Evidence map›Paper›PMID 32067728›Full record

ArticleJournal of vascular surgery. Venous and lymphatic disorders2020

A new way to treat proximal deep venous thrombosis using E-selectin inhibition.

Daniel Myers, Patrick Lester, Reheman Adili, Angela Hawley, Laura Durham, Veronica Dunivant, Garrett Reynolds, Kiley Crego, Zoe Zimmerman, Suman Sood and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of vascular surgery. Venous and lymphatic disorders, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Immune cell-mediated venous thrombus resolution.Research and practice in thrombosis and haemostasis · 2023
    Review
  8. P- and E- selectin in venous thrombosis and non-venous pathologies.Journal of thrombosis and haemostasis : JTH · 2022
    Review
  9. Article
  10. Review
  11. Review
  12. Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms.International journal of molecular sciences · 2020
    Review
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Daniel MyersConrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich; Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Mich. Electronic address: ddmyers@umich.edu.
Patrick LesterUnit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Mich.
Reheman AdiliDepartment of Pharmacology, University of Michigan, Ann Arbor, Mich.
Angela HawleyConrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
Laura DurhamConrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
Veronica DunivantConrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
Garrett ReynoldsConrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
Kiley CregoConrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
Zoe ZimmermanDepartment of Pharmacology, University of Michigan, Ann Arbor, Mich.
Suman SoodDivision of Hematology/Oncology, University of Michigan, Ann Arbor, Mich.
Robert SiglerUnit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Mich.
William FoglerGlycoMimetics, Inc, Rockville, Md.
John MagnaniGlycoMimetics, Inc, Rockville, Md.
Michael HolinstatDepartment of Pharmacology, University of Michigan, Ann Arbor, Mich.
Thomas WakefieldConrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
University of Michigan–Ann Arbor · USGlycoMimetics (United States) · US

Funding

NHLBI NIH HHS HHSN268201700004C
6 · The paper itself

Abstract

objectiveThere is an inter-relationship between thrombosis and inflammation. Previously, we have shown the importance of P-selectin in thrombogenesis and thrombus resolution in many preclinical animal models. The role of E-selectin has been explored in rodent models and in a small pilot study of clinical calf vein deep venous thrombosis. The purpose of this study was to determine the role of E-selectin in thrombosis in a primate model of proximal iliac vein thrombosis, a model close to the human condition.

methodsIliac vein thrombosis was induced with a well-characterized primate model. Through a transplant incision, the hypogastric vein and iliac vein branches were ligated. Thrombus was induced by balloon occlusion of the proximal and distal iliac vein for 6 hours. The balloons were then deflated, and the primates recovered. Starting on postocclusion day 2, animals were treated with the E-selectin inhibitor GMI-1271, 25 mg/kg subcutaneously, once daily until day 21 (n = 4). Nontreated control animals received no treatment (n = 5). All animals were evaluated by magnetic resonance venography (MRV); evaluation of vessel area by ultrasound, protein analysis, hematology (complete blood count), and coagulation tests (bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, and thromboelastography) were performed at baseline, day 2, day 7, day 14, and day 21 with euthanasia. In addition, platelet function and CD44 expression on leukocytes were determined.

resultsE-selectin inhibition by GMI-1271 significantly increased vein recanalization by MRV vs control animals on day 14 (P < .05) and day 21 (P < .0001). GMI-1271 significantly decreased vein wall inflammation by MRV with gadolinium vein wall enhancement vs control also on day 14 (P < .0001) and day 21 (P < .0001). The thromboelastographic measure of clot strength (maximum amplitude) showed significant decreases in animals treated with GMI-1271 vs controls at day 2 (P < .05) and day 7 (P < .05). Animals treated with GMI-1271 had significant vessel area increase by day 21 vs controls (P < .05) by ultrasound. Vein wall intimal thickening (P < .001) and intimal fibrosis (P < .05) scores were significantly decreased in GMI-1271-treated animals vs controls. Importantly, no significant differences in hematology or coagulation test results were noted between all groups, suggesting that E-selectin inhibition carries no bleeding potential. GMI-1271 did not affect platelet function or aggregation or CD44 expression on leukocytes. In addition, no episodes of bleeding were noted in either group.

conclusionsThis study suggests that E-selectin modulates venous thrombus progression and that its inhibition will increase thrombus recanalization and decrease vein wall inflammation, without affecting coagulation. The use of an E-selectin inhibitor such as GMI-1271 could potentially change how we treat deep venous thrombosis.

Indexed as

AnimalsAnti-Inflammatory AgentsDisease Models, AnimalE-SelectinFibrinolytic AgentsGlycolipidsIliac VeinPapioSignal TransductionVenous ThrombosisAnti-Inflammatory AgentsE-SelectinFibrinolytic AgentsGlycolipidsuproleselanAnimal modelsCoagulationE-selectin inhibitionGlycomimeticInflammationNonhuman primateVenous thrombosis

Identifiers

PMID32067728
PMCPMC9006622
OpenAlexW3006571769

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.