Extracorporeal membrane oxygenation aggravates platelet glycoprotein V shedding and δ-granule deficiency in COVID-19–associated acute respiratory distress syndrome

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, a...

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Vydáno v:	Journal of thrombosis and haemostasis Ročník 22; číslo 8; s. 2316 - 2330
Hlavní autoři:	Herrmann, Johannes, Weiss, Lukas J., Just, Bastian, Mott, Kristina, Drayss, Maria, Kleiss, Judith, Riesner, Jonathan, Notz, Quirin, Röder, Daniel, Leyh, Rainer, Beck, Sarah, Weismann, Dirk, Nieswandt, Bernhard, Lotz, Christopher, Meybohm, Patrick, Schulze, Harald
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier Inc 01.08.2024
Témata:	acquired platelet δ-granule deficiency acute respiratory distress syndrome (ARDS) Adult Aged Blood Platelets - metabolism Case-Control Studies COVID-19 - blood COVID-19 - complications COVID-19 - therapy Extracorporeal Membrane Oxygenation extracorporeal membrane oxygenation (ECMO) Female glycoprotein V (GPV), platelets Humans Male Middle Aged Phenotype Platelet Activation Platelet Glycoprotein GPIb-IX Complex Platelet Membrane Glycoproteins - metabolism Respiratory Distress Syndrome - blood Respiratory Distress Syndrome - therapy SARS-CoV-2 acquired platelet δ-granule deficiency glycoprotein V (GPV), platelets extracorporeal membrane oxygenation (ECMO) acute respiratory distress syndrome (ARDS)
ISSN:	1538-7836, 1538-7836
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Shrnutí:	Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation, and thrombus formation by coming in contact with exposed matrix proteins via their surface receptors such as glycoprotein (GP) VI or GPIb/V/IX. Recent research has elucidated a regulatory role of the GPV subunit. The cleaved soluble GPV (sGPV) ectodomain was identified to spatiotemporally control fibrin formation through complex formation with thrombin. We aimed to decipher the impact of ECMO on platelet phenotype and function, including the role of GPV and plasmatic sGPV. We recruited 36 patients with ARDS in the wake of COVID-19 pneumonia and performed a longitudinal comparison of platelet phenotype and function in non-ECMO (n = 23) vs ECMO (n = 13) compared with those of healthy controls. Patients were assessed at up to 3 time points (t1 = days 1-3; t2 = days 4-6; and t3 = days 7-14 after cannulation/study inclusion). Agonist-induced platelet activation was assessed by flow cytometry and revealed decreased GPIIb/IIIa activation and α-granule release in all ARDS patients. During ECMO treatment, agonist-induced δ-granule release continuously decreased, which was independently confirmed by electron microscopy and was associated with a prolonged in vitro bleeding time. GPV expression on the platelet surface markedly decreased in ECMO patients compared with that in non-ECMO patients. Plasma sGPV levels were increased in ECMO patients and were associated with poor outcome. Our data demonstrate an ECMO-intrinsic platelet δ-granule deficiency and hemostatic dysfunction beyond the underlying ARDS.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1538-7836 1538-7836
DOI:	10.1016/j.jtha.2024.05.008