Coagulation abnormalities in patients with COVID-19 on venovenous ECLS increased risk for technical complications and support times but had no impact on survival

Abstract

Background: Patients with severe coronavirus disease-19 (COVID-19)-associated acute respiratory distress on venovenous extracorporeal lung support (V-V ECLS) showed a high incidence of vascular as well as ECLS-related thrombotic complications. The latter may influence the outcome of the patients.

Methods: This is a retrospective monocentric study on prospectively collected data of technical complications including 69 adult COVID-19 patients on V-V ECLS (ECLS Registry, March 2020 until April 2021) without and with system exchanges. Alterations in ECLS-specific data, hemolysis, coagulation, and hemostasis parameters were analyzed.

Results: Every second COVID-19 patient on V-V ECLS developed technical complications. Optimized ECLS management at our ECLS center reduced cases of acute clot formation (pump head thrombosis, acute oxygenator thrombosis) (17%), and allowed early identification of progressive clotting processes (worsened gas transfer, coagulation disorder) (14%, 54%) with a significant overhang of hyperfibrinolysis (37%). Although COVID-19 disease and technical complications caused the prolonged length of stay at the intensive care unit and ECLS support times, the proportion of successful weaning and survival rates were comparable with patients without system exchange.

Conclusion: The survival of ECLS patients with COVID-19 was independent of the requirement for system exchange due to technical-induced coagulation disorders. Close monitoring for circuit clotting is mandatory in COVID-19 patients and is one prerequisite for successful organ support in these difficult patients.

Keywords: ECMO; SARS-CoV-2; hyperfibrinolysis; outcome; thrombosis.

FIGURE 1

Flow chart of the retrospective observational study of the ECLS registry during 1 year of COVID‐19 pandemic in Regensburg

FIGURE 2

Pump head thrombosis (PHT) (A,B) and acute oxygenator thrombosis (AOT) (C). Time line of respective values (median, IQR) before and after system exchange; “day 0” = system exchange. Patients with system exchange (black dots, PHT, n = 2; AOT, n = 4). (A) Alterations in lactate dehydrogenase (LDH) and (B) plasma‐free hemoglobin (fHb) with PHT and (C) alterations in pressure drop across the oxygenator (dpMO) normalized by blood flow in patients with AOT before and after exchange. White dots in all graphs presented data from patients (n = 20) without a system exchange and a support time ≥12 days. Values at day 9 after ECLS initiation were set as “day 0” and depicted accordingly with no significant temporal changes. Statistics failed due to low sample size of exchanged cases

FIGURE 3

Isolated WGT as a reason for an elective system exchange. Time line of respective values (median, IQR) before and after system exchange; “day 0” = system exchange. Patients with system exchange (black dots, n = 5). (A) Gas flow rate increased before and decreased after exchange. (B) Partial pressure of CO₂ at the outlet of the MO tended to increase (>40 mm Hg) before and decreased after exchange. (C) CO₂ elimination significantly decreased before and improved after exchange. (D) Blood flow decreased after system exchange. (E) The oxygenation capability (PO₂ postMO) remained unchanged, while (F) O₂ transfer decreased before and normalized after exchange. White dots in all graphs presented data from patients (n = 20) without a system exchange and a support time ≥12 days. Values at day 9 after ECLS initiation were set as “day 0” and depicted accordingly with no significant temporal changes. Statistical differences in the time lines of patient groups are shown next to the dots within the graphics (two‐way ANOVA on ranks). *p < 0.05 compared to day 0 (only black dots). a, p < 0.05; b, p < 0.010; c, p < 0.001 compared to the reference group at specified times

FIGURE 4

Clot formation and local fibrinolysis as a reason for an elective system exchange. Time line of respective values (median, IQR) before and after system exchange; “day 0” = system exchange. Patients with system exchange (black dots, n = 6). (A) Fibrinogen and (C) platelet counts remained unchanged. Only (B) d‐dimer levels increased before and decreased after exchange. System exchange had no effect on (D) gas flow rate, (E) partial pressure of CO₂ at the outlet of the MO, (F) CO₂ elimination, (G) blood flow, and (I) O₂ transfer. (H) Partial pressure of O₂ at the outlet of the MO presented significantly lower levels before exchange compared to patients without system exchange. White dots in all graphs presented data from patients of the reference group (n = 20). Statistical differences in the time lines of patient groups are shown next to the dots within the graphics (two‐way ANOVA on ranks). *p < 0.05 compared to day 0 (only black dots). a, p < 0.05; b, p < 0.010; c, p < 0.001 compared to the reference group at specified times

FIGURE 5

Device‐induced hyperfibrinolysis without WGT as a reason for an elective system exchange. Time line of respective values (median, IQR) before and after system exchange; “day 0” = system exchange. Patients with system exchange (black dots, n = 6). (A) Fibrinogen concentrations decreased significantly below 200 mg/L and recovered after exchange. (B) d‐dimer levels significantly increased before and decreased after exchange. (C) Platelet counts decreased before and recovered after exchange. System exchange had no effect on (D) gas flow rate, (E) partial pressure of CO₂ at the outlet of the MO, (F) CO₂ elimination, (G) blood flow, (H) partial pressure of O₂ at the outlet of the MO, and (I) O₂ transfer. White dots presented data from patients of the reference group (n = 20). Statistical differences in the time lines of patient groups are shown next to the dots within the graphics (two‐way ANOVA on ranks). *p < 0.05 compared to day 0 (only black dots). a, p < 0.05; b, p < 0.010 compared to the reference group at specified times

FIGURE 6

Device‐induced hyperfibrinolysis with additional WGT as a reason for an elective system exchange. Time line of respective values (median, IQR) before and after system exchange; “day 0” = system exchange. Patients with system exchange (black dots, n = 7). (A) Fibrinogen concentrations decreased significantly below 200 mg/L and recovered after exchange. (B) d‐dimer levels increased before and decreased after exchange. (C) Platelet counts decreased before and recovered after exchange. COD was accompanied by (D) a significant increase in gas flow rate before and decrease after exchange, (F) a decrease of CO₂ elimination before and improvement after exchange, (H) a decrease in the partial pressure of O₂ at the outlet of the MO before and increase after exchange. (E) partial pressure of CO₂ at the outlet of the MO, (G) blood flow, and (I) O₂ transfer remained unchanged. White dots in all graphs presented data from patients of the reference group (n = 20). Statistical differences in the time lines of patient groups are shown next to the dots (two‐way ANOVA on ranks). *p < 0.05 compared to day 0 (only black dots). a, p < 0.05; b, p < 0.010; c, p < 0.001 compared to the reference group at specified times