Evidence map›Paper›PMID 38919958›Full record

ArticleHemaSphere2024

Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease.

Myrthe J van Dijk, Titine J J Ruiter, Sigrid van der Veen, Minke A E Rab, Brigitte A van Oirschot, Jennifer Bos, Cleo Derichs, Anita W Rijneveld, Marjon H Cnossen, Erfan Nur and 7 more

Abstract read
In one paragraph

Article in HemaSphere, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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

5 citing papers in PubMed.

  1. Article
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  4. Review
  5. 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

17 authors.

Myrthe J van DijkCenter for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Titine J J RuiterCentral Diagnostic Laboratory and Research University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.ORCID 0009-0008-3656-7718
Sigrid van der VeenCenter for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Minke A E RabCentral Diagnostic Laboratory and Research University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Brigitte A van OirschotCentral Diagnostic Laboratory and Research University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Jennifer BosCentral Diagnostic Laboratory and Research University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Cleo DerichsCenter for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Anita W RijneveldDepartment of Hematology, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.
Marjon H CnossenDepartment of Pediatric Hematology, Erasmus MC Sophia Children's Hospital University Medical Center Rotterdam Rotterdam The Netherlands.
Erfan NurDepartment of Hematology Amsterdam University Medical Center, University of Amsterdam Amsterdam The Netherlands.
Bart J BiemondDepartment of Hematology Amsterdam University Medical Center, University of Amsterdam Amsterdam The Netherlands.
Marije BartelsCenter for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Roger E G SchutgensCenter for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.ORCID 0000-0002-2762-6033
Wouter W van SolingeCentral Diagnostic Laboratory and Research University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Judith J M JansSection Metabolic Diagnostics, Department of Genetics University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.
Eduard J van BeersCenter for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.ORCID https://orcid.org/0000-0002-3934-7189
Richard van WijkCentral Diagnostic Laboratory and Research University Medical Center Utrecht, Utrecht University Utrecht The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3-DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator-initiated, open-label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019-003438-18), untargeted metabolomics was used to explore the overall metabolic effects of 8-week treatment with mitapivat in the dose-finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate-adjusted

Identifiers

PMID38919958
PMCPMC11196954

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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.