Evidence map›Paper›PMID 27188532›Full record

ArticleXenotransplantation2016

Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor.

L Burdorf, A Riner, E Rybak, I I Salles, S F De Meyer, A Shah, K J Quinn, D Harris, T Zhang, D Parsell and 14 more

Erratum issuedAbstract read
In one paragraph

Article in Xenotransplantation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  2. Review
  3. Article
  4. Pig heart and lung xenotransplantation: Present status.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022
    Article
  5. Article
  6. Article
  7. Article
  8. Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022
    Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Xenotransplantation: past, present, and future.Current opinion in organ transplantation · 2017
    Review
  17. Lung xenotransplantation.Current opinion in organ transplantation · 2017
    Review
  18. Article
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 3 institutions in 3 countries.

L Burdorf *Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
A Riner *Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
E RybakDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
I I SallesLaboratory for Thrombosis Research, IRF-Ls, Kulak KU Leuven, Belgium.
S F De MeyerLaboratory for Thrombosis Research, IRF-Ls, Kulak KU Leuven, Belgium.
A ShahDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
K J QuinnDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
D HarrisDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
T ZhangDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
D ParsellDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
F AliDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
E SchwartzDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
E KangDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
X ChengDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
E SievertDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
Y ZhaoDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
G BraileanuDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
C J PhelpsRevivicor, Inc., Blacksburg, VA, United States.
D L AyaresRevivicor, Inc., Blacksburg, VA, United States.
H DeckmynLaboratory for Thrombosis Research, IRF-Ls, Kulak KU Leuven, Belgium.
R N Pierson *Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
A M Azimzadeh *Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, and VA Maryland Health Care System, Baltimore, MD, United States.
Amy Dandro
Kasinath Karavi
University of Maryland, Baltimore · USKU Leuven · BENIHR Imperial Biomedical Research Centre · GB

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2010 to 2024
$26.3M
British Heart Foundation FS/10/004/28165British Heart Foundation PG/14/90/31219NIAID NIH HHS U19 AI090959
6 · The paper itself

Abstract

backgroundHere, we ask whether platelet GPIb and GPIIb/IIIa receptors modulate platelet sequestration and activation during GalTKO.hCD46 pig lung xenograft perfusion.

methodsGalTKO.hCD46 transgenic pig lungs were perfused with heparinized fresh human blood. Results from perfusions in which αGPIb Fab (6B4, 10 mg/l blood, n = 6), αGPIIb/IIIa Fab (ReoPro, 3.5 mg/l blood, n = 6), or both drugs (n = 4) were administered to the perfusate were compared to two additional groups in which the donor pig received 1-desamino-8-d-arginine vasopressin (DDAVP), 3 μg/kg (to pre-deplete von Willebrand Factor (pVWF), the main GPIb ligand), with or without αGPIb (n = 6 each).

resultsPlatelet sequestration was significantly delayed in αGPIb, αGPIb+DDAVP, and αGPIb+αGPIIb/IIIa groups. Median lung "survival" was significantly longer (>240 vs. 162 min reference, p = 0.016), and platelet activation (as CD62P and βTG) were significantly inhibited, when pigs were pre-treated with DDAVP, with or without αGPIb Fab treatment. Pulmonary vascular resistance rise was not significantly attenuated in any group, and was associated with residual thromboxane and histamine elaboration.

conclusionsThe GPIb-VWF and GPIIb/IIIa axes play important roles in platelet sequestration and coagulation cascade activation during GalTKO.hCD46 lung xenograft injury. GPIb blockade significantly reduces platelet activation and delays platelet sequestration in this xenolung rejection model, an effect amplified by adding αGPIIb/IIIa blockade or depletion of VWF from pig lung.

Indexed as

AnimalsAnimals, Genetically ModifiedBlood PlateletsGraft SurvivalHeterograftsHumansLungLung TransplantationPlatelet ActivationPlatelet AggregationPlatelet Glycoprotein GPIb-IX ComplexPlatelet Glycoprotein GPIIb-IIIa ComplexSwineThrombocytopeniaTransplantation, Heterologousvon Willebrand FactorPlatelet Glycoprotein GPIb-IX ComplexPlatelet Glycoprotein GPIIb-IIIa Complexvon Willebrand Factorcoagulationex-vivo perfusionFabGalTKO.hCD46GlycoproteinGPIbGPIIb/IIIalungplatelet activationXenotransplantation

Identifiers

PMID27188532
PMCPMC5052084
OpenAlexW2397300230

What OpenQuestion holds

Textmetadata
LicenceTDM
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.