Asian Journal of Transfusion Science
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ORIGINAL ARTICLE  
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A retrospective study to assess the transfusion requirements of patients on extracorporeal membrane oxygenation support


 Department of Transfusion Medicine, Sree Chitra Tirunal Institute for Medical Sciences, Thiruvananthapuram, Kerala, India

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Date of Submission26-Apr-2022
Date of Decision06-Jul-2022
Date of Acceptance07-Aug-2022
Date of Web Publication12-Dec-2022
 

   Abstract 

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a mode of therapy initiated for patients with cardiac and/or respiratory failure. Blood transfusion plays a significant role in the management of ECMO patients. In this study, pediatric patients were all cyanotic and transfusion requirements of cyanotic patients differ from other critically ill patients. This study has been conducted to assess the daily transfusion requirements of such group of patients to frame future transfusion policies.
AIMS AND OBJECTIVES: This study was undertaken to assess the daily transfusion requirements of ECMO patients with various indications for ECMO initiation. Our aim was to formulate institutional transfusion policies for paediatric and adult patients on ECMO.
MATERIALS AND METHODS: A three years retrospective study was undertaken with 20 study participants. Transfusion requirements were analyzed with regard to the number of days on ECMO support and indications for ECMO initiation. Iatrogenic blood loss/day was assessed among paediatric age group.
RESULTS: Maximum transfusions with PRBC, FFP, and platelet concentrates occurred during the initial 7 days on ECMO. The median packed red cell requirement and FFP requirements for pediatric age group was 1260 ml (IQR = 360-3580) and 900 ml (IQR=150-4650) ml respectively. The median platelet and cryoprecipitate requirements were 450 ml (80-1610) and 120 ml (0.00-600) respectively. The median survival was 8 days (IQR=5.961-10.039).
CONCLUSION: Transfusion requirements would largely depend upon the clinical status of the patient and therefore, with a smaller number of participants it is difficult to make generalised recommendations. However, the present study could help us to frame institutional-based transfusion support policies for ECMO patients.

Keywords: Bleeding, blood transfusion, coagulopathy, extracorporeal membrane oxygenation, thrombosis


How to cite this URL:
Mani A, Nair AR, Gupta D. A retrospective study to assess the transfusion requirements of patients on extracorporeal membrane oxygenation support. Asian J Transfus Sci [Epub ahead of print] [cited 2023 Jan 28]. Available from: https://www.ajts.org/preprintarticle.asp?id=363232



   Introduction Top


Extracorporeal membrane oxygenation (ECMO) is a treatment modality that has been used to treat critically ill patients with cardiac and/or respiratory failure to support both the failing heart and lungs. The first successful ECMO was published in 1972 in a trauma patient who developed acute respiratory distress syndrome and this was followed by the use in cardiogenic shock in 1973, and in 1975 for meconium aspiration syndrome.[1] The mode of ECMO is defined by the location of the access and return cannula. ECMO involves accessing deoxygenated venous blood from the systemic circulation, pressurizing it using a pump and passing it through a membrane oxygenator, then returning it to either the venous side of the circulation (the right atrium) in veno-venous ECMO (VV ECMO or respiratory ECMO) or to the arterial circulation (typically the aorta) in veno-arterial ECMO (VA ECMO or cardiac ECMO).[2]

Blood and blood components are vital constituents for any patient receiving ECMO support not only to prime the circuit but also to meet the extensive transfusion requirements. ECMO initiation necessitates an increasing demand for all blood components including packed red cell concentrates (PRBC), fresh frozen plasma (FFP), cryoprecipitate, and platelet concentrates. The transfusion of patients on ECMO support stands challenging due to a variety of reasons. There are no clear-cut transfusion guidelines or sufficient data from clinical trials to frame a uniform transfusion protocol for this category of patients. Hence, the transfusion policies are largely institution-specific.

Appropriate transfusion thresholds for blood component transfusions are uncertain and ECMO centers are thereby following center-specific thresholds.[3] Patients kept on ECMO support is bound to get massively transfused due to reasons such as worsening clinical condition, the need for iatrogenic anticoagulation in the ECMO circuit, and platelet dysfunction leading to bleeding and fatal complications. In addition to this, there are recent studies that suggest a restrictive transfusion strategy to be more safe and effective.[4]

The Extracorporeal Life Support Organization (ELSO), is an international organization composed of ECMO centers worldwide with an effort to create ECMO anticoagulation and blood product management guidelines for newborns, children, and adults. These guidelines recommend the maintenance of a hematocrit of 35%–40%, FFP transfusion for bleeding patients or in case the international normalized ratio (INR) >1.5 to 2, cryoprecipitate transfusion for fibrinogen levels <100–150 mg/dL, and platelet transfusion threshold to maintain a platelet count >100,000/μl.[5] All these recommendations are rather based on local or institutional experiences and not as per optimal transfusion requirements of each and every patient.

The exposure to the artificial, nonendothelialized ECMO circuit results in the activation of platelets and coagulation cascade. Extensive cellular activation, accompanied by inflammatory changes could disturb normal homeostasis. High doses of unfractionated heparin (UFH) to prevent circuit thrombosis induce platelet disruption owing to an increased demand for platelet transfusions.[6] There can be frequent platelet transfusions due to the continued disruption and resultant thrombocytopenia. Bleeding complications are most often life-threatening, and therefore, there will be a higher platelet transfusion thresholds on ECMO as compared to other patients.[2]

Our center has got a well-established cardiothoracic and vascular surgery unit that performs the most complicated pediatric cardiac surgeries along with routine adult cardiac and vascular surgeries. The vast majority of the pediatric patients admitted to our institute are cyanotic congenital heart disease (CCHD) patients requiring intracardiac repair surgery. The complexity of the clinical condition as such and complications following major surgical procedures can lead the patient to be on ECMO support. Initiation of ECMO support is usually on an emergency basis and the patient will be on increased transfusion demands with blood and blood components eventually.

The transfusion support of cyanotic patients on ECMO support differs to a greater extent from other critically ill patients due to the need to maintain better oxygen saturation levels. Unfortunately, the red cell and platelet transfusion thresholds are poorly defined for such a group of patients leading to irrational use of blood and blood components. This study is undertaken for the assessment of the transfusion requirements of ECMO patients in view to define a uniform protocol to guide the transfusion support for future transfusions. This is high time to make evidence-based policies to enhance the rational use of blood and blood components.

Objectives of the study

This study was undertaken to analyze the various indications for ECMO initiation and to assess the daily transfusion requirements, thereby correlating transfusion requirements with outcome of patients. Our final goal was to frame future transfusion policies for pediatric and adult patients on ECMO support.


   Materials and Methods Top


Ethical clearance was obtained from the Institutional Ethics Committee-SCT/IEC/1590/DECEMBER-2020 for the conduction of the study. This is a retrospective observational study involving all patients who required ECMO support at our institution over 3 years (January 2017–January 2020). The ECMO circuit was pre-treated with either colloids-like albumin or crystalloids like Ringer's Lactate and then PRBC was added to attain hematocrit of around 40%. Calcium gluconate and sodium bicarbonate were added to normalize the ionized calcium levels and to maintain circuit pH. UFH (100 U/kg) bolus was administered to all patients followed by repeated doses of heparin to maintain activated clotting time (ACT) of 180 ± 220 s.[7] ACT was measured at the bedside using the Hemotek® system (Medtronic, Minneapolis, Minn., USA).

Patient details were obtained from the hospital medical records which included their age, weight, diagnosis, investigation reports, indications for ECMO initiation, elective/emergency ECMO, type of ECMO, length of ECMO, and daily transfusion requirements during ECMO support. Additional details included the length of ventilator support, length of ICU and total hospital stay, and survival outcomes. Transfusion requirements were analyzed with regard to the age, weight, number of days on ECMO support, and indications for ECMO initiation. Iatrogenic blood loss/day was assessed among the pediatric age group. This calculation was made by counting the total number of blood samples drawn each day and the volume of each vacutainer tube.

Statistical analysis

Numerical data were expressed as mean ± standard deviation and categorical data as frequencies (n) and percentages (%). Association between categorical variables was analyzed using the Pearson-Chi-squared test. Continuous variables were compared between two groups using Student's t-test and with more than two groups with ANOVA test. All statistical tests were two-sided and a P < 0.05 was considered statistically significant. Survival analysis was performed with Kaplan–Meier survival analysis and data analysis was performed using SPSS (version 23.0) : SPSS inc. Chicago, USA.


   Results Top


We had a total of 20 patients who required ECMO support over 3 years. This includes 75% (n = 15) pediatric and 25% (n = 5) adult patients. Out of these 20 patients, 55% (n = 11) of patients were males and 45% (n = 9) were females. All patients underwent VA – Central type (veno arterial) of ECMO support. Right atrium – Aorta cannulation was performed as the ECMO initiation was during the open cardiac repair. In this study, 80% (n = 16) of the patients were put on ECMO support for cardiac indications and only 20% of the patients had respiratory indications (n = 4). Hence, statistical significance between indications for ECMO initiation and transfusion requirements could not be commented on. All cardiac indications were severe enough to cause cardiogenic shock and resultant cardiac arrest to initiate ECMO [Table 1].
Table 1: Various indications to initiate extracorporeal membrane oxygenation support

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The median age of pediatric patients was 7 months (IQR = 2–24) and that of adult patients was 46 years (IQR = 21–77.5). The median weight of pediatric patients was 5 kg (IQR = 3.75–8) and that of adult patients was 68 kg (IQR = 52–77.5). The median iatrogenic blood loss/day was 12.5 ml (IQR = 10–24). The median SPO2 of pediatric patients was 84% (IQR = 70–88) and that of adult patients was 98.4% (IQR = 97–100).

The median hospital stay was 15 days (IQR = 10.25–28) and the median ICU stay was 14 days (IQR = 9.25–24.50). The median stay on ventilator support was 11 days (IQR = 7–17) and that on ECMO support was 6.50 days (IQR = 3–8).

Mean hematological parameters on extracorporeal membrane oxygenation on Day 1 and across the entire hospital stay were as follows

The mean hemoglobin (Hb) on day 1 was 11.14 ± 1.77 g/dl and mean hematocrit (Hct) was 33.91 ± 5.2%. The median platelet count on day 1 was 96,500/μl (IQR = 30,000 – 2.34). The mean prothrombin time (PT) was 33 ± 13.7 s, mean INR was 2.77 ± 1.21 s, and mean activated partial thromboplastin time (aPTT) was 84.84 ± 35.49 s.

To demonstrate the trend in hematological parameters, initial 7 days of ECMO support have been taken into consideration as the majority of the changes were observed during this period [Figure 1], [Figure 2], [Figure 3]. The mean Hb = 13.4 ± 3.15 g/dl, mean Hct = 40.98 ± 10.46%, median platelet count = 1.69 lakhs/μl (IQR = 1.3 – 2.4), mean PT = 21.6 ± 8.1 s, mean INR = 1.62 ± 0.81, and mean aPTT = 43.8 ± 8.4 s.
Figure 1: Transition of hemoglobin and hematocrit over 7 days on ECMO. ECMO = Extracorporeal membrane oxygenation

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Figure 2: Transition of platelet count over 7 days on ECMO. ECMO = Extracorporeal membrane oxygenation

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Figure 3: Transition of PT-INR and aPTT over 7 days on ECMO. ECMO = Extracorporeal membrane oxygenation, PT-INR = Prothrombin time-international normalized ratio, aPTT = Activated partial thromboplastin time

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Transfusion requirements during extracorporeal membrane oxygenation support

Maximum blood component therapy with PRBC, FFP, and platelets occurred during the initial 7 days. Fall in hemoglobin and hematocrit were observed from the very first day of ECMO initiation and the increment observed on day 3 was due to PRBC transfusion [Figure 1]. Only transient increments were observed even with transfusion support and hemoglobin levels continued to drop.

Coagulation profiles of ECMO patients were extremely dynamic and unpredictable. Platelet transfusion constituted a crucial part of blood component therapy as there was a drastic decline in platelet count as days progressed. Despite repeated platelet transfusions, platelet counts continued to decline [Figure 2]. Even though PT values were relatively stable, aPTT remained almost always >120 s [Figure 3]. Platelet dysfunction coupled with anticoagulation with high doses of UFH in the ECMO circuit necessitated frequent FFP and cryoprecipitate transfusions.

Even though survivals of adult ECMO patients were poor compared to pediatric patients, the transfusion requirements were relatively similar. For pediatric patients, PRBC's and FFP's constituted the majority of the transfusions and for adult patients, major transfusion support was with PRBC's. All blood components were transfused hand in hand as the patients on ECMO were purely transfusion-dependent [Table 2] and [Table 3]. There was an increased demand to transfuse platelets, FFP, and cryoprecipitate to prevent, and treat coagulopathy as the duration of ECMO support advanced.
Table 2: Blood products as number of units transfused

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Table 3: Transfusion requirements of extracorporeal membrane oxygenation patient blood component wise

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Outcome of patients

We have observed 60% mortality of patients on ECMO support (n = 15) and 100% mortality for adult patients (n = 5). All the patients who survived ECMO support belonged to the pediatric age group (n = 5). Out of the 15 patients who expired, 10 were pediatric patients and among them, three children could be weaned from ECMO. However, these patients also expired due to sepsis with multi-organ dysfunction syndrome later on. The median number of survival days on ECMO was found to be 8 days (IQR = 5.961–10.039) using Kaplan–Meier survival analysis [Figure 4]. We could observe the survival on day 3 to be 89.5% where as it dropped to 46.5% by day 8. The survival rate by day 10 was 18.6% and this declined to 9.3% by day 23. We could not obtain any statistical significance between the transfusion requirements and the outcome of ECMO patients (P = 0.537).
Figure 4: Kaplan–Meier survival analysis plot of ECMO patients. ECMO = Extracorporeal membrane oxygenation

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Causes of mortality

Pediatric patients were cyanotic and baseline oxygen saturation was low, requiring transfusion support during the surgical procedure itself to improve oxygen-carrying capacity. A major cause of mortality was found to be cardiopulmonary arrest followed by severe biventricular dysfunction among 64.7% (n = 11) of pediatric patients [Table 4]. The major cause of mortality was sepsis with multi-organ dysfunction syndrome among 17.7% (n = 3) of adult patients.
Table 4: Various causes of mortality on extracorporeal membrane oxygenation

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   Discussion Top


Blood transfusion during extracorporeal support typically occurs for reasons such as circuit priming, restoration of oxygen-carrying capacity, maintenance of a hemostatic balance, and treatment of hemorrhagic complications.[8] Exposure of blood to the artificial, nonendothelialized surface of an ECMO circuit results in the initiation of the coagulation cascade, cellular activation, platelet activation, disruption, and increased inflammation, which disturbs normal homeostasis.[7],[9],[10],[11]

The reason for ECMO initiation was a cardiac failure among most of the patients in our study. Platelets sustain both quantitative and qualitative defects to shear stress in extracorporeal circuits. This can result in contact activation and release of von Willebrand factor (VWF) with subsequent platelet adhesion through GPIb and expression of GPIIb/IIIa receptors.[12] As the number of days on ECMO support advanced a drop in platelet count became more and more evident. We could observe a steady decline in platelet count over the initial 7 days and this necessitated repeated platelet transfusions.

Anticoagulation is necessary to maintain the patency of the circuit and reduce thrombotic complications. UFH remains the most widely utilized anticoagulant on patients with ECMO support.[6] High doses of heparin in the circuit can lead to heparin-induced thrombocytopenia (HIT) and can proceed into iatrogenic bleeding complications. The vast majority of ECMO centers employ ACT as the preferred anticoagulation monitoring tool. ACT testing has several disadvantages; it can be prolonged in cases of thrombocytopenia, platelet dysfunction, elevated D-dimers, low fibrinogen, other coagulation factor deficiencies, hypothermia, or hemodilution, and can be decreased in hypercoagulable states. It is often difficult to comment HIT for ECMO patients, as thrombocytopenia is multifactorial.

Thrombosis is a well-known complication of ECMO support. In the most recent annual ELSO report, clots were reported to occur in the oxygenator in nearly 13% of patients. Additional clots in other parts of the circuit were more common in patients on ECMO for cardiac support than those for respiratory support. Central nervous system infarction was reported to occur in up to 3.5% of patients.[2] In our study, we could not observe any thrombotic complications, but bleeding manifestations such as epistaxis and generalized ecchymosis were common.

Although the circuit is heparin-coated with extra doses of additional heparin, bleeding remains a major concern.[13] It is the leading contributor to mortality in ECMO patients in most of the large case series and registry data.[14] ECMO patients are critically ill patients who already have an imbalance of their procoagulant and anticoagulant pathways. In addition to this, a system causing platelet activation, inflammation, and consumption of clotting factors, utilizing large-bore arterial, and venous access will contribute to an increased risk of bleeding.[2]

Disseminated intravascular coagulation was another dreadful complication that we observed on patients on ECMO support. Once the patient starts to bleed it becomes hard to control the active hemorrhage and the patient will ultimately end up in hypovolemic shock. Bleeding episodes were managed with FFP, cryoprecipitate, platelet concentrates, and PRBC's. Transfusion therapy was always under heparin coverage as thrombotic complications were expected if heparin was withheld.

Hemolysis is common during ECMO support and the factors such as shear stress, physical properties of the ECMO circuit, sublethal damage to erythrocytes, the roller pump, changes in blood volume, and pressure changes within the oxygenator have all been implicated for its development. Intravascular hemolysis will be characterized by an increase in plasma-free hemoglobin and can ultimately lead to renal failure and multi-organ failure.[15] Packed red cell transfusion support was necessary to maintain the hemodynamics as the majority of patients in our study were operated for CCHDs.

RBC transfusion has been closely linked with an increase in morbidity and mortality statistics across a broad patient population.[16] Exposure to allogeneic blood product is an inevitable aspect of ECMO therapy. Beyond the initial blood prime to the ECMO circuit, replacement blood products are frequently used in response to untoward bleeding, thrombosis, phlebotomy, and/or ongoing hemolysis.[17] Thus, repeated exposure to allogeneic blood and blood components is inherent to ECMO therapy and may introduce additional transfusion-related morbidity and mortality risk.

Due to the lack of widespread availability and huge expenses of ECMO facilities, the number of patients who are put on ECMO support is less. In India, only very few hospitals have got ECMO facilities and one of those centers is ours. Due to the abovestated reasons, there were only 20 patients in our study over 3 years. The mortality rate of patients on ECMO support is very high and was observed to be 60% in our study. Another study also demonstrated an in-hospital mortality rate of almost 77% for ECMO patients.[18]

Even though the hematological parameters were near normal, patients were prophylactically or therapeutically transfused with blood components as demanded by the clinical condition. In our study, patients with a platelet count of 100,000/μl also exhibited mucocutaneous bleeding manifestations probably due to platelet dysfunction. Due to anticoagulation, bleeding manifestations were likely and aPTT values were >120 s majority of the time. To prevent major bleeding, FFP transfusions were administered prophylactically as well. Packed red cell transfusions were used not only to maintain hematocrit but also to maintain effective oxygenation and to compensate for volume loss at times of hemorrhage.

One of the main goals of our study was to design a separate transfusion support policy for patients on ECMO support. Even though we had only 20 patients, the data collected were for 3 years. To design a transfusion policy from the small number of patients for future reference was difficult as this may not always reflect the entire ECMO patients who require transfusions. However, from the current transfusion requirements, we designed a transfusion policy in such a way that all ECMO patients could be supported with blood group compatible blood components at any point of time.

We could not predict the transfusion thresholds from the hematological parameters as transfusions were not always based on laboratory values. However, we made it mandatory to be intimated to the blood center as early as possible whenever ECMO has been initiated. Blood inventory management would be planned accordingly and in case any blood group-specific blood component is insufficient, blood donors would be arranged from our voluntary donor registry. In addition to PRBC's and FFP's, platelet concentrates and cryoprecipitate would be prepared and stored as required. Whenever we are intimated that the patient is put on ECMO support, our blood inventory would be ready with blood group-specific three PRBC units, two units of FFP, two units of platelet concentrates, and two cryoprecipitate units.

In case, the requirement on a given day is more than what is expected, the blood center needs to be informed to make it convenient to arrange for more blood components as per requirement. However, the transfusion requirements would depend on multiple factors such as the clinical condition of the patient and complexity of the surgical procedure, bleeding on the ECMO circuit, and heparin-induced thrombocytopenia. Patients on ECMO support would undoubtedly require multiple transfusions and there should always remain active communication between the clinical side and blood center.


   Conclusion Top


Special circumstances such as ECMO necessitate the need for an efficient and well-coordinated transfusion medicine department for the provision of adequate blood and blood products at the right time with minimal turnaround time. There should be written guidelines and separate massive transfusion protocols for special cases such as congenital cyanotic heart disease patients on ECMO. The transfusion services should be notified as soon as possible once the patient is put on ECMO support and there should be round the clock unlimited supply of blood and blood products from the transfusion services.

Acknowledgments

We also thank the Director, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Transfusion Medicine for permitting us to perform the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Gray BW, Haft JW, Hirsch JC, Annich GM, Hirschl RB, Bartlett RH. Extracorporeal life support: Experience with 2,000 patients. ASAIO J 2015;61:2-7.  Back to cited text no. 1
    
2.
Murphy DA, Hockings LE, Andrews RK, Aubron C, Gardiner EE, Pellegrino VA, et al. Extracorporeal membrane oxygenation-hemostatic complications. Transfus Med Rev 2015;29:90-101.  Back to cited text no. 2
    
3.
Dalton HJ, Reeder R, Garcia-Filion P, Holubkov R, Berg RA, Zuppa A, et al. Factors associated with bleeding and thrombosis in children receiving extracorporeal membrane oxygenation. Am J Respir Crit Care Med 2017;196:762-71.  Back to cited text no. 3
    
4.
Smith A, Hardison D, Bridges B, Pietsch J. Red blood cell transfusion volume and mortality among patients receiving extracorporeal membrane oxygenation. Perfusion 2013;28:54-60.  Back to cited text no. 4
    
5.
Guidelines. ELSOA. Extracorporeal Life Support Organization (ELSO) Anticoagulation Guideline Table. Ann Arbor MI , USA: ELSO; 2014. p. 1-17.  Back to cited text no. 5
    
6.
Andrews J, Winkler AM. Challenges with navigating the precarious hemostatic balance during extracorporeal life support: Implications for coagulation and transfusion management. Transfus Med Rev 2016;30:223-9.  Back to cited text no. 6
    
7.
Arnold P, Jackson S, Wallis J, Smith J, Bolton D, Haynes S. Coagulation factor activity during neonatal extra-corporeal membrane oxygenation. Intensive Care Med 2001;27:1395-400.  Back to cited text no. 7
    
8.
Berkowitz I, Pronovost P. Extracorporeal membrane oxygenation: An international Survey. Pediatr Crit Care Med 2013;14:1-15.  Back to cited text no. 8
    
9.
Annich GM. Extracorporeal life support: The precarious balance of hemostasis. J Thromb Haemost 2015;13 Suppl 1:S336-42.  Back to cited text no. 9
    
10.
Urlesberger B, Zobel G, Zenz W, Kuttnig-Haim M, Maurer U, Reiterer F, et al. Activation of the clotting system during extracorporeal membrane oxygenation in term newborn infants. J Pediatr 1996;129:264-8.  Back to cited text no. 10
    
11.
McManus ML, Kevy SV, Bower LK, Hickey PR. Coagulation factor deficiencies during initiation of extracorporeal membrane oxygenation. J Pediatr 1995;126:900-4.  Back to cited text no. 11
    
12.
Da Q, Teruya M, Guchhait P, Teruya J, Olson JS, Cruz MA. Free hemoglobin increases von willebrand factor-mediated platelet adhesion in vitro: Implications for circulatory devices. Blood 2015;126:2338-41.  Back to cited text no. 12
    
13.
Massetti M, Tasle M, Le Page O, Deredec R, Babatasi G, Buklas D, et al. Back from irreversibility: Extracorporeal life support for prolonged cardiac arrest. Ann Thorac Surg 2005;79:178-83.  Back to cited text no. 13
    
14.
Paden ML, Conrad SA, Rycus PT, Thiagarajan RR, ELSO Registry. Extracorporeal life support organization registry report 2012. ASAIO J 2013;59:202-10.  Back to cited text no. 14
    
15.
Betrus C, Remenapp R, Charpie J, Kudelka T, Brophy P, Smoyer WE, et al. Enhanced hemolysis in pediatric patients requiring extracorporeal membrane oxygenation and continuous renal replacement therapy. Ann Thorac Cardiovasc Surg 2007;13:378-83.  Back to cited text no. 15
    
16.
Salpeter SR, Buckley JS, Chatterjee S. Impact of more restrictive blood transfusion strategies on clinical outcomes: A meta-analysis and systematic review. Am J Med 2014;127:124-31.e3.  Back to cited text no. 16
    
17.
Stiller B, Lemmer J, Merkle F, Alexi-Meskishvili V, Weng Y, Hübler M, et al. Consumption of blood products during mechanical circulatory support in children: Comparison between ECMO and a pulsatile ventricular assist device. Intensive Care Med 2004;30:1814-20.  Back to cited text no. 17
    
18.
Shimizu K, Ogura H. Is the 77.1% rate of in-hospital mortality in patients receiving venoarterial extracorporeal membrane oxygenation really that high? Crit Care 2016;20:202.  Back to cited text no. 18
    

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Correspondence Address:
Amita Radhakrishnan Nair,
Department of Transfusion Medicine, Sree Chitra Tirunal Institute for Medical Sciences, Thiruvananthapuram, Kerala
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.ajts_52_22



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