 2 (C2; 3M, St Paul, Minn), and Profore Lite (PL; Smith & Nephew, London, United Kingdom). Pressure measurements were performed using the PicoPress transducer (Microlab, Padua, Italy) and the Juzo Pressure Monitor (Juzo, Cuyahoga Falls, Ohio). Results In the 10 volunteers, the mean pressure loss during the first 4 hours under the SSB, C2, and PL were 4.5, 3.7, and 6.6 mm Hg, respectively. No significant differences were seen in the pressure loss among the three bandages, whether in the supine (P = .59) or standing (P = .47) position. In the 20 patients with venous ulcers, the pressure had decreased gradually over 7 days under the C2 bandages. For the SSB and PL bandages, however, the interface pressure was relatively stable during the first day but decreased significantly afterward. The mean pressure loss during the 7 days was 4.7, 7.7, and 8.6 mm Hg for the SSB, PL, and C2, respectively (P = .017). Only the SSB maintained a desirable mean pressure >30.0 mm Hg on the seventh day in the patients with venous ulcers. Conclusions The interface pressure had decreased over time under all three studied bandages. However, the temporal pattern of the pressure changes varied among the different bandages. Therefore, monitoring the interface pressure, allowing for adjustment or changes of the bandage at an accurate point, is essential to maintain a desirable interface pressure during compression therapy.