RESUMO
BACKGROUND: 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. OBJECTIVES: We aimed to decipher the impact of ECMO on platelet phenotype and function, including the role of GPV and plasmatic sGPV. METHODS: 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). RESULTS: 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. CONCLUSION: Our data demonstrate an ECMO-intrinsic platelet δ-granule deficiency and hemostatic dysfunction beyond the underlying ARDS.
RESUMO
Interhospital transport of acute respiratory distress syndrome (ARDS) patients bears transport-associated risks. It is unknown how interhospital extracorporeal membrane oxygenation (ECMO) transfer of COVID-19 patients by mobile ECMO units affects ARDS mortality. We compared the outcome of 94 COVID-19 patients cannulated in primary care hospitals and retrieved by mobile ECMO-teams to that of 84 patients cannulated at five German ECMO centers. Patients were recruited from March 2020 to November 2021. Twenty-six transports were airborne, 68 were land-based. Age, sex, body-mass-index, Simplified Acute Physiology Score (SAPS) II, days invasively ventilated, and P/F-Ratio before ECMO initiation were similar in both groups. Counting only regional transports (≤250 km), mean transport distance was 139.5 km ± 17.7 km for helicopter (duration 52.5 ± 10.6 minutes) and 69.8 km ± 44.1 km for ambulance or mobile intensive care unit (duration 57.6 ± 29.4 minutes). Overall time of vvECMO support (20.4 ± 15.2 ECMO days for transported patients vs. 21.0 ± 20.5 for control, p = 0.83) and days invasively ventilated (27.9 ± 18.1 days vs. 32.6 ± 25.1 days, p = 0.16) were similar. Overall mortality did not differ between transported patients and controls (57/94 [61%] vs. 51/83 [61%], p = 0.43). COVID-19 patients cannulated and retrieved by mobile ECMO-teams have no excess risk compared with patients receiving vvECMO at experienced ECMO centers. Patients with COVID-19-associated ARDS, limited comorbidities, and no contraindication for ECMO should be referred early to local ECMO centers.
