Extracorporeal Membrane Oxygenation Anticoagulation Research Articles

Anticoagulation Management in V-V ECMO Patients: A Multidisciplinary Pragmatic Protocol

(1) Background: Extracorporeal membrane oxygenation (ECMO) is a complex procedure affecting both the risk of thrombosis and bleeding. High-quality data to personalize anticoagulation management in ECMO are lacking, resulting in a high variability in practice among centers. For this reason, we review coagulation methods and monitoring and share a pragmatic proposal of coagulation management, as performed in our high-volume ECMO Referral Centre; (2) Methods: We revised the anticoagulation options and monitoring methods available for coagulation management in ECMO through PubMed search based on words including “anticoagulation,” “coagulation assays,” “ECMO,” “ELSO,” and “ISTH”; (3) Results: Actual revision of the literature was described as our routine practice regarding ECMO anticoagulation and monitoring; (4) Conclusions: No coagulation test is exclusively predictive of bleeding or thrombotic risk in patients undergoing ECMO support. An approach that allows for a tailored regimen of anticoagulation (regardless of agent used) and monitoring is mandatory. To accomplish this, we propose that the titration of anticoagulation therapies should include multiple laboratory tests, including anti-Xa, aPTT, ACT, viscoelastic tests, AT levels, platelet count, fibrinogen, and FXIII levels. Anticoagulation regimens should be tailored to a specific patient and personalized based on this complex array of essays.

Summary of the best evidence for anticoagulation and bleeding risk management in patients with extracorporeal membrane oxygenation

To evaluate and summarize the relevant evidence of anticoagulation and bleeding risk management in patients with extracorporeal membrane oxygenation (ECMO), and provide the evidence-based basis for the management of anticoagulation and bleeding during ECMO treatment. According to the evidence "6S" pyramid model, all evidence on ECMO anticoagulation management and bleeding risk was searched in relevant databases, organizations and guideline websites at home and abroad. Evidence types included guidelines, expert consensus, systematic evaluation, Meta-analysis and original study. The search time limit was from May 31, 2012 to May 31, 2022. Two researchers with evidence-based research background conducted independent literature quality evaluation of the retrieved evidence, and the evidence that met the quality standards was extracted and summarized based on the opinions of industry experts. A total of 315 articles were retrieved, and 13 articles were included, including 3 guidelines, 6 expert consensus, and 4 Meta-analysis. A total of 27 best evidences were summarized from 7 aspects, including the selection of ECMO anticoagulation, anticoagulation in priming, anticoagulation in operation, anticoagulation monitoring, bleeding and treatment, thrombosis and treatment, and prevention and management of terminal limb ischemia. This study provides evidence-based basis for bleeding prevention and anticoagulant management in ECMO patients. It is recommended to selectively apply the best evidence after evaluating the clinical environmental conditions of medical institutions, so as to improve the prognosis of ECMO patients.

Anticoagulation with Intravenous Direct Thrombin Inhibitors in Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review of the Literature.

Although intravenous (IV) direct thrombin inhibitors (DTI) have gained interest in pediatric extracorporeal membrane oxygenation (ECMO), dosing and safety information is limited. The objective of this systematic review was to characterize DTI types, dosing, monitoring, and outcomes (bleeding and thromboembolic) in pediatric ECMO patients managed with IV DTIs. We conducted searches of MEDLINE (Ovid) and Embase (Elsevier) from inception through December 2022. Case reports, retrospective studies, and prospective studies providing per-patients or summary data for patient(s) <18 years of age receiving IV DTI for ECMO anticoagulation were included. Study selection and data extraction were conducted independently by two reviewers. A total of 28 studies: 14 case reports, 13 retrospective studies, and 1 prospective study were included, totaling 329 patients. Bivalirudin was utilized in 318 (96.7%), argatroban in 9 (2.7%), and lepirudin in 2 (0.6%) patients. Infusion dosing included: bivalirudin 0.14 ± 0.37 mg/kg, argatroban 0.69 ± 0.73 µg/kg/min, lepirudin 0.14 ± 0.02 mg/kg/h. Laboratory monitoring tests utilized were the activated clotting time, activated partial thromboplastin time (aPTT), diluted thrombin time, and thromboelastography measures. The aPTT was utilized in most patients (95%). Thromboembolism, bleeding, or death were observed in 17%, 17%, and 23% of bivalirudin, argatroban, and lepirudin patients, respectively. Bivalirudin appears to be the most frequently used DTI in pediatric ECMO. Dosing and laboratory monitoring varied, and bleeding and thromboembolic events were reported in 17% of patients. Prospective studies are warranted to establish dosing, monitoring, safety, and efficacy of bivalirudin and other IV DTI in pediatric ECMO.

Is it time to switch to bivalirudin for ECMO anticoagulation?

For decades, unfractionated heparin (hereafter, heparin) has been the primary anticoagulant used for extracorporeal membrane oxygenation (ECMO) support. More recently, however, bivalirudin, a direct thrombin inhibitor, has emerged as an alternative. This systematic review based on PRISMA guidelines, aims to summarize 16 comparative studies and 8 meta-analysis and review articles published from January, 2011 till May, 2023 which directly compares ECMO courses using heparin versus bivalirudin as the anticoagulant. While this comparison is complicated by the lack of a standardized definition of major bleeding or thrombosis, our overall findings suggest there is no statistical difference between heparin and bivalirudin in incidence of bleeding and thrombosis. That said, some studies found a statistical significance favoring bivalirudin in reducing major bleeding, thrombosis, and the need for transfusions. We also offer essential guidance for appropriately selecting an anticoagulant and monitoring its effect in ECMO settings.

Review of anticoagulation considerations in extracorporeal membrane oxygenation support.

Since its first success in 1975, extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for pulmonary and cardiopulmonary bypass. Use in adults has increased exponentially since the early 2000s, but despite thousands of international cannulations using both veno-arterial (VA) and veno-venous (VV) ECMO, there are still significant hemocompatibility-related adverse events. Current management of anticoagulation has been based on the Extracorporeal Life Support Organization guidance published in 2014 with recent updates published in 2022. Despite this guidance, there is still limited international consensus on how to manage anticoagulation in ECMO. For this review, we completed a comprehensive search of multiple electronic databases to identify studies pertaining to anticoagulation of adult patients on VV or VA-ECMO. The highest priority was given to sources that were prospective, randomized, controlled studies, but in the absence of such resources, observational studies, retrospective uncontrolled studies, and case series/reports were considered for inclusion. This document serves to provide a comprehensive review of the current understanding of management pertaining to anticoagulation relating to ECMO.

PEDS9: Bleeding in Pediatric Patients on Extracorporeal Membrane Oxygenation-Use of Procoagulant Factors

Background: Bleeding complications remain common in extracorporeal membrane oxygenation (ECMO) and can be associated with adverse outcomes. Effect of excessive shear stress on vasculature may increase bleeding risk associated with preferential loss of high molecular weight von Willebrand factor (high molecular weight (vWF) multimers; acquired vW syndrome, AVWS) and may also be associated with platelet dysfunction. Some pediatric patients may have a pre-existing increased risk of shear-related abnormalities which may further increase bleeding risk on ECMO. We aimed to review bleeding events requiring intervention in a pediatric ECMO cohort. Methods: Retrospective review of pediatric ECMO patients who underwent treatment of bleeding beyond simple transfusion in conjunction with ECMO anticoagulation consultation (EAC) between June 2020 and December 2022 was conducted. Results: Fifty patients required ECMO for 53 runs (52 VA, 2 VV, 1 VAV). Median weight was 4.3 kg (2.4-131 kg). Mean duration of ECMO was 11 days (2-97). 60% (30/50) of patients had congenital heart disease (CHD), and within these 30 patients, 27% of them had bleeding requiring procedural intervention. Ten patients with bleeding were screened for AVWS guided by EAC with 100% meeting criteria for AVWS. Platelet transfusions were administered as first line bleeding therapy with thrombocytopenia or platelet dysfunction and plasma or prothrombin complex concentrate (PCCC) in volume-sensitive patients for coagulopathy. With ongoing bleeding despite transfusion, antihemophilic factor/vWF complex (Humate P) was administered to 4 patients guided by EAC (figure 1). Of these 4 patients, 75% had CHD and 100% had valve abnormalities with 50% having new mechanical valves placed within 1 month prior to ECMO. Initial Humate P dose was given on mean day 14, with mean number of 8 doses. No circuit or mechanical valve thrombosis occurred. Platelet counts and function improved with a decrease in platelet transfusions and clinical bleeding in all patients following Humate P. Conclusion: Bleeding remains a common complication but is often multifactorial and may be difficult to determine specific etiologies. AVWS and thrombocytopenia commonly occur during pediatric ECMO. However, not all patients have clinical bleeding, such that additional risk factors may contribute to increased bleeding risk in these patients. Given impact of recurrent transfusions due to bleeding on morbidity and mortality, as well as cost consideration and potential thrombosis risk of vWF or PCCC supplementation, development of an expert-guided (EAC) algorithm for screening and treatment criteria for such agents appears to be safe, cost-effective and may be associated with decreased bleeding and transfusions. Further research into etiologies and consequences of ECMO-induced bleeding as well as treatment is needed.Figure 1. Algorithm for Assessment of Persistent Bleeding and Consideration of Humate P Administration (pilot).

Safety of low-dose anticoagulation in extracorporeal membrane oxygenation using the Permanent Life Support System: a retrospective observational study.

Bleeding and thrombosis are major complications associated with high mortality in extracorporeal membrane oxygenation (ECMO) management. Anticoagulant therapy should be adequate to reduce thrombosis. However, related studies are limited. We retrospectively reviewed all patients supported with ECMO at a single institution between January 2014 and July 2022 and included those on all types of ECMO using the Permanent Life Support System. Patients were classified into two groups according to their measured mean activated partial thromboplastin time (aPTT) during ECMO management: a high-anticoagulation (AC) group (aPTT, ≥55 seconds; n=52) and a low-AC group (aPTT, <55 seconds; n=79). The primary outcome was thrombotic or bleeding events during ECMO. We identified 10 patients with bleeding; significantly more of these patients were in the high-AC group (n=8) than in the low-AC group (15.4% vs. 2.5%, p=0.01). However, thrombus events and oxygenator change-free times were not significantly different between the two groups. Four patients in the high-AC group died of bleeding complications (brain hemorrhage, two; hemopericardium, one; and gastrointestinal bleeding, one). One patient in the low-AC group developed a thrombus and died of ECMO dysfunction due to circuit thrombosis. Heparin did not significantly improve thrombotic outcomes. However, maintaining an aPTT of ≥55 seconds was a significant risk factor for bleeding events, especially those associated with mortality.

Intravenous enoxaparin as alternative ECMO anticoagulation over a period of 94 days: a case report

BackgroundUnfractionated heparin is used worldwide as a standard anticoagulation therapy for extracorporeal membrane oxygenation (ECMO) machines. However, its use brings about significant bleeding and thrombotic complications for critically ill patients. This case report shows that low molecular weight heparin together with ECMO-produced primary haemostasis pathology can be used as an alternative way of ECMO anticoagulation.Case presentationThis paper presents the case of a patient with respiratory failure who subsequently suffered from cardiac failure and spent 94 days on combined V-V and V-A ECMO devices (two ECMO devices running simultaneously on one patient) with intravenous enoxaparin used instead of unfractionated heparin anticoagulation. No life-threatening bleeding/thrombotic events happened during this period, nor did any technical problems with ECMO occur.ConclusionsIn this case report, continuous intravenous low molecular weight heparin anticoagulation was used as a safe alternative to ECMO anticoagulation.

Editor’s Choice Articles for April

Editor’s Choice Articles for April

Superiority of bivalirudin over heparin anticoagulation therapy for extracorporeal membrane oxygenation? Too early to draw conclusions

BackgroundWe aimed to compare the efficacy and safety of bivalirudin versus heparin as the anticoagulant in patients undergoing extracorporeal membrane oxygenation (ECMO). MethodsWe conducted a search in PubMed, Embase and the Cochrane Library for all the studies in which bivalirudin was compared to heparin as the anticoagulant for ECMO. Efficacy outcomes were defined as the time to reach therapeutic levels, time within therapeutic range (TTR), thrombotic events, circuit thrombosis, circuit exchanges. Safety outcomes were reported as heparin-induced thrombocytopenia (HIT), major bleeding events, minor bleeding events. Other outcomes included hospital length of stay (LOS), ICU LOS, mortality, 30-day mortality and in-hospital mortality. ResultsTen studies with 1091 patients were included for meta-analysis. A significant reduction in thrombotic events [OR 0.51, 95%CI 0.36,0.73, p = 0.0002, I2 = 0%], major bleeding events [OR 0.31, 95%CI 0.10,0.92, p = 0.04, I2 = 75%] and in-hospital mortality [OR 0.63, 95%CI 0.44,0.89, p = 0.009, I2 = 0%] treated with bivalirudin were found compared with heparin. There were no significant differences between groups regarding the time to reach therapeutic levels [MD 3.53, 95%CI −4.02,11.09, p = 0.36, I2 = 49%], TTR [MD 8.64, 95%CI −1.72,18.65, p = 0.10, I2 = 77%], circuit exchanges [OR 0.92, 95%CI 0.27,3.12, p = 0.90, I2 = 38%], HIT [OR 0.25, 95%CI 0.02,2.52, p = 0.24, I2 = 0%], minor bleeding events [OR 0.93, 95%CI 0.38,2.29, p = 0.87, I2 = 0%], hospital LOS [MD −2.93, 95%CI -9.01,3.15, p = 0.34, I2 = 45%], ICU LOS [MD −4.22, 95%CI -10.07,1.62, p = 0.16, I2 = 0%], mortality [OR 1.84, 95%CI 0.58,5.85, p = 0.30, I2 = 60%] and 30-day mortality [OR 0.75, 95%CI 0.38,1.48, p = 0.41, I2 = 0%]. ConclusionBivalirudin probably be a potential choice for ECMO anticoagulation. However, based on the included studies’ limitation, the superiority of bivalirudin over heparin for anticoagulation in the ECMO population still require further prospective randomized controlled studies before a definite conclusion.

132: ANTI THE ANTICOAGULATION IN ECMO? A SURVEY OF PRACTICES IN ADULT ECMO PATIENTS

Introduction: Two of the major risks associated with extracorporeal membrane oxygenation (ECMO) are bleeding and thromboembolism. Due to concerns for thrombosis, particularly of the circuit and oxygenator, the Extracorporeal Life Support Organization (ELSO) recommends that ECMO patients be systemically anticoagulated. However, several recent trials have called into question the preferred anticoagulant with direct thrombin inhibitors (DTIs) potentially supplanting unfractionated heparin (UFH) due to their more favorable pharmacokinetic profile and potential superiority. There is also increasing evidence in VV ECMO to suggest lower therapeutic ranges, or even no anticoagulation, are safe and effective strategies. The purpose of this survey was to assess and describe anticoagulation prescribing patterns at adult ECMO centers. Methods: An electronic survey was distributed to respondents through the ELSO newsletter and discussion board. The primary objective was to identify the primary anticoagulant utilized by respondent institutions. Secondary objectives included identifying anticoagulation monitoring methods, rationale for switching from UFH, and VV ECMO anticoagulation practices. Institutional demographics, standard anticoagulant and monitoring method, rationale for switching from UFH, and anticoagulation practices in VV ECMO patients were all assessed. Results: Eighteen centers completed the survey, with 17 of the 18 (94%) being ELSO designated centers. Most respondents (67%) were pharmacists at their respective institutions. UFH was identified as the primary anticoagulant at most centers (78%) with activated partial thromboplastin time (aPTT) (64%) and anti-Xa (21%) being the most common monitoring methods. The main reason for switching from UFH to a DTI was heparin-induced thrombocytopenia (HIT) (93%). There was variability with regards to anticoagulation practices for VV ECMO patients with 44% of centers anticoagulating all patients, 39% anticoagulating depending on patient specific factors, and 17% not anticoagulating at all. Conclusions: While UFH remains the anticoagulant of choice at most centers despite recent evidence, variability still exists with monitoring methods and anticoagulation practices for VV ECMO patients. Further research is necessary to standardize anticoagulation practices.

Reduced Intracranial Hemorrhage with Anticoagulation Guideline Implementation.

Hemorrhagic and thrombotic complications, including intracranial hemorrhage, embolic stroke, surgical bleeding, and circuit thrombosis, are common during extracorporeal membrane oxygenation (ECMO), occurring in up to 50% of patients. These complications have a significant impact on morbidity and mortality. Our objective was to implement standardized ECMO anticoagulation guidelines for the pediatric cardiothoracic intensive care unit (CTICU) to reduce the incidence of intracranial hemorrhage while on ECMO. All CTICU patients who received ECMO from January 2016 to December 2020 were retrospectively reviewed. Standardized ECMO anticoagulation guidelines were implemented in the fourth quarter of 2017. Variables and clinical outcomes before and after guideline implementation were compared. From January 2016 to December 2017, there were 22 separate ECMO runs. Eight of 22 (36%) suffered intracranial hemorrhage while on ECMO. Seven of 8 (88%) were withdrawn from ECMO secondary to bleed and expired prior to hospital discharge. From January 2018 to December 2020, there were 22 separate ECMO runs in the CTICU. Three of 22 (14%) suffered intracranial hemorrhage while on ECMO. One of 3 (33%) expired prior to hospital discharge. Implementation of standardized ECMO anticoagulation guidelines in the CTICU was successful in improving clinical outcomes as evidenced by reduction in the incidence of intracranial hemorrhage in this high-risk patient population.

Reduced Intracranial Hemorrhage with Anticoagulation Guideline Implementation

Hemorrhagic and thrombotic complications, including intracranial hemorrhage, embolic stroke, surgical bleeding, and circuit thrombosis, are common during extracorporeal membrane oxygenation (ECMO), occurring in up to 50% of patients. These complications have a significant impact on morbidity and mortality. Our objective was to implement standardized ECMO anticoagulation guidelines for the pediatric cardiothoracic intensive care unit (CTICU) to reduce the incidence of intracranial hemorrhage while on ECMO. All CTICU patients who received ECMO from January 2016 to December 2020 were retrospectively reviewed. Standardized ECMO anticoagulation guidelines were implemented in the fourth quarter of 2017. Variables and clinical outcomes before and after guideline implementation were compared. From January 2016 to December 2017, there were 22 separate ECMO runs. Eight of 22 (36%) suffered intracranial hemorrhage while on ECMO. Seven of 8 (88%) were withdrawn from ECMO secondary to bleed and expired prior to hospital discharge. From January 2018 to December 2020, there were 22 separate ECMO runs in the CTICU. Three of 22 (14%) suffered intracranial hemorrhage while on ECMO. One of 3 (33%) expired prior to hospital discharge. Implementation of standardized ECMO anticoagulation guidelines in the CTICU was successful in improving clinical outcomes as evidenced by reduction in the incidence of intracranial hemorrhage in this high-risk patient population.

Poor Reliability of Common Measures of Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation.

Anticoagulation management in pediatric extracorporeal membrane oxygenation (ECMO) is challenging with multiple laboratory measures utilized across institutions without consensus guidelines. These include partial thromboplastin time (PTT), thromboelastography (TEG), and antifactor Xa (aXa). We aimed to evaluate the consistency of TEG R-time, PTT, and aXa correlation to bivalirudin and heparin dosing. We conducted a single-center restrospective review of pediatric ECMO cases from 2018 to 2020 anticoagulated with bivalirudin or heparin. We collected up to 14 serial simultaneous TEG R-time, PTT, and aXa measurements over a 7 day ECMO course with corresponding bivalirudin or heparin dosing. We analyzed the correlation between bivalirudin, heparin, and the three measurements of anticoagulation. A total of 67 ECMO runs, 32 bivalirudin, and 35 heparin, and more than 1,500 laboratory values, of which >80% simultaneous, were analyzed. When assessing correlations at the individual patient level, there was no consistent correlation between dosing and at least one laboratory parameter in the majority of patients. Furthermore, 44% of the bivalirudin cohort and 37% of the heparin cohort exhibited no correlation with any parameters. There were statistically significant correlations only between bivalirudin and heparin dosing and the sum total of the different laboratory tests. These inconsistencies highlight the importance of multimodality testing of anticoagulation in the management of pediatric ECMO anticoagulation and cannot be relied on in isolation from bedside clinical judgment.

The Year in Extracorporeal Membrane Oxygenation: Selected Highlights From 2021

This review summarizes the extracorporeal membrane oxygenation (ECMO) or extracorporeal life support literature published in 2021. This Selected Highlights article is not intended to be an exhaustive review of the literature, but rather a summarizing of key themes that developed in the ECMO literature during 2021. The primary topics presented include the following: ECMO for coronavirus disease 2019, extracorporeal cardiopulmonary resuscitation, periprocedural cardiopulmonary support with ECMO, and anticoagulation for ECMO.

Extracorporeal membrane oxygenator as a bridge to heart–liver en bloc transplant in a patient with Fontan circulation

Extracorporeal membrane oxygenator as a bridge to heart–liver en bloc transplant in a patient with Fontan circulation

2021 ELSO Adult and Pediatric Anticoagulation Guidelines.

These guidelines for adult and pediatric anticoagulation for extracorporeal membrane oxygenation are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing ECLS / ECMO and describe what are believed to be useful and safe practice for extracorporeal life support (ECLS, ECMO) but these are not necessarily consensus recommendations. The aim of clinical guidelines are to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

Prevalence and Clinical Impact of Reduced Coagulation Factor XII Activity in Patients Receiving Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation provides large surface exposure to human blood leading to coagulation activation. Only limited clinical data are available on contact activation and coagulation factor XII activity in extracorporeal membrane oxygenation patients. Prospective cohort study. Three medical ICUs at the Medical University of Vienna. Adult patients receiving venovenous or venoarterial extracorporeal membrane oxygenation. None. The primary outcome was the change in coagulation factor XII activity in response to extracorporeal membrane oxygenation. Secondary outcomes included the prevalence of reduced coagulation factor XII activity (< 60%) among patients receiving extracorporeal membrane oxygenation and association of coagulation factor XII activity with thromboembolic and bleeding complications. An exploratory endpoint was the association of coagulation factor XII activity and activated partial thromboplastin time in heparinase-treated samples in vitro. Fifty-one patients with a total of 117 samples were included in the study between July 2018 and February 2020. Fifty patients (98%) had reduced coagulation factor XII activity at any timepoint during extracorporeal membrane oxygenation. Median coagulation factor XII activity during extracorporeal membrane oxygenation treatment was 30% (interquartile range, 21.5-41%) and increased after discontinuation (p = 0.047). Patients with thromboembolic complications had higher median coagulation factor XII activity during extracorporeal membrane oxygenation (34% vs 23%; p = 0.023). The odds of a thromboembolic event increased by 200% per tertile of median coagulation factor XII activity (crude odds ratio, 3.034; 95% CI, 1.21-7.63). No association with bleeding was observed. In heparinase-treated samples, coagulation factor XII activity correlated well with activated partial thromboplastin time (r = -0.789; p = 0.007). We observed a high prevalence of reduced coagulation factor XII activity in adult patients on extracorporeal membrane oxygenation, which may confound activated partial thromboplastin time measurements and limit its clinical usefulness for monitoring and titrating anticoagulation with unfractionated heparin. Lower coagulation factor XII activity was associated with less thromboembolic complications, which may highlight the potential of coagulation factor XII to serve as a target for anticoagulation in extracorporeal membrane oxygenation.

Establishment and evaluation of a rat model of extracorporeal membrane oxygenation (ECMO) thrombosis using a 3D-printed mock-oxygenator

BackgroundExtracorporeal membrane oxygenation (ECMO) research using large animals requires a significant amount of resources, slowing down the development of new means of ECMO anticoagulation. Therefore, this study developed and evaluated a new rat ECMO model using a 3D-printed mock-oxygenator.MethodsThe circuit consisted of tubing, a 3D-printed mock-oxygenator, and a roller pump. The mock-oxygenator was designed to simulate the geometry and blood flow patterns of the fiber bundle in full-scale oxygenators but with a low (2.5 mL) priming volume. Rats were placed on arteriovenous ECMO at a 1.9 mL/min flow rate at two different heparin doses (n = 3 each): low (15 IU/kg/h for eight hours) versus high (50 IU/kg/h for one hour followed by 25 IU/kg/h for seven hours). The experiment continued for eight hours or until the mock-oxygenator failed. The mock-oxygenator was considered to have failed when its blood flow resistance reached three times its baseline resistance.ResultsDuring ECMO, rats maintained near-normal mean arterial pressure and arterial blood gases with minimal hemodilution. The mock-oxygenator thrombus weight was significantly different (p < 0.05) between the low (0.02 ± 0.006 g) and high (0.003 ± 0.001 g) heparin delivery groups, and blood flow resistance was also larger in the low anticoagulation group.ConclusionsThis model is a simple, inexpensive system for investigating new anticoagulation agents for ECMO and provides low and high levels of anticoagulation that can serve as control groups for future studies.

Analysis of Viscoelastic Testing in Pediatric Patients Using the Pediatric Extracorporeal Membrane Oxygenation Outcomes Registry.

Use of viscoelastic tests (VETs), including thromboelastography (TEG) and rotational thromboelastometry (ROTEM), is increasing in the management of anticoagulation in extracorporeal membrane oxygenation (ECMO) patients. A retrospective review of data on 265 pediatric (<20 years old) ECMO patients who underwent VET and were submitted to the Pediatric ECMO Outcomes Registry (PEDECOR) was conducted to describe common coagulopathies in patients who underwent VET; associations between the VET parameters and traditional tests of coagulation; and comparisons in blood product usage in patients who underwent VET with those who did not. We calculated patient-level summary statistics and assessed differences between the groups using χ2 tests (categorical variables) and Kruskal-Wallis and Wilcoxon rank-sum tests (continuous variables). Viscoelastic test was utilized in 77% of patients in the analysis. Platelet dysfunction was the most common abnormality identified by TEG (30.8%) and ROTEM (9.7%). Bleeding patients who had VET performed received more cryoprecipitate transfusions than those who did not have VET (VET median = 9.7 ml/kg; interquartile range (IQR) = 4.3-22.0 ml/kg vs. no VET median = 5.1 ml/kg; IQR = 0-10.4 ml/kg; p = 0.0013). Given the growing use of VET in pediatric ECMO patients, further studies evaluating VET in managing complications as well as aiding in titration of anticoagulation therapy are needed.