Evidence map›Paper›PMID 34611669›Full record

ArticlemedRxiv : the preprint server for health sciences2021

Anti-PF4 VITT antibodies are oligoclonal and variably inhibited by heparin.

B Singh, A Kanack, A Bayas, G George, M Y Abou-Ismail, M Kohlhagen, M Christ, M Naumann, K Moser, K Smock and 3 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2021. 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, 13 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

B SinghDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
A KanackDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
A BayasDepartment of Neurology and Clinical Neurophysiology, University Hospital of Augsburg, Augsburg, Germany.
G GeorgeDepartment of Medicine, University of Colorado, Aurora, CO, USA.
M Y Abou-IsmailDepartment of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
M KohlhagenDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
M ChristDepartment of Neurology and Clinical Neurophysiology, University Hospital of Augsburg, Augsburg, Germany.
M NaumannDepartment of Neurology and Clinical Neurophysiology, University Hospital of Augsburg, Augsburg, Germany.
K MoserDepartment of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
K SmockDepartment of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
A GrazioliDepartment of Medicine, National Institutes of Health, Bethesda, MD, USA and University of Maryland School of Medicine, Baltimore, MD, USA.
D MurrayDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
A PadmanabhanDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic in Arizona · USUniversity Hospital Augsburg · DEUniversity of Utah · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Maryland, Baltimore · US

Funding

New Approaches to Pathogenesis and Diagnosis of Heparin-Induced Thrombocytopenia (HIT)K08HL133479 · NHLBI · VERSITI WISCONSIN, INC. · PI PADMANABHAN, ANAND · 2017 to 2021
$836k
NHLBI NIH HHS K08 HL133479
6 · The paper itself

Abstract

backgroundCOVID-19 vaccines have been associated with a rare thrombotic and thrombocytopenic reaction, Vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by platelet-activating anti-PF4 antibodies. This study sought to assess clonality of VITT antibodies and evaluate their characteristics in antigen-based and functional platelet studies.

methodsAnti-PF4 antibodies were isolated from five patients with VITT secondary to ChAdOx1 nCoV-19 (n=1) or Ad26.COV2.S (n=4) vaccination. For comparative studies with heparin-induced thrombocytopenia (HIT), anti-PF4 antibodies were isolated from one patient with spontaneous HIT, another with "classical" HIT, and two patients with non-pathogenic (non-platelet activating) anti-PF4 antibodies. Isolated antibodies were subject to ELISA and functional testing, and mass spectrometric evaluation for clonality determination.

resultsAll five VITT patients had oligoclonal anti-PF4 antibodies (3 monoclonal, one bi- and one tri-clonal antibodies), while HIT anti-PF4 antibodies were polyclonal. Notably, like VITT antibodies, anti-PF4 antibodies from a spontaneous HIT patient were monoclonal. The techniques employed did not detect non-pathogenic anti-PF4 antibodies. The ChAdOx1 nCoV-19-associated VITT patient made an excellent recovery with heparin treatment. In vitro studies demonstrated strong inhibition of VITT antibody-induced platelet activation with therapeutic concentrations of heparin in this and one Ad26.COV2.S-associated VITT patient. Oligoclonal VITT antibodies with persistent platelet-activating potential were detected at 6 and 10 weeks after acute presentation in two patients tested. Two of the 5 VITT patients had recurrence of thrombocytopenia and one patient had focal seizures several weeks after acute presentation.

conclusionOligoclonal anti-PF4 antibodies mediate VITT. Heparin use in VITT needs to be further studied.

Identifiers

PMID34611669
PMCPMC8491860
OpenAlexW3202837716

What OpenQuestion holds

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LicenceCC BY-ND
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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.