Evidence map›Paper›PMID 38724509›Full record

ArticleNature communications2024

Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding.

Wojciech Jankowski, Stepan S Surov, Nancy E Hernandez, Atul Rawal, Marcos Battistel, Daron Freedberg, Mikhail V Ovanesov, Zuben E Sauna

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. 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

8 authors.

Wojciech Jankowski *Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-7000-9057
Stepan S Surov *Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA.ORCID http://orcid.org/0009-0003-5796-2155
Nancy E HernandezHemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-8307-4704
Atul RawalHemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0003-3443-693X
Marcos BattistelLaboratory of Bacterial Polysaccharides, Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA.
Daron FreedbergLaboratory of Bacterial Polysaccharides, Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0003-1991-5174
Mikhail V OvanesovHemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA.
Zuben E SaunaHemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation & Research, US FDA, Silver Spring, MD, USA. Zuben.Sauna@fda.hhs.gov.ORCID http://orcid.org/0000-0001-8202-5188

Funding

U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration) None
6 · The paper itself

Abstract

Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC binding affinity, retain FXa-enzymatic activity and reduce the DOAC-associated bleeding by restoring hemostasis in mice treated with apixaban. Importantly, the FXaDOACs reversal agents we designed, unlike andexanet alfa, do not inhibit TFPI, and consequently, may have a safer thrombogenic profile.

Indexed as

Factor Xa InhibitorsHemorrhageHemostasisPyrazolesPyridonesAnimalsAnticoagulantsFactor XaHumansMaleMiceRecombinant ProteinsAnticoagulantsapixabanFactor XaFactor Xa InhibitorsPRT064445PyrazolesPyridonesRecombinant Proteins

Identifiers

PMID38724509
PMCPMC11082157

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.