Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study.

To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe coronavirus disease 2019 (COVID-19) and to evaluate their impact on in-hospital mortality. The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models. Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94-4.4]) but not thrombotic events (adjOR = 1.02[0.68-1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4-41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support. In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.

Mansour A ，Flecher E ，Schmidt M ，Rozec B ，Gouin-Thibault I ，Esvan M ，Fougerou C ，Levy B ，Porto A ，Ross JT ，Para M ，Manganiello S ，Lebreton G ，Vincentelli A ，Nesseler N ，ECMOSARS Investigators ... -  《-》

Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis.

This study aimed at analyzing the prevalence, mortality association, and risk factors for bleeding and thrombosis events (BTEs) among adults supported with venovenous extracorporeal membrane oxygenation (VV-ECMO). We queried the Extracorporeal Life Support Organization registry for adults supported with VV-ECMO from 2010 to 2017. Multivariable logistic regression modeling was used to assess the association between BTEs and in-hospital mortality and the predictors of BTEs. Among 7579 VV-ECMO patients meeting criteria, 40.2% experienced ≥ 1 BTE. Thrombotic events comprised 54.9% of all BTEs and were predominantly ECMO circuit thrombosis. BTE rates decreased significantly over the study period (p < 0.001). The inpatient mortality rate was 34.9%. Bleeding events (1.69 [1.49-1.93]) were more strongly associated with in-hospital mortality than thrombotic events (1.23 [1.08-1.41]) p < 0.01 for both. The BTEs most strongly associated with mortality were ischemic stroke (4.50 [2.55-7.97]) and medical bleeding, including intracranial (5.71 [4.02-8.09]), pulmonary (2.02 [1.54-2.67]), and gastrointestinal (1.54 [1.2-1.98]) hemorrhage, all p < 0.01. Risk factors for bleeding included acute kidney injury and pre-ECMO vasopressor support and for thrombosis were higher weight, multisite cannulation, pre-ECMO arrest, and higher PaCO2 at ECMO initiation. Longer time on ECMO, younger age, higher pH, and earlier year of support were associated with bleeding and thrombosis. Although decreasing over time, BTEs remain common during VV-ECMO and have a strong, cumulative association with in-hospital mortality. Thrombotic events are more frequent, but bleeding carries a higher risk of inpatient mortality. Differential risk factors for bleeding and thrombotic complications exist, raising the possibility of a tailored approach to VV-ECMO management.

Nunez JI ，Gosling AF ，O'Gara B ，Kennedy KF ，Rycus P ，Abrams D ，Brodie D ，Shaefi S ，Garan AR ，Grandin EW ... -  《-》

Anticoagulation Management in Severe Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation.

To explore special coagulation characteristics and anticoagulation management in extracorporeal membrane oxygenation (ECMO)-assisted patients with coronavirus disease 2019 (COVID-19). Single-center, retrospective observation of a series of patients. Laboratory-confirmed severe COVID-19 patients who received venovenous ECMO support from January 20-May 20, 2020. This study analyzed the anticoagulation management and monitoring strategies, bleeding complications, and thrombotic events during ECMO support. Eight of 667 confirmed COVID-19 patients received venovenous ECMO and had an elevated D-dimer level before and during ECMO support. An ECMO circuit pack (oxygenator and tubing) was replaced a total of 13 times in all 8 patients, and coagulation-related complications included oxygenator thrombosis (7/8), tracheal hemorrhage (5/8), oronasal hemorrhage (3/8), thoracic hemorrhage (3/8), bleeding at puncture sites (4/8), and cannulation site hemorrhage (2/8). Hypercoagulability and secondary hyperfibrinolysis during ECMO support in COVID-19 patients are common and possibly increase the propensity for thrombotic events and failure of the oxygenator. Currently, there is not enough evidence to support a more aggressive anticoagulation strategy.

Guo Z ，Sun L ，Li B ，Tian R ，Zhang X ，Zhang Z ，Clifford SP ，Liu Y ，Huang J ，Li X ... -  《-》

Observational study of thrombosis and bleeding in COVID-19 VV ECMO patients.

Ripoll B ，Rubino A ，Besser M ，Patvardhan C ，Thomas W ，Sheares K ，Shanahan H ，Agrawal B ，Webb S ，Vuylsteke A ... -  《-》

Venovenous Extracorporeal Membrane Oxygenation With Prophylactic Subcutaneous Anticoagulation Only: An Observational Study in More Than 60 Patients.

Extracorporeal lung support and therapeutic anticoagulation are dogmatically linked for most clinicians in fear of clotting of the extracorporeal circuit. In the last decade, however, we have learned that bleeding complications in the course of extracorporeal membrane oxygenation (ECMO) therapy are common and not occasionally limiting or fatal. Even though international guidelines lowered the PTT-target values, ECMO therapy without anticoagulation has only been reported sporadically in case reports heretofore. This monocentric, observational study was designed to evaluate a protocol for venovenous ECMO therapy without additional anticoagulation. Patients without former thrombotic events solely received thrombosis prophylaxis with 40 mg subcutaneous enoxaparin per day like every critical care patient. After approval by the local ethics committee (Albert-Ludwigs-University Freiburg ethics committee, EK 513/14) all consecutive patients treated with venovenous ECMO therapy since introduction of the protocol have been identified. Digital charts of the patients have been evaluated with special regard to bleeding and thrombotic or embolic events or breakdown of the extracorporeal circuit. Sixty-one patients received venovenous ECMO therapy with prophylactic subcutaneous enoxaparin only. Median duration of ECMO therapy was 7 days (2-32). Overall 560 ECMO days have been observed. No system exchange because of thrombotic occlusion was necessary within the permitted 5 days run time of the centrifugal pump. Overall we identified thrombotic complications in four patients. In three of them centrifugal pump after a runtime of more than 5 days unexpectedly stopped completely because of thrombotic occlusion. In all cases pump exchange was performed promptly and patients did not incur hypoxic deficit. One other patient received substitution of blood products and coagulation factor concentrates because of severe bleeding and sustained myocardial infarction the day after. Only 18% of patients presented with essential clinical bleeding after 7 days of therapy. No fatal bleeding event and no intracranial hemorrhage was observed. Patients required only a third of blood product transfusion compared to published data. Venovenous ECMO therapy with prophylactic anticoagulation only was feasible in this study. It was not associated with an increased rate of system exchanges compared to regimes with therapeutic anticoagulation in registry data. It provides the potential to relevantly decrease the incidence of severe bleeding events and blood transfusion requirements. The apodictic adherence to anticoagulation in therapeutic dosage should be critically scrutinized in every patient.

Krueger K ，Schmutz A ，Zieger B ，Kalbhenn J ... -  《-》