Evidence map›Paper›PMID 29905377›Full record

ArticleAmerican journal of hematology2018

Red Blood Cell Adhesion to Heme-Activated Endothelial Cells Reflects Clinical Phenotype in Sickle Cell Disease.

Erdem Kucukal, Anton Ilich, Nigel S Key, Jane A Little, Umut A Gurkan

Abstract read
In one paragraph

Article in American journal of hematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

34 citing papers in PubMed, 50 citations in OpenAlex.

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  14. Microfluidic methods to advance mechanistic understanding and translational research in sickle cell disease.Translational research : the journal of laboratory and clinical medicine · 2022
    Review
  15. Article
  16. Rapid degradation of protein tyrosine phosphatase 1B in sickle cells: Possible contribution to sickle cell membrane weakening.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  17. The Effect of Sex-Mismatched Red Blood Cell Transfusion on Endothelial Cell Activation in Critically Ill Patients.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Erdem KucukalDepartment of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH, USA.
Anton IlichDivision of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Nigel S KeyDivision of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Jane A LittleDivision of Hematology/Oncology, Case Western Reserve University, University Hospitals Seidman Cancer Center, Cleveland, OH, USA.
Umut A GurkanDepartment of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-0331-9960
Case Western Reserve University · USUniversity of North Carolina at Chapel Hill · USUniversity Hospitals Seidman Cancer Center · US

Funding

Targeted Anticoagulant Therapy for Sickle Cell DiseaseU01HL117659 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KEY, NIGEL S., MACKMAN, NIGEL · 2013 to 2017
$7.6M
Standardized Monitoring of Cellular Adhesion to Improve Clinical Care in Sickle Cell DiseaseR01HL133574 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI GURKAN, UMUT A., LITTLE, JANE · 2016 to 2020
$2.0M
NHLBI NIH HHS R01 HL133574NHLBI NIH HHS U01 HL117659
6 · The paper itself

Abstract

In sickle cell disease (SCD), 'disease severity' associates with increased RBC adhesion to quiescent endothelium, but the impact on activated endothelium is not known. Increased concentrations of free heme result from intravascular hemolysis in SCD. Heme is essential for aerobic metabolism, and plays an important role in numerous biological processes. Excess free heme induces reactive oxygen species generation and endothelial activation, which are associated with cardiovascular disorders including atherosclerosis, hypertension, and thrombosis. Here, we utilized an endothelialized microfluidic platform (Endothelium-on-a-chip) to assess adhesion of sickle hemoglobin-containing red blood cells (HbS RBCs), from adults with homozygous SCD, to heme-activated human endothelial cells (EC) in vitro. Confluent EC monolayers in microchannels were treated with pathophysiologically relevant levels of heme in order to simulate the highly hemolytic intravascular milieu seen in SCD. RBC adhesion to heme-activated ECs varied from subject to subject, and was associated with plasma markers of hemolysis (LDH) and reticulocytosis, thereby linking those RBCs that are most likely to adhere with those that are most likely to hemolyze. These results re-emphasize the critical contribution made by heterogeneous adhesive HbS RBCs to the pathophysiology of SCD. We found that adhesion of HbS RBCs to heme-activated ECs varied amongst individuals in the study population, and associated with biomarkers of hemolysis and inflammation, age, and a recent history of transfusion. Importantly, the microfluidic approach described herein holds promise as a clinically feasible Endothelium-on-a-chip platform with which to study complex heterocellular adhesive interactions in SCD. This article is protected by copyright. All rights reserved.

Identifiers

PMID29905377
PMCPMC6295270
OpenAlexW2808384893

What OpenQuestion holds

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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.