Anticoagulation Strategies during Extracorporeal Membrane Oxygenation: A Narrative Review

Abstract

The development of extracorporeal life support technology has added a new dimension to the care of critically ill patients who fail conventional treatment options. Extracorporeal membrane oxygenation (ECMO)-specialized temporary life support for patients with severe cardiac or pulmonary failure-plays a role in bridging the time for organ recovery, transplant, or permanent assistance. The overall patient outcome is dependent on the underlying disease, comorbidities, patient reaction to critical illness, and potential adverse events during ECMO. Moreover, the contact of the blood with the large artificial surface of an extracorporeal system circuit triggers complex inflammatory and coagulation responses. These processes may further lead to endothelial injury and disrupted microcirculation with consequent end-organ dysfunction and the development of adverse events like thromboembolism. Therefore, systemic anticoagulation is considered crucial to alleviate the risk of thrombosis and failure of ECMO circuit components. The gold standard and most used anticoagulant during extracorporeal life support is unfractionated heparin, with all its benefits and disadvantages. However, therapeutic anticoagulation of a critically ill patient carries the risk of clinically relevant bleeding with the potential for permanent injury or death. Similarly, thrombotic events may occur. Therefore, different anticoagulation strategies are employed, while the monitoring and the balance of procoagulant and anticoagulatory factors is of immense importance. This narrative review summarizes the most recent considerations on anticoagulation during ECMO support, with a special focus on anticoagulation monitoring and future directions.

Keywords: ECMO; adverse events; anticoagulation; complications; extracorporeal life support; future directions; inflammation; monitoring; mortality.

Figure 1

Schematic presentation of a diffusion membrane showing blood flow between the gas and water-filled network of hollow fibers. With permission of Maquet.

Figure 2

Presentation of prothrombotic and prohemorrhagic factors with an influence on homeostasis. Achieving a balance between the risk of bleeding and thrombosis is both critical and complex in patients receiving ECMO support. Aside from the initiation and propagation of the inflammatory response (proinflammatory state) and the activation of the coagulation cascade (prothrombotic state), ECMO may also lead to platelet dysfunction, fibrinolysis, malfunction of von Willebrand factor, and consumption of coagulation factors leading to a prohemorrhagic state.

Figure 3

The heparin–antithrombin–thrombin (HAT) complex inactivates the coagulation factors, leading to the blockade of the fibrinogen conversion to fibrin. The red arrows starting from the HAT complexes show the place of its action on factors XIIa, XIa, IXa, Xa, and IIa. At the bottom of the figure, the fibrinogen molecule (blue) is shown with two thrombin molecules (red) catalyzing its transition to the active form, fibrin. (Adapted with permission from Dreamstime.com. 2022, Illustration 183970741 ©Juan Gaertner and Illustration 233379397 ©Volodymyr Dvornyk, accessed on 10 August 2022).