This protocol describes a prospective review to determine the efficacy and safety of anticoagulation for maintaining extracorporeal membrane oxygenation in people of all ages with cardiac or respiratory failure, or both.
Extracorporeal membrane oxygenation (ECMO) is a form of temporary life support used for people with refractory cardiac or respiratory failure, or as a bridge to durable treatment such as transplantation. ECMO circuitry consists of multiple artificial components including large bore cannulae, tubing, connectors, a mechanical pump, and a membrane lung oxygenator that generates a large biomaterial surface area coming into contact with circulating blood (Doyle 2018; Niebler 2019). This serves as a classic model of contact phase activation whereby the artificial surface of essential components activate haemostatic and inflammatory cascades, putting the patient at increased risk of both thrombotic and haemorrhagic complications (Willers 2022). The pump employed may be pulsatile or centrifugal, with differing impacts on cellular and non‐cellular blood components passing through the circuitry. People supported by ECMO are critically ill, which contributes to their haemostatic derangement. Comorbid conditions (e.g. pulmonary embolism, history of bleeding) or devices (e.g. prosthetic heart valves) may perturb the delicate haemostatic balance during ECMO support (Dalton 2015; Sniderman 2020).
From a haematologic perspective, the sequential activation of a broad array of primary and secondary haemostatic pathways yields platelet activation, degranulation, and aggregation, along with the penultimate proteolytic cleavage of soluble fibrinogen into insoluble fibrin monomers that subsequently polymerise to produce a firm platelet plug. Historically, people on ECMO support have needed systemic anticoagulation to mitigate the adverse impact of these complications (Koster 2019; Olson 2021). Despite the development of carefully calibrated anticoagulation strategies that balance the need to mitigate circuit‐related thrombotic deposition against the need to avoid haemorrhage, the risk of both outcomes remains frustratingly high, with an incidence of between 10% and 30% (Thomas 2018). Despite over 50 years of technical and methodologic innovations, there is still no definitive anticoagulation strategy for people on ECMO support.
Types of outcome measures
the authors will explore haemostatic outcomes and patient‐oriented outcomes, using the Core Outcome Set for Research in ECMO as a framework for definitions along with associated measurement tools and time points as applicable (Hodgson 2021).
Primary outcomes
- Thrombotic and thromboembolic events (not including ECMO circuit‐related thrombosis, which requires component or circuit exchange and is a life‐threatening adverse event)
- ECMO circuit‐related thrombosis
- Major bleeding (clinically overt bleeding requiring transfusion of more than 20 mL/kg/24 hours of packed red blood cells (PRBCs) or more than 3 units of PRBCs/24 hours in neonates and paediatric patients or more than 3 units of PRBCs/24 hours in adults)
The definitions for the primary outcomes are per the published Extracorporeal Life Support Organization registry definitions and will be evaluated only during ECMO support (ELSO 2024).
Secondary outcomes
The following five patient‐centred outcomes indicate the efficacy and safety profiles of systemic anticoagulation strategies:
- Allogenic blood product transfusion rate, classified by type and quantified as mL/kg from time of ECMO initiation to time of ECMO separation
- Cerebrovascular events, with subgroup classification for haemorrhagic stroke/intracranial haemorrhage and ischaemic/thromboembolic types, occurring during the index hospital stay (from ECMO initiation to hospital discharge)
- Neurologic recovery, as measured by the Modified Rankin Scale up to 180 days after ECMO initiation
- Health‐related quality of life, as measured by the visual analogue scale of the EuroQol Research Foundation five‐dimension five‐level questionnaire (EQ VAS)
- Mortality up to 60 days from ECMO initiation