Elsevier

Thrombosis Research

Volume 173, January 2019, Pages 172-177
Thrombosis Research

Full Length Article
Anticoagulation during ECMO in neonatal and paediatric patients

https://doi.org/10.1016/j.thromres.2018.05.009Get rights and content

Highlights

  • A review of the pathophysiology, anticoagulation management in paediatric and neonatal ECMO.

  • The choice of anticoagulation, monitoring and therapeutic targets varies worldwide.

  • Further research is required into the haemostatic changes during paediatric ECMO.

Abstract

Extracorporeal Membrane Oxygenation (ECMO) is a form of Extracorporeal Life Support (ECLS) which is used frequently in the paediatric and neonatal setting to support either the pulmonary, or both the pulmonary and cardiac systems. Management of ECMO requires the use of systemic anticoagulation to prevent patient and circuit based thrombosis, which in turn increases the risk of haemorrhage. A number of coagulation tests, laboratory and point of care based, are used to monitor anticoagulation, however the evidence for correlation of the test results with level of anticoagulant and clinical outcomes in children remains poor.

Introduction

Extracorporeal Membrane Oxygenation (ECMO) is a form of Extracorporeal Life Support (ECLS) which supports either the pulmonary system or both the pulmonary and cardiac systems, with the use of an artificial circuit. ECMO provides cardiac and respiratory support whilst reversible pathophysiological processes are allowed time to resolve, spontaneously or through medical or surgical interventions. As such ECMO is not considered a therapeutic intervention, rather a supportive therapy, and should be reserved for those with reversible pathophysiological processes [1].

ECMO involves removal of deoxygenated venous blood from the patient, passing the blood through a membrane oxygenator which includes pressurisation, and then returning the now oxygenated blood to either the venous or arterial side of the circulation. The site of blood collection and return in neonates and children is dependent upon the type of ECMO required and many patient factors. ECMO was first used successfully in a neonate with meconium aspiration and pulmonary hypertension in 1975. [2]. The development and growth of ECMO in neonates appeared to be faster than that in the adult population, which is in contrast to the majority of medical developments and technological interventions [3]. Over the following few decades the number of centres performing ECMO continued to grow, and ECMO within the neonatal and paediatric population became common practice. As the expertise and experience with ECMO increased so too did the survival rates [4]. However, across the different ECMO centres there is significant variation in the circuits used, both in terms of structure and design, oxygenators, pumps as well as the administration and monitoring of anticoagulation. There is no standard language or definitions for reporting of these variables in data and published records, which makes comparison of published literature very difficult.

Section snippets

Paediatric & neonatal indications for ECMO

Paediatric and neonatal patients who require ECMO are a heterogeneous group and the underlying pathophysiology of these indications may result in a coagulopathy of varying degrees and aetiologies. Neonates have the best survival rates compared with other ages and disease states [4,5], as listed in Table 1. The indications for ECMO are largely divided into respiratory and cardiac conditions, with the latter being further divided into those who have had cardiac surgery and those who have not.

Pathophysiology of ECMO

ECMO changes the blood-endothelial interface to blood-biomaterial, with continuous contact of circulating blood to the plastic tubing, resulting in activation of both the inflammatory and coagulation systems. This activation shifts the balance of normal haemostasis to a pro-coagulant state, as well as a pro-inflammatory state, of which the mechanisms and complexity is poorly understood [9].

Shortly after the commencement of ECMO the artificial surface of the circuit becomes coated with blood

Complications of ECMO

Haemorrhage and thrombosis, remain the most common causes of morbidity and mortality in patients who receive ECMO therapy, despite significant improvements and experience in management. Haemorrhagic complications of ECMO are likely multifactorial, and may be due to both patient and circuit related factors. Thrombosis is defined as the formation of a blood clot, within either a blood vessel, circuit or filter that obstructs the flow of blood. The three aspects of Virchow's triad;

Anticoagulation in paediatric & neonatal ECMO

There is a paucity of data and research relating to the pharmacokinetic and pharmacodynamic profile of anticoagulation, as well as inadequate validation of anticoagulation management in children in general [[26], [27], [28]]. The majority of recommendations for the use of anticoagulation in paediatrics comes from prospective paediatric cohort & observational studies, extrapolation from adult research, as well as historical and anecdotal experience within individual centres [29]. In addition to

Antithrombin (AT)

Antithrombin (AT) is a serine protease and naturally occurring anticoagulant, which inhibits thrombin (Factor IIa), Factor Xa and other serine proteases which are involved in the coagulation pathway. AT levels in neonates and paediatric patients are physiologically lower, and do not reach adult levels until 3–6 months of age. [36,44]. As AT is required for UFH to function as an anticoagulant, there is a concern that replacement of AT would increase bleeding risks in paediatric patients on ECMO [

Haemostatic adjuncts

Haemostatic adjuncts, such as Prothrombin Complex Concentrates (PCCs), recombinant activated Factor VII (rVIIa), and antifibrinolytic agent's ε-aminocaproic acid and tranexamic acid, are agents which are used clinically to stop haemorrhage. Although bleeding secondary to anticoagulation on ECMO is common, they are not routinely used in paediatric ECMO patients. The reasons for this are multifactorial, with a lack of dosing strategies and research in paediatric patients, as well as an increased

Monitoring of anticoagulation

Close monitoring of UFH whilst patients are on ECMO is critical, due to underlying patient factors of coagulopathy, haemodilution and recent or open surgical wounds, as well as the relatively narrow therapeutic window of UFH. The optimal method for monitoring of anti-coagulation in paediatric and neonatal patients on ECMO is unknown, with each institution following individual guidelines, with a focus on local experience with assays, laboratory support and clinician interpretation. Having said

Conclusion

Extracorporeal Membrane Oxygenation (ECMO) is a form of ECLS which provides cardiac and respiratory support for patients with reversible pathophysiological processes. ECMO is most commonly used in neonatal and paediatric patients, and due to both underlying patient factors, as well as introduction of the ECMO circuit, there is activation of both a pro-coagulant and pro-inflammatory state. As a result patients require systemic anticoagulation with UFH to reduce their risk of both circuit and

Conflict of interest

None of the authors have any conflicts of interest to declare.

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