Current practice optimization suggestions and future perspectives on transfusion in patients supported by extracorporeal membrane oxygenation: a narrative review

Introduction

Background

Extracorporeal membrane oxygenation (ECMO) support has become the mainstay of cardiopulmonary replacement therapy in critically ill patients with terminal heart and/or lung disease (1). Its indications are becoming increasingly broader due to increased awareness and technological advances (2). Currently, ECMO support is undertaken for patients of varying age (from newborns to adults) and with different underlying conditions.

The ECMO population requires more transfusions than other critically ill patients, and almost all ECMO patients are exposed to at least one blood product unit during support. The reasons for prompting practitioners to transfuse are multifactorial. ECMO leads to an increased risk of bleeding due to therapeutic cannulation, hemodilution, and activation of coagulation factors and cells. Priming volume leads to the hemodilution of almost all blood components, including coagulation factors and platelets. The extent of hemodilution depends on the patient’s body surface area and the desired flow rate. Contact and shear stress between the blood column and the non-endothelial surface of the circuit leads to hemolysis and an inflammatory response. These can induce endothelial dysfunction and activation of the coagulation cascade and, potentially, consumptive coagulopathy. The absorption capacity of the artificial surface can contribute to the depletion of fibrinogen and other coagulation factors (3). Furthermore, as with all extracorporeal support, ECMO requires anticoagulants to avoid thrombosis of the patient’s vessels, and clotting of the circuit.

During ECMO support, the negative pressure and turbulence generated by the pumps can lead to hemolysis, and hence anemia. Red blood cell (RBC) disruption releases factors that promote von Willebrand factor mediated-platelet adhesion and thrombosis (4). The cell-free plasma hemoglobin scavenges endothelial nitric oxide, limiting its bioavailability, leading to microvascular vasomotor dysregulation. Along with bleeding and hemolysis, anemia of chronic disease can contribute to reduced hemoglobin levels in patients on ECMO support. Therefore, practitioners are inclined to transfuse these patients to restore oxygen-carrying capacity and maintain adequate oxygen delivery (DO2).

Rationale and knowledge gap

Blood transfusions have a questionable cost-benefit ratio since they are expensive, and can increase morbidity and mortality. Packed red blood cells (PRBCs) are a risk-bearing therapy, particularly in high-acuity patients, such as those on ECMO. This special population has several intensive care unit (ICU)-related risk factors, including volume depletion or overload, infections, longer duration of mechanical ventilation, and longer length of ICU stay. All of these can contribute to development of such transfusion-related complications as acute lung injury, infections, fluid overload, and immunoreactions (5-7) that can precipitate the clinical conditions of these patients. Furthermore, prolonged storage of PRBCs can worsen hemolysis, and result in the release of free hemoglobin (fHb), which in turn causes the depletion of nitrogen oxides, and endothelial microvascular vasoconstriction (8).

To our knowledge, few prior studies have examined strategies to spare PRBC, such optimizing blood flow and fluid balance or dynamically changing ECMO configurations. However, advances in technology consistently impacted on transfusion requirements in patients on ECMO support. The most recent recommendations from the Extracorporeal Life Support Organization (ELSO) suggest maintaining hematocrit levels above 40% (which translates to hemoglobin levels above 13 g/dL) (9) to optimize oxygen delivery with the lowest reasonable blood circuit flow. Increasing expertise and bioengineering advances over the last 10 years have called these recommendations into question. In fact, modern ECMO circuits reduce the risk of bleeding and hemolysis (3,10). In addition, despite the severity of illness seen in the ECMO population, an increasing number of observational studies have shown the non-inferiority, in terms of morbidity and mortality, of a restrictive approach to transfusion practice with respect to liberal ones (11), as demonstrated in non-ECMO supported critically ill patients (12-15). In a recent systematic review and meta-analysis, the median transfusion threshold for both venovenous (VV) and venoarterial (VA) ECMO was 8 g/dL (12). In a recent Cochrane review, this transfusion threshold was shown not to increase mortality risk compared with higher thresholds (13).

Objective

This review examines the practice of blood transfusion in studies of ECMO patients and whether a hemoglobin trigger is considered when physicians decide to transfuse. In addition, we aimed to identify alternative blood transfusion strategies to maintain adequate oxygenation, such as optimal fluid balance, anticoagulation protocols, and dynamic ECMO configurations. We present this article in accordance with the Narrative Review reporting checklist (available at https://aob.amegroups.org/article/view/10.21037/aob-23-11/rc).

Methods

The methods of our search are summarized in Table 1.

Discussion

Transfusion practice in VV ECMO

Refractory respiratory failure during conventional therapy is the main indication for VV ECMO support. Oxygen uptake is the major issue in these patients, who generally maintain oxygen consumption in the normal range. In this setting, transfusing the patient does not further improve oxygen delivery despite an adequate oxygen uptake through an oxygenator, unless hemoglobin levels reach a critical point (14,15). Increasing oxygen extraction can allow oxygen uptake to remain stable until oxygen delivery falls below a critical level, as during severe anemia or hemorrhagic shock (16). There is still insufficient proof that increasing hemoglobin levels leads to increased oxygen delivery in the presence of oxygen extraction within normal range. When oxygen extraction is near 50%, it cannot increase in the presence of progressive anemia, and oxygen consumption tends to decrease simultaneously. A retrospective study investigated the relationship between transfusion practice and changes in perfusion markers, such as mixed venous saturation (SvO₂) and cerebral tissue oxygenation measured by near infrared spectroscopy (NIRS) (17). Most transfusions did not result in statistically significant changes in perfusion markers, revealing that they were administered when patients were in a non-dependent oxygen delivery state. It is possible that different practitioners transfuse patients in order to exploit the hemoglobin buffer effect in counteracting the oxygen diffusion deficit. However, futile RBC transfusion can limit the patient’s oxygen delivery by different mechanisms: (I) an increase in hemoglobin oxygen affinity by depletion of 2–3 diphosphoglycerate (2–3 DPG) and adenosine-triphosphate (ATP) induced by long storage of RBCs (18); (II) an increase in blood viscosity and vascular resistance, leading to a potential decrease in cardiac output; (III) an increase in hemolysis and thrombosis events. In fact, PRBCs have increased osmolar fragility, and are prone to hemolysis (19), and free plasma hemoglobin can increase vascular resistance by depletion of endothelial NO (20).

The TRAIN-ECMO survey investigated transfusion practices among different centers in patients on VV ECMO compared with other critically ill patients, with a special emphasis on hemoglobin thresholds used to guide the transfusion therapy. The survey revealed a high variability in the Hb trigger in these centers, as shown in Table 2. Furthermore, patients on VV ECMO support are transfused at a higher Hb threshold compared with other critically ill patients, but this gap was narrower in higher volume centers (28). This high variability and the liberality in transfusion practice in VV ECMO patients is perhaps due to the lack of evidence on optimal transfusion triggers for hemoglobin values in this population (29). As a result, various observational studies (Table 2) have confirmed that patients receiving VV ECMO are highly transfused, with a prevalence approaching 100% (26,30-35), even in non-bleeding patients (36). However, a multicenter, prospective, cohort study reported a reduced PRBC transfusion percentage, likely due to advances in technologies and increased understanding of patient blood management (37).

Anticoagulation protocols can increase the risk of bleeding, and the need for blood products. In a monocentric prospective study, an anticoagulation protocol with only subcutaneous enoxaparin in prophylactic dosage, was found to obviate the need for blood products while achieving an adequate safely profile in 61 patients receiving VV ECMO and without a history of thrombosis (38). This finding should prompt clinicians to reconsider the ELSO recommendations to use therapeutic dosages of heparin in every patient on VV ECMO.

Several studies support the safety and feasibility of a restrictive transfusion strategy in VV ECMO patients. In a retrospective study, a hemoglobin trigger of 7 g/dL did not increase mortality in 18 patients undergoing VV ECMO for severe acute respiratory distress syndrome (ARDS) (25). Similarly, another retrospective study found that a gradual decrease in the hemoglobin threshold from 10 to 7 g/dL led to a reduced volume of blood transfused, without a significant clinical impact in patients on VV ECMO for severe ARDS (39). In a recent meta-analysis, a higher transfusion threshold was shown to be associated with increased mortality (12). For this reason and the above-mentioned transfusion-related complications, the decision to transfuse patients should be weighed considering not only absolute hemoglobin values, but the entire clinical picture (e.g., hemodynamic parameters, circuit change, bleeding). PRBC transfusions should be given when anemia becomes critical and affects the body’s oxygen delivery (DO2) and coagulation status. In fact, if the patient’s metabolic needs can be met with alternative treatments, such as adjusting Qec and optimizing fluid balance, the decision to transfuse may not be favorable for patient outcomes. In the PROTECMO study, an increased daily fluid balance led to increased mortality in ARDS patients supported with VV ECMO (37). Indeed, a more positive fluid balance exposes the patient to the risk of a non-beneficial high blood flow rate, with an increased risk of hemolysis and further PRBC transfusions. Furthermore, the authors concluded that PRBC transfusion increases survival only when given for hemoglobin level below 7 g/dL. In light of this, the administration of fluids is critical, and the decision of which fluids to administer is fundamental since the principal limiting factor is the time that these fluids remain in the intravascular system.

Transfusion practice during VA ECMO

Transfusion is more common in VA ECMO than in VV ECMO (8) because of the different pathophysiological setting. VA ECMO can unload the right ventricle and provide adequate oxygen to the end organs and system. It is likely that there is also an increased risk of bleeding due to arterial cannulations and more anticoagulation requirements to avoid thrombosis in the heart and in low-flow territories (5,13,40,41). In fact, patients who require VA ECMO typically have a hemostatic imbalance at the time of cannulation, and starting extracorporeal support is only an additional indication for anticoagulation therapy (42). Moreover, thrombocytopenia is frequent due to underlying illness, and the extracorporeal circuit can worsen this condition, leading to activation of inflammatory pathways and hemolysis (43). Indeed, platelets can adhere to surface fibrinogen, leading to thrombocytopenia. There is now a novel ECMO circuit that features reduced platelet adhesion and minor pro-inflammatory properties (44). Finally, a difference should be considered for central and peripheral cannulation since peripheral cannulation requires mandatory care of the SvO₂ because the venous blood that enters a damaged lung can carry prevalently poorly oxygenated blood flow to the brain.

In the setting of moderate to severe hemorrhage, it is probably safer to withhold anticoagulation for VV ECMO than it is for VA ECMO, even if several studies have reported no life-threatening thromboembolic complications after withholding anticoagulation therapy for days (41,45). In VA ECMO patients, even exposure to systemic anticoagulation only at the time of weaning resulted in a reduced risk of bleeding and blood transfusion requirements without a significant increase in thromboembolic events.

There is heterogeneity among centers regarding hemoglobin trigger used to transfuse patients on VA ECMO. As shown in Table 3, some centers adopt a restrictive approach while others remain anchored to a liberal approach to transfusion. As regard the trigger for transfusion, some centers adopt hemoglobin values, others hematocrit, and others do not specify the trigger used to guide transfusion. The survival to discharge and PRBC requirements remain variable.

Practices to reduce RBC transfusion during ECMO support

Several strategies can be employed by healthcare practitioners to decrease the requirement for RBC transfusion during ECMO support. Initially, minimizing blood loss through the reduction or limitation of blood samplings can be beneficial. Secondly, decreasing the duration of ECMO support may contribute to this goal (62). Lastly, standardizing transfusion practices via local protocols can provide a consistent approach to minimizing transfusion necessities (63,64).

Transfusion practice aims to increase oxygen delivery, yet there are different strategies to reach this objective without transfusing patients.

Blood flow rate

The blood flow rate during ECMO is usually set at 2–4 L/min, depending on the patient’s size, cardiac function, and oxygenation needs. A higher blood flow rate can help improve oxygenation and remove carbon dioxide, but it also increases the risk of bleeding and other complications. Monitoring and maintaining fluid balance is a crucial aspect of the management of patients on ECMO support. In fact, hypovolemia leads to a reduced blood flow rate and hypoperfusion. On the other hand, fluid overload can also reduce the blood flow rate, increasing systemic blood pressure. Furthermore, the hemodilution induced by a positive fluid balance leads to a higher and inefficient blood flow rate because it will not be associated with higher oxygen delivery.

Autotransfusion during decannulation

One investigation (65) revealed a significant reduction in the volume of RBCs transfused due to autotransfusion during decannulation. The authors identified additional advantages of autologous blood transfusion, such as a diminished immune response, a decreased risk of infectious complications, a shorter duration of ICU stay, and an improvement in pulmonary function. In another study (63), autotransfusion is a practice incorporated within the patient blood management protocol.

Perfusion markers

As stated above, practitioners are more likely to transfuse ECMO patients, in order to decrease the risk of cardiac ischemia and to counteract bleeding and hemodilution induced by circuit priming. Despite several studies suggesting that a restrictive transfusion strategy can be safe and effective, other authors have raised concerns about applying such an approach in ECMO population, highlighting the importance of carefully assessing each patient’s individual risk factors and clinical situation when deciding on the appropriate transfusion strategy. In reality, the predefined threshold-based approach may be inappropriate in the setting of VA-ECMO due to differences in DO2 requirements between patients based on their etiology, disease severity, and ECMO modality. In addition, large variations in DO2 can be observed in the same patient and between ECMO settings. From this perspective, practitioners should transfuse patients not to reach an established Hb value but to match metabolic demands. Therefore, a more individualized strategy guided by a DO2 surrogate, central venous oxygen saturation (ScvO₂), may be more appropriate in this population. The ScvO₂ approach has recently been shown to be associated with reduced PRBCs in two randomized controlled trials in cardiac surgery patients (66,67). Furthermore, looking at the trend in ScvO₂ might provide useful information on changes in oxygen extraction during transfusion and could ameliorate patient blood management in ECMO population.

Pulsating ECMO

Recently, there has been increasing interest in pulsatile ECMO as an alternative to continuous VA ECMO. Pulsatile flow should ameliorate end-organ perfusion, especially for brain, kidney and coronary circulation (68). Furthermore, it is believed that pulsatile flow can help to maintain microcirculation and reduce inflammation and thrombosis (69). Moreover, pulsatile flow may be crucial in unloading the left ventricle in refractory cardiogenic shock. If confirmed by future research, pulsatile VA ECMO may guarantee more efficient oxygen delivery and left ventricle unloading compared to classic non-pulsatile VA ECMO, and therefore might lead to a decrease in the need for transfusion.

Hybrid configurations

Several subsets of patients on ECMO support can experience a change in their condition and physiologic demand. For this reason, ECMO configurations have evolved from “pure” veno-venous or veno-arterial ECMO to more complex hybrid configurations, with the use of additional cannulas to dynamically match physiological needs over time (70). For example, patients supported with VV ECMO can have inadequate drainage or perfusion, cardiovascular failure (frequently of the right heart), and drops in oxygen delivery despite adequate oxygen uptake. The addition of a third cannula in these patients can be critical in restoring the perfusion deficit and the unloading of the right or both ventricles. In patients on VV ECMO, cardiac unloading can be achieved with additional mechanical support devices, such as an intra-aortic balloon pump, counterpulsation or short-term assist devices (71). Similarly, patients on VA ECMO can develop a differential oxygenation as cardiac native function begins to recover. In this condition, the upper body can be less oxygenated (Harlequin syndrome or North/South syndrome), and an extra inflow cannula introduced into the internal jugular vein (veno-venoarterial extracorporeal membrane oxygenation or V-VA ECMO) can provide oxygenated blood to the left ventricle, and thus the coronary and aortic arch vessels. In general, inserting an additional cannula for hybrid ECMO carries further risk of bleeding in patients with therapeutic anticoagulation. Balancing risks and benefits when considering whether to initiate an advanced ECMO configuration is critical in avoiding wasted efforts to spare blood transfusions. ECMO with two oxygenators in parallel can improve oxygen uptake. This is particularly indicated when patients are developing multi-organ failure despite conventional ECMO configurations. The use of a double oxygenator system provides a backup in case of a malfunction or failure of one oxygenator, increasing the reliability of the ECMO system. More interesting is the use of two oxygenators in parallel, which may decrease resistance to blood flow leading to a reduction in blood trauma and shear stress.

Conclusions

PRBC transfusion has a questionable cost-benefit ratio. The most widespread clinical practice considers only the hemoglobin values when deciding a patient’s transfusion needs. However, a growing body of literature suggests combining the hemoglobin value with physiological parameters, such as oxygen extraction to obviate the need for PRBC and improve patient blood management. As an increase in oxygen extraction can counteract the decrease in oxygen carrying capacity only in cases of isovolemic anemia, it is crucial to optimize fluid balance and dynamically adjust ECMO blood flow. Moreover, advances in medical technologies and clinical expertise will likely make ECMO circuits increasingly efficient in matching a patient’s metabolic demand and reducing PRBC transfusion requirements.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Blood for the series “Blood Transfusion Practice in ECMO Patients”. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aob.amegroups.org/article/view/10.21037/aob-23-11/rc

Peer Review File: Available at https://aob.amegroups.org/article/view/10.21037/aob-23-11/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aob.amegroups.org/article/view/10.21037/aob-23-11/coif). The series “Blood Transfusion Practice in ECMO Patients” was commissioned by the editorial office without any funding or sponsorship. G.M. served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Marasco SF, Lukas G, McDonald M, et al. Review of ECMO (extra corporeal membrane oxygenation) support in critically ill adult patients. Heart Lung Circ 2008;17:S41-7. [Crossref] [PubMed]
2. Kelly B, Carton E. Extended Indications for Extracorporeal Membrane Oxygenation in the Operating Room. J Intensive Care Med 2020;35:24-33. [Crossref] [PubMed]
3. Doyle AJ, Hunt BJ. Current Understanding of How Extracorporeal Membrane Oxygenators Activate Haemostasis and Other Blood Components. Front Med (Lausanne) 2018;5:352. [Crossref] [PubMed]
4. Valladolid C, Yee A, Cruz MA. von Willebrand Factor, Free Hemoglobin and Thrombosis in ECMO. Front Med (Lausanne) 2018;5:228. [Crossref] [PubMed]
5. Bosboom JJ, Klanderman RB, Zijp M, et al. Incidence, risk factors, and outcome of transfusion-associated circulatory overload in a mixed intensive care unit population: a nested case-control study. Transfusion 2018;58:498-506. [Crossref] [PubMed]
6. Philip J, Pawar A, Chatterjee T, et al. Non Infectious Complications Related to Blood Transfusion: An 11 year Retrospective Analysis in a Tertiary Care Hospital. Indian J Hematol Blood Transfus 2016;32:292-8. [Crossref] [PubMed]
7. Vlaar AP, Juffermans NP. Transfusion-related acute lung injury: a clinical review. Lancet 2013;382:984-94. [Crossref] [PubMed]
8. Lehle K, Philipp A, Zeman F, et al. Technical-Induced Hemolysis in Patients with Respiratory Failure Supported with Veno-Venous ECMO - Prevalence and Risk Factors. PLoS One 2015;10:e0143527. [Crossref] [PubMed]
9. Extracorporeal Life Support Organization (ELSO). General Guidelines for all ECLS Cases. August, 2017. Accessed on 10 January 2023.
10. Martucci G, Panarello G, Occhipinti G, et al. Impact of cannula design on packed red blood cell transfusions: technical advancement to improve outcomes in extracorporeal membrane oxygenation. J Thorac Dis 2018;10:5813-21. [Crossref] [PubMed]
11. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409-17. [Crossref] [PubMed]
12. Abbasciano RG, Yusuff H, Vlaar APJ, et al. Blood Transfusion Threshold in Patients Receiving Extracorporeal Membrane Oxygenation Support for Cardiac and Respiratory Failure-A Systematic Review and Meta-Analysis. J Cardiothorac Vasc Anesth 2021;35:1192-202. [Crossref] [PubMed]
13. Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev 2021;12:CD002042. [PubMed]
14. Holst LB. Benefits and harms of red blood cell transfusions in patients with septic shock in the intensive care unit. Dan Med J 2016;63:B5209. [PubMed]
15. Roberson RS, Bennett-Guerrero E. Impact of red blood cell transfusion on global and regional measures of oxygenation. Mt Sinai J Med 2012;79:66-74. [Crossref] [PubMed]
16. Kim HS, Park S. Blood Transfusion Strategies in Patients Undergoing Extracorporeal Membrane Oxygenation. Korean J Crit Care Med 2017;32:22-8. [Crossref] [PubMed]
17. Fiser RT, Irby K, Ward RM, et al. RBC transfusion in pediatric patients supported with extracorporeal membrane oxygenation: is there an impact on tissue oxygenation? Pediatr Crit Care Med 2014;15:806-13. [Crossref] [PubMed]
18. Valtis DJ. Defective gas-transport function of stored red blood-cells. Lancet 1954;266:119-24. [Crossref] [PubMed]
19. Blasi B, D'Alessandro A, Ramundo N, et al. Red blood cell storage and cell morphology. Transfus Med 2012;22:90-6. [Crossref] [PubMed]
20. Reiter CD, Wang X, Tanus-Santos JE, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 2002;8:1383-9. [Crossref] [PubMed]
21. Guirand DM, Okoye OT, Schmidt BS, et al. Venovenous extracorporeal life support improves survival in adult trauma patients with acute hypoxemic respiratory failure: a multicenter retrospective cohort study. J Trauma Acute Care Surg 2014;76:1275-81. [Crossref] [PubMed]
22. Lewandowski K, Rossaint R, Pappert D, et al. High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation. Intensive Care Med 1997;23:819-35. [Crossref] [PubMed]
23. Panigada M, L'Acqua C, Passamonti SM, et al. Comparison between clinical indicators of transmembrane oxygenator thrombosis and multidetector computed tomographic analysis. J Crit Care 2015;30:441.e7-13. [Crossref] [PubMed]
24. Trudzinski FC, Minko P, Rapp D, et al. Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis. Ann Intensive Care 2016;6:66. [Crossref] [PubMed]
25. Voelker MT, Busch T, Bercker S, et al. Restrictive transfusion practice during extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome. Artif Organs 2015;39:374-8. [Crossref] [PubMed]
26. Martucci G, Panarello G, Occhipinti G, et al. Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality. J Intensive Care Med 2019;34:630-9. [Crossref] [PubMed]
27. Smith C, Bellomo R, Raman JS, et al. An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population. Ann Thorac Surg 2001;71:1421-7. [Crossref] [PubMed]
28. Martucci G, Grasselli G, Tanaka K, et al. Hemoglobin trigger and approach to red blood cell transfusions during veno-venous extracorporeal membrane oxygenation: the international TRAIN-ECMO survey. Perfusion 2019;34:39-48. [Crossref] [PubMed]
29. Vlaar AP, Oczkowski S, de Bruin S, et al. Transfusion strategies in non-bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. Intensive Care Med 2020;46:673-96. [Crossref] [PubMed]
30. Aubron C, Cheng AC, Pilcher D, et al. Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study. Crit Care 2013;17:R73. [Crossref] [PubMed]
31. Guimbretière G, Anselmi A, Roisne A, et al. Prognostic impact of blood product transfusion in VA and VV ECMO. Perfusion 2019;34:246-53. [Crossref] [PubMed]
32. Mazzeffi M, Greenwood J, Tanaka K, et al. Bleeding, Transfusion, and Mortality on Extracorporeal Life Support: ECLS Working Group on Thrombosis and Hemostasis. Ann Thorac Surg 2016;101:682-9. [Crossref] [PubMed]
33. Panholzer B, Meckelburg K, Huenges K, et al. Extracorporeal membrane oxygenation for acute respiratory distress syndrome in adults: an analysis of differences between survivors and non-survivors. Perfusion 2017;32:495-500. [Crossref] [PubMed]
34. Tauber H, Streif W, Fritz J, et al. Predicting Transfusion Requirements During Extracorporeal Membrane Oxygenation. J Cardiothorac Vasc Anesth 2016;30:692-701. [Crossref] [PubMed]
35. Weingart C, Lubnow M, Philipp A, et al. Comparison of Coagulation Parameters, Anticoagulation, and Need for Transfusion in Patients on Interventional Lung Assist or Veno-Venous Extracorporeal Membrane Oxygenation. Artif Organs 2015;39:765-73. [Crossref] [PubMed]
36. Raasveld SJ, Karami M, van den Bergh WM, et al. RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study. Crit Care Med 2022;50:224-34. [Crossref] [PubMed]
37. Martucci G, Schmidt M, Agerstrand C, et al. Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study. Lancet Respir Med 2023;11:245-55. [Crossref] [PubMed]
38. Krueger K, Schmutz A, Zieger B, et al. Venovenous Extracorporeal Membrane Oxygenation With Prophylactic Subcutaneous Anticoagulation Only: An Observational Study in More Than 60 Patients. Artif Organs 2017;41:186-92. [Crossref] [PubMed]
39. Pulsipher AM, Pratt EH, Brucker A, et al. Hemoglobin Transfusion Thresholds in Patients on VV-ECMO for ARDS. Am J Respir Crit Care Med 2021;203:A2673.
40. Carson JL, Terrin ML, Magaziner J, et al. Transfusion trigger trial for functional outcomes in cardiovascular patients undergoing surgical hip fracture repair (FOCUS). Transfusion 2006;46:2192-206. [Crossref] [PubMed]
41. Chen TH, Shih JY, Shih JJ. Early Percutaneous Heparin-Free Veno-Venous Extra Corporeal Life Support (ECLS) is a Safe and Effective Means of Salvaging Hypoxemic Patients with Complicated Chest Trauma. Acta Cardiol Sin 2016;32:96-102. [PubMed]
42. Murphy DA, Hockings LE, Andrews RK, et al. Extracorporeal membrane oxygenation-hemostatic complications. Transfus Med Rev 2015;29:90-101. [Crossref] [PubMed]
43. Sniderman J, Monagle P, Annich GM, et al. Hematologic concerns in extracorporeal membrane oxygenation. Res Pract Thromb Haemost 2020;4:455-68. [Crossref] [PubMed]
44. Musumeci L, Aqil A, Jacques N, et al. A novel antithrombotic coating for blood-contacting medical devices. ISTH 2019. Accessed on 10 January 2023.
45. Muellenbach RM, Kredel M, Kunze E, et al. Prolonged heparin-free extracorporeal membrane oxygenation in multiple injured acute respiratory distress syndrome patients with traumatic brain injury. J Trauma Acute Care Surg 2012;72:1444-7. [Crossref] [PubMed]
46. Bakhtiary F, Keller H, Dogan S, et al. Venoarterial extracorporeal membrane oxygenation for treatment of cardiogenic shock: clinical experiences in 45 adult patients. J Thorac Cardiovasc Surg 2008;135:382-8. [Crossref] [PubMed]
47. Cahill CM, Blumberg N, Schmidt AE, et al. Implementation of a Standardized Transfusion Protocol for Cardiac Patients Treated With Venoarterial Extracorporeal Membrane Oxygenation Is Associated With Decreased Blood Component Utilization and May Improve Clinical Outcome. Anesth Analg 2018;126:1262-7. [Crossref] [PubMed]
48. Esper SA, Bermudez C, Dueweke EJ, et al. Extracorporeal membrane oxygenation support in acute coronary syndromes complicated by cardiogenic shock. Catheter Cardiovasc Interv 2015;86:S45-50. [Crossref] [PubMed]
49. Fagnoul D, Taccone FS, Belhaj A, et al. Extracorporeal life support associated with hypothermia and normoxemia in refractory cardiac arrest. Resuscitation 2013;84:1519-24. [Crossref] [PubMed]
50. Formica F, Avalli L, Colagrande L, et al. Extracorporeal membrane oxygenation to support adult patients with cardiac failure: predictive factors of 30-day mortality. Interact Cardiovasc Thorac Surg 2010;10:721-6. [Crossref] [PubMed]
51. Hryniewicz K, Sandoval Y, Samara M, et al. Percutaneous Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock Is Associated with Improved Short- and Long-Term Survival. ASAIO J 2016;62:397-402. [Crossref] [PubMed]
52. Lamarche Y, Cheung A, Ignaszewski A, et al. Comparative outcomes in cardiogenic shock patients managed with Impella microaxial pump or extracorporeal life support. J Thorac Cardiovasc Surg 2011;142:60-5. [Crossref] [PubMed]
53. Li CL, Wang H, Jia M, et al. The early dynamic behavior of lactate is linked to mortality in postcardiotomy patients with extracorporeal membrane oxygenation support: A retrospective observational study. J Thorac Cardiovasc Surg 2015;149:1445-50. [Crossref] [PubMed]
54. Loforte A, Marinelli G, Musumeci F, et al. Extracorporeal membrane oxygenation support in refractory cardiogenic shock: treatment strategies and analysis of risk factors. Artif Organs 2014;38:E129-41. [Crossref] [PubMed]
55. Marasco SF, Vale M, Pellegrino V, et al. Extracorporeal membrane oxygenation in primary graft failure after heart transplantation. Ann Thorac Surg 2010;90:1541-6. [Crossref] [PubMed]
56. Mikus E, Tripodi A, Calvi S, et al. CentriMag venoarterial extracorporeal membrane oxygenation support as treatment for patients with refractory postcardiotomy cardiogenic shock. ASAIO J 2013;59:18-23. [Crossref] [PubMed]
57. Mohite PN, Kaul S, Sabashnikov A, et al. Extracorporeal life support in patients with refractory cardiogenic shock: keep them awake. Interact Cardiovasc Thorac Surg 2015;20:755-60. [Crossref] [PubMed]
58. Muehrcke DD, McCarthy PM, Stewart RW, et al. Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock. Ann Thorac Surg 1996;61:684-91. [Crossref] [PubMed]
59. Opfermann P, Bevilacqua M, Felli A, et al. Prognostic Impact of Persistent Thrombocytopenia During Extracorporeal Membrane Oxygenation: A Retrospective Analysis of Prospectively Collected Data From a Cohort of Patients With Left Ventricular Dysfunction After Cardiac Surgery. Crit Care Med 2016;44:e1208-18. [Crossref] [PubMed]
60. Staudacher DL, Biever PM, Benk C, et al. Dual Antiplatelet Therapy (DAPT) versus No Antiplatelet Therapy and Incidence of Major Bleeding in Patients on Venoarterial Extracorporeal Membrane Oxygenation. PLoS One 2016;11:e0159973. [Crossref] [PubMed]
61. Müller T, Philipp A, Luchner A, et al. A new miniaturized system for extracorporeal membrane oxygenation in adult respiratory failure. Crit Care 2009;13:R205. [Crossref] [PubMed]
62. Ang AL, Teo D, Lim CH, et al. Blood transfusion requirements and independent predictors of increased transfusion requirements among adult patients on extracorporeal membrane oxygenation -- a single centre experience. Vox Sang 2009;96:34-43. [Crossref] [PubMed]
63. Agerstrand CL, Burkart KM, Abrams DC, et al. Blood conservation in extracorporeal membrane oxygenation for acute respiratory distress syndrome. Ann Thorac Surg 2015;99:590-5. [Crossref] [PubMed]
64. Rosenberg EM, Chambers LA, Gunter JM, et al. A program to limit donor exposures to neonates undergoing extracorporeal membrane oxygenation. Pediatrics 1994;94:341-6. [Crossref] [PubMed]
65. Tolksdorf B, Schmeck J, Osika A, et al. Autotransfusion during extracorporeal membrane oxygenation. Int J Artif Organs 2000;23:840-4. [Crossref] [PubMed]
66. Fischer MO, Guinot PG, Debroczi S, et al. Individualised or liberal red blood cell transfusion after cardiac surgery: a randomised controlled trial. Br J Anaesth 2022;128:37-44. [Crossref] [PubMed]
67. Zeroual N, Blin C, Saour M, et al. Restrictive Transfusion Strategy after Cardiac Surgery. Anesthesiology 2021;134:370-80. [Crossref] [PubMed]
68. Ostadal P, Mlcek M, Gorhan H, et al. Electrocardiogram-synchronized pulsatile extracorporeal life support preserves left ventricular function and coronary flow in a porcine model of cardiogenic shock. PLoS One 2018;13:e0196321. [Crossref] [PubMed]
69. Kanagarajan D, Heinsar S, Gandini L, et al. Preclinical Studies on Pulsatile Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review. ASAIO J 2023;69:e167-80. [Crossref] [PubMed]
70. Suwalski P, Staromłyński J, Brączkowski J, et al. Transition from Simple V-V to V-A and Hybrid ECMO Configurations in COVID-19 ARDS. Membranes (Basel) 2021;11:434. [Crossref] [PubMed]
71. Meani P, Gelsomino S, Natour E, et al. Modalities and Effects of Left Ventricle Unloading on Extracorporeal Life support: a Review of the Current Literature. Eur J Heart Fail 2017;19:84-91. [Crossref] [PubMed]