Evidence map›Paper›PMID 30952675›Full record

ArticleBlood2019

Red blood cells modulate structure and dynamics of venous clot formation in sickle cell disease.

Camille Faes, Anton Ilich, Amandine Sotiaux, Erica M Sparkenbaugh, Michael W Henderson, Laura Buczek, Joan D Beckman, Patrick Ellsworth, Denis F Noubouossie, Lantarima Bhoopat and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Red blood cell-derived transglutaminase 2 influences thrombus formation.Research and practice in thrombosis and haemostasis · 2026
    Article
  4. When sickle cell trait is not just trait: risk of VTE.Hematology. American Society of Hematology. Education Program · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Observational
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Blood clot contraction: Mechanisms, pathophysiology, and disease.Research and practice in thrombosis and haemostasis · 2023
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 2 countries.

Camille FaesDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.ORCID 0000-0001-7047-2482
Anton IlichDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.ORCID 0000-0002-7669-0760
Amandine SotiauxDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Erica M SparkenbaughDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Michael W HendersonDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Laura BuczekDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Joan D BeckmanDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.ORCID 0000-0001-7903-944X
Patrick EllsworthDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Denis F NoubouossieDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Lantarima BhoopatDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Mark PiegoreDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Céline RenouxInteruniversity Laboratory of Human Movement Biology EA7424, University Lyon-University Claude Bernard Lyon 1, Villeurbanne, France.
Wolfgang BergmeierDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Yara ParkDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Kenneth I AtagaDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Brian CooleyDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Alisa S WolbergDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.ORCID 0000-0002-2845-2303
Nigel S KeyDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Rafal PawlinskiDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
University of North Carolina at Chapel Hill · USUniversité Claude Bernard Lyon 1 · FR

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HONG JIN KIM · 1985 to 2026
$201.5M
Research Training in Hematology at UNC Chapel HillT32HL007149 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Nigel S. Key · 1985 to 2026
$8.6M
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
Fibrinogen and Factor XIII in Venous ThrombosisR01HL126974 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Alisa S. Wolberg · 2016 to 2026
$4.4M
Mechanisms of coagulation-dependent pathologies in sickle cell diseaseR01HL142604 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PAWLINSKI, RAFAL L · 2018 to 2021
$1.6M
Factor XIII and Fibrinogen: Mechanisms of Genetic Risk in SCD-Related PriapismR21DK106509 · NIDDK · DUKE UNIVERSITY · PI TELEN, MARILYN J · 2015 to 2016
$445k
NCI NIH HHS P30 CA016086NHLBI NIH HHS R01 HL126974NHLBI NIH HHS R01 HL142604NHLBI NIH HHS T32 HL007149NHLBI NIH HHS U01 HL117659NIDDK NIH HHS R21 DK106509
6 · The paper itself

Abstract

Sickle cell disease (SCD) is associated with chronic activation of coagulation and an increased risk of venous thromboembolism. Erythrocyte sickling, the primary pathologic event in SCD, results in dramatic morphological changes in red blood cells (RBCs) because of polymerization of the abnormal hemoglobin. We used a mouse model of SCD and blood samples from sickle patients to determine if these changes affect the structure, properties, and dynamics of sickle clot formation. Sickling of RBCs and a significant increase in fibrin deposition were observed in venous thrombi formed in sickle mice. During ex vivo clot contraction, the number of RBCs extruded from sickle whole blood clots was significantly reduced compared with the number released from sickle cell trait and nonsickle clots in both mice and humans. Entrapment of sickled RBCs was largely factor XIIIa-independent and entirely mediated by the platelet-free cellular fraction of sickle blood. Inhibition of phosphatidylserine, but not administration of antisickling compounds, increased the number of RBCs released from sickle clots. Interestingly, whole blood, but not plasma clots from SCD patients, was more resistant to fibrinolysis, indicating that the cellular fraction of blood mediates resistance to tissue plasminogen activator. Sickle trait whole blood clots demonstrated an intermediate phenotype in response to tissue plasminogen activator. RBC exchange in SCD patients had a long-lasting effect on normalizing whole blood clot contraction. Furthermore, RBC exchange transiently reversed resistance of whole blood sickle clots to fibrinolysis, in part by decreasing platelet-derived PAI-1. These properties of sickle clots may explain the increased risk of venous thromboembolism observed in SCD.

Indexed as

Anemia, Sickle CellAnimalsErythrocytesErythrocytes, AbnormalHumansMiceThrombosisVenous Thrombosis

Identifiers

PMID30952675
PMCPMC6557624
OpenAlexW2926022927

What Socratic holds

Textmetadata
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 Socratic graph.