Evidence map›Paper›PMID 28932824›Full record

ArticleBlood advances2017

Factor VIIa interaction with EPCR modulates the hemostatic effect of rFVIIa in hemophilia therapy: Mode of its action.

Shiva Keshava, Jagan Sundaram, Anuradha Rajulapati, Charles Esmon, Usha Pendurthi, L Vijaya Mohan Rao

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

Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
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  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
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  12. The evolution of factor VIIa in the treatment of bleeding in haemophilia with inhibitors.Haemophilia : the official journal of the World Federation of Hemophilia · 2019
    Review
  13. Article
  14. Article
  15. Diagnostic Values of Inflammatory and Angiogenic Factors for Acute Joint Bleeding in Patients With Severe Hemophilia A.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Article
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

6 authors at 2 institutions in 1 country.

Shiva KeshavaDepartment of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX.
Jagan SundaramDepartment of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX.
Anuradha RajulapatiDepartment of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX.
Charles EsmonCoagulation Biology Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Usha PendurthiDepartment of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX.
L Vijaya Mohan RaoDepartment of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX.
The University of Texas Health Science Center at Tyler · USOklahoma Medical Research Foundation · US

Funding

Analysis and Characterization of Trauma-Induced CoagulopathyUM1HL120877 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI MORRISSEY, JAMES H., WISNIEWSKI, STEPHEN R · 2013 to 2019
$26.6M
Factor VIIa Interaction with Endothelial Cell Protein C ReceptorR01HL107483 · NHLBI · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · PI LELLA, VIJAYA MOHAN RAO · 2012 to 2019
$2.9M
NHLBI NIH HHS R01 HL107483NHLBI NIH HHS UM1 HL120877
6 · The paper itself

Abstract

Recent studies established that clotting factor VIIa (FVIIa) binds endothelial cell protein C receptor (EPCR). It has been speculated that FVIIa interaction with EPCR might augment the hemostatic effect of rFVIIa in therapeutic conditions. The present study is carried out to investigate the mechanism by which FVIIa interaction with EPCR contributes to the hemostatic effect of rFVIIa in hemophilia therapy. Active-site inhibited FVIIa, which is capable of binding to EPCR but has no ability to activate factor X, reduced the concentration of rFVIIa required to correct the bleeding following the saphenous vein injury in mouse hemophilia model systems. Higher doses of rFVIIa were required to restore hemostasis in EPCR overexpressing hemophilia mice compared to hemophilia mice expressing normal levels of EPCR. Administration of FVIII antibody induced only mild hemophilic bleeding in EPCR-deficient mice, which was corrected completely with a low dose of rFVIIa. Administration of therapeutic concentrations of rFVIIa increased plasma protein C levels in EPCR overexpressing mice, indicating the displacement of protein C from EPCR by rFVIIa. EPCR levels did not significantly alter the bioavailability of rFVIIa in plasma. Overall, our data indicate that EPCR levels influence the hemostatic effect of rFVIIa in treating hemophilia. Our present findings suggest that FVIIa displacement of anticoagulant protein C from EPCR that results in down-regulation of activated protein C generation and not the direct effect of EPCR-FVIIa on FX activation is the mechanism by which FVIIa interaction with EPCR contributes to the hemostatic effect of rFVIIa in hemophilia therapy.

Identifiers

PMID28932824
PMCPMC5602564
OpenAlexW2731588942

What OpenQuestion holds

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Registered trials

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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.