Hemolytic and thrombocytopathic characteristics of extracorporeal membrane oxygenation systems at simulated flow rate for neonates*

Objective Changes in technology and increased reports of successful extracorporeal life support (ECLS) use in patient populations such as influenza, cardiac arrest and adults are leading to expansion of ECLS. Major limitations to ECLS expansion remain bleeding and thrombosis. These complications are the most frequent causes of death and morbidity. As a pilot project to provide baseline data for a detailed evaluation of bleeding and thrombosis in the current era, ECLS patients were analyzed from eight centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN). Study design Retrospective analysis of patients (<19 years) reported to the ELSO (Extracorporeal Life Support Organization registry from eight CPCCRN centers between 2005 and 2011. Subjects The study cohort consisted of 2036 patients [13% with congenital diaphragmatic hernia (CDH)]. Interventions none Main results In the cohort of non-CDH patients (n=1773), bleeding occurred in 38% of patients while thrombosis was noted in 31%. Bleeding and thrombosis were associated with a decreased survival by 40% (RR: 0.59; 95%CI: 0.53, 0.66) and 33% (OR 0.67; 95%CI: 0.60, 0.74). Longer duration of ECLS and use of venoarterial cannulation were also associated with increased risk of bleeding and/or thrombotic complications and lower survival. The most common bleeding events included surgical site bleeding (17%; n=306), cannulation site bleeding (14%; n=256), and intracranial hemorrhage (11%; n=192). Common thrombotic events were clots in the circuit (15%; n=274) and the oxygenator (12%; n=212), and hemolysis (plasma free hemoglobin>50 mg/dL) (10%; n=177). Among patients with CDH, bleeding and thrombosis occurred in, respectively, 45% (n=118) and 60% (n=159), Bleeding events were associated with reduced survival (RR 0.62; 95%CI: 0.46, 0.86) although thrombotic events were not (RR 0.92; 95%CI: 0.67, 1.26). Conclusions Bleeding and thrombosis remain common complications in patients undergoing ECLS. Further research to reduce or eliminate bleeding and thrombosis is indicated to help improve patient outcome.

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“…Successful implementation of such a process within ECLS will open the door for similar efforts throughout critical care medicine. (30, 31)…”

Section: Discussionmentioning

confidence: 99%

Association of Bleeding and Thrombosis With Outcome in Extracorporeal Life Support*

Dalton

Garcia-Filion

Holubkov

et al. 2015

Pediatric Critical Care Medicine

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“…Comorbid conditions were quantified with the Charlson Index [26]. While on ECMO, hepatic dysfunction was assessed by daily Liver SOFA scores [27, 28], and renal dysfunction was assessed either as acute kidney injury that was defined as 1.5 fold increase in creatinine [29], or the by the use of renal replacement therapy.…”

Section: Methodsmentioning

confidence: 99%

Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: a cohort study

et al. 2016

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Purpose The association between extracorporeal membrane oxygenation (ECMO) use and the development of thrombocytopenia is widely presumed yet weakly demonstrated. We hypothesized that longer duration of ECMO support would be independently associated with worsened thrombocytopenia. Methods We performed a single-center retrospective cohort study of 100 adults who received ECMO for acute respiratory failure. We used generalized estimating equations to test the association between days on ECMO and daily percentage of platelets compared to the first post-cannulation platelet count. We constructed a multivariable logistic regression model with backwards stepwise elimination to identify clinical predictors of severe thrombocytopenia (≤ 50,000/μL) while on ECMO. Results Days on ECMO was not associated with a decrease in platelet count in the unadjusted analysis (β: -0.85, 95% CI: -2.05 to 0.36), nor after controlling for days hospitalized prior to ECMO, APACHE II score, platelet transfusions, and potential thrombocytopenia-inducing medications (β: -0.85, 95% CI: -1.9 to 0.22). Twenty-two subjects (22%) developed severe thrombocytopenia. The APACHE II score and platelet count at the time of cannulation predicted the development of severe thrombocytopenia. The odds of developing severe thrombocytopenia increased 35% for every 5-point increase in APACHE II score (OR 1.35, 95% CI: 0.94 to 1.94), and increased 35% for every 25,000/μL platelets below a mean at cannulation of 188,000/μL (OR 1.35, 95% CI: 1.10 to 1.64). Conclusions Duration of ECMO is not associated with the development of thrombocytopenia. The severity of critical illness and platelet count at the time of cannulation predict the development of severe thrombocytopenia while receiving ECMO for respiratory failure. Future studies should validate these findings, especially in cohorts with more venoarterial ECMO patients, and should characterize the association between thrombocytopenia and bleeding events while on ECMO.

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“…8,9 Previous work by this lab documented no difference in hemolysis or platelet aggregation in an in vitro neonatal ECMO model, using several different combinations of neonatal pumps and oxygenators. 10 Moreover, therapies directed toward the inhibition of shear-induced platelet activation have not changed the incidence of thrombus formation.…”

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confidence: 99%

Platelet-Derived Microparticles Generated by Neonatal Extracorporeal Membrane Oxygenation Systems

et al. 2015

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Current anticoagulation strategies do not eliminate thromboembolic stroke or limb loss during neonatal extracorporeal membrane oxygenation (ECMO), a form of cardiopulmonary bypass (CPB). In adults, CPB surgery generates prothrombotic platelet-derived microparticles (PMPs), submicron membrane vesicles released from activated platelets. However, information on PMP generation in neonatal ECMO systems is lacking. The objective of this study was to compare PMP generation in five different neonatal ECMO systems, using a simulated circuit with swine blood at 300 ml/min for 4 hours. Systems were composed of both newer components (centrifugal pump and hollow-fiber oxygenator) and traditional components (roller-head pump and silicone membrane oxygenator). Free plasma hemoglobin levels were measured as an indicator of hemolysis and flow cytometry-measured PMP. Hemolysis generated in all ECMO systems was similar to that observed in noncirculated static blood (p = 0.48). There was no difference in net PMP levels between different oxygenators with a given pump. In contrast, net PMP generation in ECMO systems with a centrifugal pump was at least 2.5 times greater than in roller-head pump systems. This was significant when using either a hollow-fiber (p < 0.005) or a silicone membrane (p < 0.05) oxygenator. Future studies are needed to define the relationship between pump-generated PMP and thrombosis.

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Hemolytic and thrombocytopathic characteristics of extracorporeal membrane oxygenation systems at simulated flow rate for neonates*

Cited by 51 publications

References 37 publications

Association of Bleeding and Thrombosis With Outcome in Extracorporeal Life Support*

Association of Bleeding and Thrombosis With Outcome in Extracorporeal Life Support*

Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: a cohort study

Platelet-Derived Microparticles Generated by Neonatal Extracorporeal Membrane Oxygenation Systems

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