Evidence map›Paper›PMID 31989085›Full record

ArticleResearch and practice in thrombosis and haemostasis2020

Microfluidic hemophilia models using blood from healthy donors.

Xinren Yu, Karen A Panckeri, Lacramioara Ivanciu, Rodney M Camire, Carmen H Coxon, Adam Cuker, Scott L Diamond

Open access · goldAbstract read
In one paragraph

Article in Research and practice in thrombosis and haemostasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
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  3. Microfluidic hemophilia models using blood from healthy donors.Research and practice in thrombosis and haemostasis · 2020
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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 at 4 institutions in 2 countries.

Xinren YuDepartment of Chemical and Biomolecular Engineering Institute for Medicine and Engineering University of Pennsylvania Philadelphia Pennsylvania.
Karen A PanckeriPenn Comprehensive Hemophilia and Thrombosis Program Hospital of the University of Pennsylvania Philadelphia Pennsylvania.
Lacramioara IvanciuThe Raymond G. Perelman Center for Cellular and Molecular Therapeutics The Children's Hospital of Philadelphia Philadelphia Pennsylvania.
Rodney M CamireThe Raymond G. Perelman Center for Cellular and Molecular Therapeutics The Children's Hospital of Philadelphia Philadelphia Pennsylvania.
Carmen H CoxonNational Institute for Biological Standards and Control Potters Bar UK.
Adam CukerPenn Comprehensive Hemophilia and Thrombosis Program Hospital of the University of Pennsylvania Philadelphia Pennsylvania.
Scott L DiamondDepartment of Chemical and Biomolecular Engineering Institute for Medicine and Engineering University of Pennsylvania Philadelphia Pennsylvania.
University of Pennsylvania · USHospital of the University of Pennsylvania · USChildren's Hospital of Philadelphia · USNational Institute for Biological Standards and Control · GB

Funding

Blood Systems BiologyR01HL103419 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DIAMOND, SCOTT L · 2010 to 2019
$7.4M
Multiscale Analysis of TraumaU01HL131053 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DIAMOND, SCOTT L · 2016 to 2020
$3.8M
Blood Systems BiologyR33HL087317 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DIAMOND, SCOTT L · 2006 to 2008
$937k
NHLBI NIH HHS R01 HL103419NHLBI NIH HHS R33 HL087317NHLBI NIH HHS U01 HL131053
6 · The paper itself

Abstract

backgroundMicrofluidic clotting assays permit drug action studies for hemophilia therapeutics under flow. However, limited availability of patient samples and Inter-donor variability limit the application of such assays, especially with many patients on prophylaxis.

objectiveTo develop approaches to phenocopy hemophilia using modified healthy blood in microfluidic assays.

methodsCorn trypsin inhibitor (4 µg/mL)-treated healthy blood was dosed with either anti-factor VIII (FVIII; hemophilia A model) or a recombinant factor IX (FIX) missense variant (FIX-V181T; hemophilia B model). Treated blood was perfused at 100 s

resultsAnti-FVIII partially blocked fibrin production on collagen/TF, but completely blocked fibrin production on collagen/FXIa, a phenotype reversed with 1 µmol/L bispecific antibody (emicizumab), which binds FIXa and factor X. As expected, emicizumab had no significant effect on healthy blood (no anti-FVIII present) perfused over collagen/FXIa. The efficacy of emicizumab in anti-FVIII-treated healthy blood phenocopied the action of emicizumab in the blood of a patient with hemophilia A perfused over collagen/FXIa. Interestingly, a patient-derived FVIII-neutralizing antibody reduced fibrin production when added to healthy blood perfused over collagen/FXIa. For low TF surfaces, reFIX-V181T (50 µg/mL) fully blocked platelet and fibrin deposition, a phenotype fully reversed with anti-TFPI.

conclusionTwo new microfluidic hemophilia A and B models demonstrate the potency of anti-TF pathway inhibitor, emicizumab, and a patient-derived inhibitory antibody. Using collagen/FXIa-coated surfaces resulted in reliable and highly sensitive hemophilia models.

Indexed as

drug evaluationfibrinhemophiliahemostasismicrofluidics

Identifiers

PMID31989085
PMCPMC6971334
OpenAlexW2994464664

What OpenQuestion holds

Textmetadata
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.