Shear Forces Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia.

Humans Animals Mice von Willebrand Factor / metabolism Prospective Studies Mice, Inbred NOD Mice, SCID Blood Platelets / metabolism Thrombocytopenia / therapy
blood platelets extracorporeal membrane oxygenation hemorrhage platelet count thrombocytopenia

Journal

Circulation research
ISSN: 1524-4571
Titre abrégé: Circ Res
Pays: United States
ID NLM: 0047103

Informations de publication

Date de publication:
27 Oct 2023
Historique:
medline: 30 10 2023
pubmed: 26 10 2023
entrez: 26 10 2023
Statut: ppublish

Résumé

Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence and underlying mechanisms remain largely unknown, and a device-related role of ECMO in thrombocytopenia has been hypothesized. This study aims to investigate the mechanisms underlying thrombocytopenia in ECMO patients. In a prospective cohort of 107 ECMO patients, we investigated platelet count, functions, and glycoprotein shedding. In an ex vivo mock circulatory ECMO loop, we assessed platelet responses and VWF (von Willebrand factor)-GP Ibα (glycoprotein Ibα) interactions at low- and high-flow rates, in the presence or absence of red blood cells. The clearance of human platelets subjected or not to ex vivo perfusion was studied using an in vivo transfusion model in NOD/SCID (nonobese diabetic/severe combined Immunodeficient) mice. In ECMO patients, we observed a time-dependent decrease in platelet count starting 1 hour after device onset, with a mean drop of 7%, 35%, and 41% at 1, 24, and 48 hours post-ECMO initiation ( ECMO-associated shear forces induce GP Ibα shedding and thrombocytopenia due to faster clearance of GP Ibα-negative platelets. Inhibiting GP Ibα shedding could represent an approach to reduce thrombocytopenia during ECMO.

Sections du résumé

BACKGROUND BACKGROUND
Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence and underlying mechanisms remain largely unknown, and a device-related role of ECMO in thrombocytopenia has been hypothesized. This study aims to investigate the mechanisms underlying thrombocytopenia in ECMO patients.
METHODS METHODS
In a prospective cohort of 107 ECMO patients, we investigated platelet count, functions, and glycoprotein shedding. In an ex vivo mock circulatory ECMO loop, we assessed platelet responses and VWF (von Willebrand factor)-GP Ibα (glycoprotein Ibα) interactions at low- and high-flow rates, in the presence or absence of red blood cells. The clearance of human platelets subjected or not to ex vivo perfusion was studied using an in vivo transfusion model in NOD/SCID (nonobese diabetic/severe combined Immunodeficient) mice.
RESULTS RESULTS
In ECMO patients, we observed a time-dependent decrease in platelet count starting 1 hour after device onset, with a mean drop of 7%, 35%, and 41% at 1, 24, and 48 hours post-ECMO initiation (
CONCLUSIONS CONCLUSIONS
ECMO-associated shear forces induce GP Ibα shedding and thrombocytopenia due to faster clearance of GP Ibα-negative platelets. Inhibiting GP Ibα shedding could represent an approach to reduce thrombocytopenia during ECMO.

Identifiants

DOI: 10.1161/CIRCRESAHA.123.322752 PMID: 37883587
pubmed: 37883587
doi: 10.1161/CIRCRESAHA.123.322752
doi:

Substances chimiques

von Willebrand Factor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

826-841

Auteurs

Antoine Rauch (A)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Hematology and Transfusion, UFR3S-Université de Lille (A.R., A.D., M.D., E..J., M.D., S.S.).
ORCID: 0000-0002-1182-4131

Annabelle Dupont (A)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Hematology and Transfusion, UFR3S-Université de Lille (A.R., A.D., M.D., E..J., M.D., S.S.).
ORCID: 0000-0002-1554-9931

Mickael Rosa (M)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Hematology and Transfusion, UFR3S-Université de Lille (A.R., A.D., M.D., E..J., M.D., S.S.).
ORCID: 0000-0001-6323-3045

Maximilien Desvages (M)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
ORCID: 0009-0004-1119-1460

Christina Le Tanno (C)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
ORCID: 0009-0006-6112-7277

Johan Abdoul (J)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
ORCID: 0000-0001-5276-5302

Mélusine Didelot (M)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.

Alexandre Ung (A)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
ORCID: 0000-0003-1946-4625

Richard Ruez (R)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.

Emmanuelle Jeanpierre (E)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Hematology and Transfusion, UFR3S-Université de Lille (A.R., A.D., M.D., E..J., M.D., S.S.).

Mélanie Daniel (M)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Hematology and Transfusion, UFR3S-Université de Lille (A.R., A.D., M.D., E..J., M.D., S.S.).
ORCID: 0000-0001-9438-6140

Delphine Corseaux (D)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
ORCID: 0000-0001-8642-1508

Hugues Spillemaeker (H)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Cardiology, UFR3S-Université de Lille (H.S., F.V., E.V.B.).

Julien Labreuche (J)

ULR 2694-METRICS: Évaluation des technologies de santé et des pratiques médicales (J.L.), CHU Lille, University Lille, France.
ORCID: 0000-0002-3384-0423

Bénédicte Pradines (B)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
ORCID: 0000-0003-0371-1580

Natacha Rousse (N)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Cardiac Surgery, UFR3S-Université de Lille (N.R., A.V.).
ORCID: 0000-0003-2837-4285

Peter J Lenting (PJ)

INSERM, UMR-S 1176, Université Paris-Saclay, Le Kremlin Bicêtre, France (P.J.L., C.V.D., C.C.).
ORCID: 0000-0002-7937-3429

Mouhamed D Moussa (MD)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.

André Vincentelli (A)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Cardiac Surgery, UFR3S-Université de Lille (N.R., A.V.).
ORCID: 0000-0003-4081-786X

Jean-Claude Bordet (JC)

Lab Hémostase, HCL-GHE, Lyon, France (J.-C.B.).
ORCID: 0000-0003-1498-703X

Bart Staels (B)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
ORCID: 0000-0002-3784-1503

Flavien Vincent (F)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Cardiology, UFR3S-Université de Lille (H.S., F.V., E.V.B.).
ORCID: 0000-0002-1007-1473

Cécile V Denis (CV)

INSERM, UMR-S 1176, Université Paris-Saclay, Le Kremlin Bicêtre, France (P.J.L., C.V.D., C.C.).
ORCID: 0000-0001-5152-9156

Eric Van Belle (E)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Cardiology, UFR3S-Université de Lille (H.S., F.V., E.V.B.).
ORCID: 0000-0001-6509-443X

Caterina Casari (C)

INSERM, UMR-S 1176, Université Paris-Saclay, Le Kremlin Bicêtre, France (P.J.L., C.V.D., C.C.).
ORCID: 0000-0002-8271-6795

Sophie Susen (S)

Inserm, Institut Pasteur de Lille, France (A.R., A.D., M.R., M. Desvages, C.L.T., J.A., M. Didelot, A.U., R.R., E.J., M. Daniel, D.C., H.S., B.P., N.R., M.D.M., A.V., B.S., F.V., E.V.B., S.S.), CHU Lille, University Lille, France.
Department of Hematology and Transfusion, UFR3S-Université de Lille (A.R., A.D., M.D., E..J., M.D., S.S.).
ORCID: 0000-0001-5953-163X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Eucaryotes › Animaux › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur de von Willebrand › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris SCID › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Sang › Cellules sanguines › Plaquettes › Shear Forces Induced Platelet Clearance Is a...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Anomalies des plaquettes › Thrombopénie › Shear Forces Induced Platelet Clearance Is a...