The Role of Excessive Anticoagulation and Missing Hyperinflammation in ECMO-Associated Bleeding

Abstract

Extracorporeal membrane oxygenation (ECMO) is increasingly used in carefully selected patients with cardiac or respiratory failure. However, complications are common and can be associated with worse outcomes, while data on risk factors and outcomes are inconsistent and sparse. Therefore, we sought to investigate potential risk factors and predictors of haemorrhage and adverse events during ECMO and its influence on mortality. We retrospectively reviewed all patients on ECMO support admitted to intensive care units of a tertiary university centre in Austria. In a period of ten years, ECMO support was used in 613 patients, with 321 patients meeting the inclusion criteria of this study. Haemorrhage, occurring in more than one third of the included patients (123, 38%), represented the most common and serious ECMO complication, being associated with an increased one year mortality (51% vs. 35%, p = 0.005). The main risk factors for haemorrhage were severity of the disease (hazard ratio (HR) = 1.01, p = 0.047), a prolonged activated partial thromboplastin time (HR = 1.01, p = 0.007), and lower values of C-reactive protein (HR = 0.96, p = 0.005) and procalcitonin (HR = 0.99, p = 0.029). In summary, haemorrhage remained the main ECMO complication with increased mortality. Moreover, we reported a possible association of lower inflammation and bleeding during ECMO support for the first time. This generated a new hypothesis that warrants further research. Finally, we recommend stricter monitoring of anticoagulation especially in patients without hyperinflammation.

Extracorporeal membrane oxygenation for cardiogenic shock: a meta-analysis of mortality and complications

“…Comparable to literature, hemorrhage was the second most frequent complication in nearly half of the patients, which is in line with the largest meta-analysis so far, reporting any kind of hemorrhage in 40% [ 15 ]. Going into greater detail confirmed the cannulation and surgical area being the most common sites of bleeding [ 32 – 34 ]. However, the latter findings may be weakened by the fact that only one study reported on the use of the ELSO bleeding definition [ 23 ], despite the definition´s existence of more than 8 years.…”

ECMO in Cardiogenic Shock: Time Course of Blood Biomarkers and Associated Mortality

“…The association of hyperinflammation with the occurrence of thrombosis, and a potentially reduced risk of bleeding, has already been described in literature [ 33 , 34 ]. Moreover, the methods of systemic inflammatory response syndrome after cardiopulmonary bypass minimization are being applied in daily clinical practice [ 35 ].…”

“…In the case of cardiopulmonary bypass recommendations, including the application and further development of circuit bonding and leukodepletion, use of glucocorticoids, aprotinin, complement inhibitors, etc., exist [ 35 ]. However, in the case of va-ECMO, there is a paucity of evidence on the role of inflammation, originating mostly from retrospective or animal studies [ 26 , 33 , 36 , 37 ]. Further studies are warranted to clarify the role of inflammation in the outcome of ECMO patients and determine potential therapeutic interventions.…”

Anticoagulation Strategies during Extracorporeal Membrane Oxygenation: A Narrative Review

“…Hyperinflammation may lead to a limitation of the UFH effect by decreasing antithrombin levels or increasing heparin binding to acute phase proteins [ 42 , 43 , 44 ]. A recent report on a possible association between bleeding and unintended excessive anticoagulation in ECMO patients without hyperinflammation remains to be confirmed in larger cohorts [ 13 ]. Finally, despite the extensive development of anticoagulants, ECMO pumps, oxygenators, and tubing systems, the systemic inflammatory response syndrome and distorted hemostasis remain a clinical concern.…”

“…The initiation of ECMO support is associated with complex inflammatory and coagulation responses, as a reaction to the blood encountering the large artificial surface of an extracorporeal system circuit [ 12 ]. These processes may further lead to endothelial injury and disrupted microcirculation with consequent end-organ dysfunction and the need for systemic anticoagulation [ 12 , 13 ].…”