Evidence map›Paper›PMID 41623545›Full record

ArticleEJHaem2026

Combined Antithrombin and Heparin Supplementation to Blood for Restoring Heparin Responsiveness After Andexanet Alfa Exposure: An In Vitro Model.

Amir L Butt, Hisako Okada, Kofi B Vandyck, Nana Toyoda, Shinobu Itagaki, Kenneth E Stewart, Kenichi A Tanaka

Abstract read
In one paragraph

Article in EJHaem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

7 authors.

Amir L ButtDepartment of Anesthesiology University of Oklahoma Health Oklahoma City Oklahoma USA.ORCID https://orcid.org/0000-0002-4802-4162
Hisako OkadaDepartment of Anesthesiology University of Oklahoma Health Oklahoma City Oklahoma USA.
Kofi B VandyckDepartment of Anesthesiology University of Oklahoma Health Oklahoma City Oklahoma USA.
Nana ToyodaDepartment of Surgery University of Oklahoma Health Oklahoma City Oklahoma USA.
Shinobu ItagakiDepartment of Surgery University of Oklahoma Health Oklahoma City Oklahoma USA.
Kenneth E StewartDepartment of Anesthesiology University of Oklahoma Health Oklahoma City Oklahoma USA.ORCID https://orcid.org/0000-0001-9768-0417
Kenichi A TanakaDepartment of Anesthesiology University of Oklahoma Health Oklahoma City Oklahoma USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Andexanet alfa, a Gla-domainless mutant factor Xa (GDXa), reverses oral FXa inhibitors but can cause severe heparin resistance during cardiopulmonary bypass (CPB). Antithrombin (AT) supplementation may mitigate this effect, though dosing evidence is limited. Methods: We evaluated in vitro the effectiveness of combined heparin and AT in restoring heparin responsiveness after andexanet exposure. Whole blood and platelet-poor plasma from surgical patients on CPB were spiked with andexanet at target concentrations of 2.9 and 4 µM, respectively. Heparin responsiveness was assessed using kaolin-activated clotting time (ACT), ellagic acid-activated thromboelastometry (INTEM), and thrombin generation (TG) assays. Heparin alone or with AT (0.8-3.1 µM in whole blood; 1.1-4.4 µM in plasma) simulated clinical AT dosing (25-100 U/kg). Results: Andexanet shortened ACT by 68% versus native on-CPB blood. Heparin alone or low-dose AT failed to restore ACT, while high-dose AT with heparin prolonged ACT to > 400 s. INTEM showed a 102% increase in clotting time with moderate-dose AT, with modest Conclusion: High-dose AT with heparin mitigates andexanet-induced heparin resistance in vitro, though residual TG and clot formation suggest ongoing thrombotic risk, warranting further study. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Indexed as

activated clotting timeandexanet alfaantithrombincardiopulmonary bypassheparin resistance

Identifiers

PMID41623545
PMCPMC12857465

What OpenQuestion holds

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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.