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Article Dans Une Revue Circulation Research Année : 2023

Shear Force-Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia

Antoine Rauch
Annabelle Dupont
Mickael Rosa
Maximilien Desvages
Christina Le Tanno
Johan Abdoul
Mélusine Didelot
  • Fonction : Auteur
Alexandre Ung
Richard Ruez
  • Fonction : Auteur
Emmanuelle Jeanpierre
  • Fonction : Auteur
Mélanie Daniel
Delphine Corseaux
Hugues Spillemaeker
  • Fonction : Auteur
Julien Labreuche
Bénédicte Pradines
Natacha Rousse
Peter Lenting
Mouhamed Moussa
  • Fonction : Auteur
André Vincentelli
Jean-Claude Bordet
Bart Staels
Flavien Vincent
Cécile Denis
Eric van Belle
Caterina Casari
Sophie Susen

Résumé

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 aimed to investigate the mechanisms underlying thrombocytopenia in ECMO patients. 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: 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 ( P =0.00013, P <0.0001, and P <0.0001, respectively), regardless of the type of ECMO. This drop in platelet count was associated with a decrease in platelet GP Ibα expression (before: 47.8±9.1 versus 24 hours post-ECMO: 42.3±8.9 mean fluorescence intensity; P =0.002) and an increase in soluble GP Ibα plasma levels (before: 5.6±3.3 versus 24 hours post-ECMO: 10.8±4.1 µg/mL; P <0.0001). GP Ibα shedding was also observed ex vivo and was unaffected by (1) red blood cells, (2) the coagulation potential, (3) an antibody blocking VWF–GP Ibα interaction, (4) an antibody limiting VWF degradation, and (5) supraphysiological VWF plasma concentrations. In contrast, GP Ibα shedding was dependent on rheological conditions, with a 2.8-fold increase at high- versus low-flow rates. Platelets perfused at high-flow rates before being transfused to immunodeficient mice were eliminated faster in vivo with an accelerated clearance of GP Ibα–negative versus GP Ibα–positive platelets. 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.

Dates et versions

hal-04455871 , version 1 (13-02-2024)

Identifiants

Citer

Antoine Rauch, Annabelle Dupont, Mickael Rosa, Maximilien Desvages, Christina Le Tanno, et al.. Shear Force-Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia. Circulation Research, 2023, 133 (10), pp.826-841. ⟨10.1161/CIRCRESAHA.123.322752⟩. ⟨hal-04455871⟩

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