Evidence map›Paper›PMID 33914406›Full record

ArticleJournal of thrombosis and haemostasis : JTH2021

FVIII inhibitors display FV-neutralizing activity in the prothrombin time assay.

Andrea Arsiccio, James Beavis, Sanj Raut, Carmen H Coxon

Open access · hybridAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 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
0.3field-weighted citation impact, top 45% of its field
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, 2 citations in OpenAlex.

  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

4 authors at 3 institutions in 2 countries.

Andrea ArsiccioDepartment of Applied Science and Technology, Politecnico di Torino, Torino, Italy.
James BeavisOxford Haemophilia Centre, Churchill Hospital, Oxford, UK.
Sanj RautNational Institute for Biological Standards and Control, Potters Bar, UK.
Carmen H CoxonNational Institute for Biological Standards and Control, Potters Bar, UK.ORCID 0000-0001-8694-4894
National Institute for Biological Standards and Control · GBChurchill Hospital · GBPolitecnico di Torino · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe coagulation factors (F)V and VIII are homologous proteins that support hemostasis through their regulation of FX activity. Hemophilia A (HA) patients have reduced FVIII activity and a prolonged bleeding time that is corrected through the administration of exogenous FVIII. Around one-third of severe HA patients develop FVIII neutralizing antibodies, known as "inhibitors," which neutralize FVIII activity and preclude them from further FVIII therapy.

objectivesWe hypothesized that, based on the degree of homology between FV and FVIII (~40%), FVIII-neutralizing antibodies could cross react with FV. To test this hypothesis, a panel of recombinant, patient-derived, FVIII-neutralizing antibodies were screened for cross-reactivity against FV.

methodsFactor V and FVIII activity was measured using one-stage clotting assays; structural analysis was carried out using a structural approach.

resultsWe detected FV neutralizing activity with the anti-FVIII A2 domain antibody NB11B2. Because this antibody was derived from an HA inhibitor patient, FV-neutralizing activity was then evaluated in a number of HA inhibitor patient plasma samples; nine alloimmune samples had FV-neutralizing activity whereas no FV neutralizing activity was found in the two autoimmune samples available. We next examined the degree of surface homology between FV and FVIII and found that structural similarity could explain the cross reactivity of the anti-A2 antibody and likely accounts for the cross reactivity we observed in patient samples.

conclusionsAlthough this novel observation is of interest, further work will be needed to determine whether FV neutralization in HA patient samples contributes to their bleeding diathesis.

Indexed as

Factor VIIIHemophilia ABlood Coagulation TestsHemostasisHumansProthrombin TimeFactor VIIIcoagulationcoagulation factor Vcoagulation factor VIIIFVIII inhibitorshemostasis

Identifiers

PMID33914406
PMCPMC8360109
OpenAlexW3159794961

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.