Current Understanding of How Extracorporeal Membrane Oxygenators Activate Haemostasis and Other Blood Components

Abstract

Extracorporeal membrane oxygenators are used in critical care for the management of severe respiratory and cardiac failure. Activation of the coagulation system is initiated by the exposure of blood to synthetic surfaces and the shear stresses of the circuit, especially from device pumps. Initial fibrinogen deposition and subsequent activation of coagulation factors and complement allow platelets and leucocytes to adhere to oxygenator surfaces and enhance thrombin generation. These changes and others contribute to higher rates of thrombosis seen in these patients. In addition, bleeding rates are also high. Primary haemostasis is impaired by platelet dysfunction and loss of their key adhesive molecules and shear stress causes an acquired von Willebrand defect. In addition, there is also altered fibrinolysis and lastly, administration of systemic anticoagulation is required to maintain circuit patency. Further research is required to fulyl establish the complexities of the haemostatic changes with these devices, and to elucidate the mechanistic changes that are mainly responsible so that plans can be made to reduce their complications and improve management.

Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO

“…In the absence of preexisting coagulopathy, hemostatic dysfunction during ECMO occurs as a consequence of sheer stress and exposure of blood to the non-biologic surfaces of the ECMO circuit [15,16]. Mechanical forces provoke activation of platelets and coagulation factors, fibrinogen deposition, adherence to device surfaces, and thrombin generation.…”

Platelet Count and Function during Pediatric Extracorporeal Membrane Oxygenation

“…22 Activation of the complement system leads to further activation of platelets and PMNs and increased adhesion and release of cytokines, which contribute to the overall hypercoagulable state. [22][23][24][25] Some reports suggest distinct periods of activation in neonates, with contact activation and complement activation predominant in the first 24 hours after ECMO exposure followed by a second period of activation characterized by clotting and fibrinolytic activity without activation of the complement system observed 72 hours after ECMO initiation. 26 The cell-based model of coagulation proposes that subendothelial tissue factor exposure and binding and activation of circulating Factor VII then cause downstream thrombin generation.…”

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation

“…77 However, the etiology of hypofibrinogenemia can be multifactorial, such as dilutional effect due to large extracorporeal volume requiring saline or red cell prime, underlying conditions such as sepsis and liver failure, increased consumption due to thrombosis, disseminated intravascular coagulation (DIC), and hyperfibrinolysis. 78,79 Whole blood testing with viscoelastic hemostatic assays (ROTEM or TEG) can be used in identifying severe hyperfibrinolysis. 80 The mechanism of fibrinolysis in ECMO patients is not very clear and probably involves multiple mechanisms, one being secondary fibrinolysis, in which the production of thrombin stimulates release of tPA from endothelial cells.…”