Evidence map›Paper›PMID 38815755›Full record

ArticleJournal of thrombosis and haemostasis : JTH2024

Concizumab improves clot formation in hemophilia A under flow.

Megan P Jewell, Zaina Ashour, Christine H Baird, Marilyn Manco Johnson, Beth Boulden Warren, Adam R Wufsus, Chiara Pallini, Michael Dockal, Marianne Kjalke, Keith B Neeves

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Evaluating the Safety and Efficacy of Concizumab in Hemophilia A/B Patients: A Systematic Review.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Pooled it
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

10 authors.

Megan P JewellDepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
Zaina AshourDepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
Christine H BairdDepartment of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA; Hemophilia and Thrombosis Center, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Marilyn Manco JohnsonDepartment of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA; Hemophilia and Thrombosis Center, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Beth Boulden WarrenDepartment of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA; Hemophilia and Thrombosis Center, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Adam R WufsusRare Blood Disorders, Medical Affairs Rare Disease, Novo Nordisk Inc, Plainsboro, New Jersey, USA.
Chiara PalliniRare Blood Disorders, Rare Disease Research, Novo Nordisk, Måløv, Denmark.
Michael DockalRare Blood Disorders, Rare Disease Research, Novo Nordisk, Måløv, Denmark.
Marianne KjalkeRare Blood Disorders, Rare Disease Research, Novo Nordisk, Måløv, Denmark.
Keith B NeevesDepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA; Department of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA; Hemophilia and Thrombosis Center, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA. Electronic address: keith.neeves@cuanschutz.edu.

Funding

An integrated computational and experimental approach to understanding the hemostatic response during treatment of bleedingR01HL151984 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FOGELSON, AARON L, LEIDERMAN, KARIN · 2020 to 2023
$2.8M
NHLBI NIH HHS R01 HL151984
6 · The paper itself

Abstract

backgroundInhibition of tissue factor pathway inhibitor (TFPI) is an emerging therapeutic strategy for treatment of hemophilia. Concizumab is a monoclonal antibody that binds TFPI and blocks its inhibition of factor (F)Xa thereby extending the initiation of coagulation and compensating for lack of FVIII or FIX.

objectivesThe objective of this in vitro study was to evaluate how concizumab affects clot formation in hemophilia A under flow.

methodsBlood was collected from normal controls or people with hemophilia A. An anti-FVIII antibody was added to normal controls to simulate hemophilia A with inhibitory antibodies to FVIII. Whole blood and recombinant activated FVII (rFVIIa, 25 nM) or concizumab (200, 1000, and 4000 ng/mL) were perfused at 100 s

resultsConcizumab (1000 and 4000 ng/mL) and rFVIIa both rescued (93%-101%) total platelet accumulation, but only partially rescued (53%-63%) fibrin(ogen) incorporation to normal control levels in simulated hemophilia A. Results using congenital hemophilia A blood confirmed effects of rFVIIa and concizumab. While these 2 agents had similar effect on clot formation under flow, concizumab enhanced thrombin generation in plasma under static conditions to a greater extent than rFVIIa.

conclusionTFPI inhibition by concizumab enhanced activation and aggregation of platelets and fibrin clot formation in hemophilia A to levels comparable with that of rFVIIa.

Indexed as

Antibodies, Monoclonal, HumanizedBlood CoagulationFactor VIIaHemophilia AAntibodies, MonoclonalBlood PlateletsCase-Control StudiesFactor VIIIFibrinHumansLipoproteinsRecombinant ProteinsThrombinAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedconcizumabFactor VIIaFactor VIIIFibrinlipoprotein-associated coagulation inhibitorLipoproteinsrecombinant FVIIaRecombinant ProteinsThrombinblood coagulationhemophilia Ahemorheologylipoprotein-associated coagulation inhibitormicrofluidics

Identifiers

PMID38815755
PMCPMC11343664

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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.